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[Title] A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia.

BACKGROUND: Among patients with B-cell chronic lymphoid leukemia, those with 13q14 deletion have a favorable outcome.

However, whether the percentage of cells with 13q- influences the prognosis or the biological characteristics of this disease is unknown.

We analyzed the clinico-biological characteristics and outcome of patients with B-cell chronic lymphoid leukemia with loss of 13q as the sole cytogenetic aberration.

DESIGN AND METHODS: Three hundred and fifty patients with B-cell chronic lymphoid leukemia were studied.

RESULTS: In 109 out of the 350 cases (31.1%) loss of 13q was the sole cytogenetic aberration at diagnosis.

In the subgroup of patients with 80% or more of cells with loss of 13q (18 cases), the overall survival was 56 months compared with not reached in the 91 cases in whom less than 80% of cells had loss of 13q (p< 0.0001).

CONCLUSIONS: Patients with B-cell chronic lymphoid leukemia with a high number of losses in 13q14 as the sole cytogenetic aberration at diagnosis display different clinical and biological features: short overall survival and time to first therapy as well as more proliferation and less apoptosis.

A quantification of the number of cells showing a genetic abnormality should, therefore, be included in the study of the prognostic factors of B-cell chronic lymphoid leukemia.

[MeSH-major] Chromosome Deletion. Chromosomes, Human, Pair 13 / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / genetics

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(PMID = 19252174.001).

[ISSN] 1592-8721

[Journal-full-title] Haematologica

[ISO-abbreviation] Haematologica

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Italy

[Other-IDs] NLM/ PMC2649343

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness.

A PRoliferation-Inducing TNF Ligand (APRIL) costimulates B-cell activation.

When overexpressed in mice, APRIL induces B-cell neoplasia, reminiscent of human B-cell chronic lymphoid leukemia (B-CLL).

We analyzed APRIL expression in situ in human non-Hodgkin lymphomas.

APRIL up-regulation was only observed in high-grade B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL).

Hence, APRIL produced by inflammatory cells infiltrating lymphoma lesions may increase tumor aggressiveness and affect disease outcome.

[MeSH-major] Burkitt Lymphoma / metabolism. Lymphoma, B-Cell / metabolism. Lymphoma, Large B-Cell, Diffuse / metabolism. Lymphoma, Non-Hodgkin / metabolism. Neoplasm Proteins / physiology. Neutrophils / metabolism. Proteoglycans / metabolism. Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology

[MeSH-minor] B-Cell Maturation Antigen / metabolism. Gene Expression Regulation, Neoplastic. Humans. Kaplan-Meier Estimate. Neoplasm Invasiveness. Prognosis. Protein Structure, Tertiary. Retrospective Studies. Survival Analysis. Transmembrane Activator and CAML Interactor Protein / metabolism. Up-Regulation

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[ErratumIn] Blood. 2007 Sep 1;110(5):1474

(PMID = 17190854.001).

[ISSN] 0006-4971

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

[Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / B-Cell Maturation Antigen; 0 / Neoplasm Proteins; 0 / Proteoglycans; 0 / TNFRSF13B protein, human; 0 / TNFRSF17 protein, human; 0 / TNFSF13 protein, human; 0 / Transmembrane Activator and CAML Interactor Protein; 0 / Tumor Necrosis Factor Ligand Superfamily Member 13

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Paraneoplastic leukocytoclastic vasculitis in chronic lymphoid leukemia.

A 50-year-old female who was a known case of chronic lymphoid leukemia (CLL) developed ecchymoses, purpuric spots with papules, some nodules (1-3 mm) and crusts all over the body associated with severe burning and itching along with exaggeration of CLL.

[MeSH-major] Lymphoma, Non-Hodgkin / complications. Paraneoplastic Syndromes / etiology. Vasculitis, Leukocytoclastic, Cutaneous / etiology

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(PMID = 17998707.001).

[ISSN] 1998-4138

[Journal-full-title] Journal of cancer research and therapeutics

[ISO-abbreviation] J Cancer Res Ther

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] India

[Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Antineoplastic Agents, Hormonal; 18D0SL7309 / Chlorambucil; 9PHQ9Y1OLM / Prednisolone

   

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Multiple lymphomatous polyposis associated with small lymphocytic lymphoma: a unique presentation.

Multiple lymphomatous polyposis (MLP) is a rare extra-nodal manifestation of lymphoma.

In most cases, MLP is associated with mantle cell lymphoma (MCL).

We report a 66-year-old male diagnosed with small lymphocytic lymphoma (SLL)/chronic lymphocytic lymphoma (CLL), who showed evidence of rectal bleeding.

A colonoscopy revealed the presence of multiple polypoid lesions, biopsies of which showed diffuse lymphoid infiltrate without any identifiable follicles.

Immunohistochemical analysis combined with a Fluorescence In-Situ Hybridization (FISH) study excluded the diagnosis of MCL.

A bone marrow aspiration biopsy demonstrated diffuse infiltration of the bone marrow with low grade lymphocytes that expressed CD 20, CD5 and CD23, with negative BCL-1, t (11;.

A diagnosis of B-cell CLL with kappa light chain restriction was made.

The patient's bone marrow revealed a B-cell lymphoma of CLL/SLL phenotype, which to our knowledge has not been linked to MLP in previously reported cases.

[MeSH-major] Colonic Polyps / diagnosis. Colorectal Neoplasms / diagnosis. Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis. Lymphoma, Mantle-Cell / diagnosis

[MeSH-minor] Aged. B-Lymphocytes / metabolism. Biomarkers, Tumor / metabolism. Bone Marrow / pathology. Diagnosis, Differential. Humans. Male

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(PMID = 19104711.001).

[ISSN] 1841-8724

[Journal-full-title] Journal of gastrointestinal and liver diseases : JGLD

[ISO-abbreviation] J Gastrointestin Liver Dis

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Romania

[Chemical-registry-number] 0 / Biomarkers, Tumor

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Initial diagnosis of small lymphocytic lymphoma in parotidectomy for Warthin tumour, a rare collision tumour.

Warthin tumours (WT) and malignant lymphomas are only rarely associated, and most are examples of involvement of the lymphoid stroma of WT by a disseminated lymphoma.

This report describes a case where excision of a parotid mass led to the initial diagnosis of WT and small lymphocytic lymphoma (SLL).

The diagnosis of SLL was confirmed by immunohistochemistry and molecular studies.

The patient had stage IV A disease and is currently in chemotherapy induced complete remission.

This case highlights the extremely rare association of SLL with WT and the importance of evaluation of the WT stroma, where the pale proliferation centres of SLL may mimic germinal centres of reactive lymphoid nodules.

[MeSH-major] Adenolymphoma / pathology. Leukemia, Lymphocytic, Chronic, B-Cell / pathology. Neoplasms, Multiple Primary / pathology. Parotid Neoplasms / pathology

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(PMID = 15735173.001).

[ISSN] 0021-9746

[Journal-full-title] Journal of clinical pathology

[ISO-abbreviation] J. Clin. Pathol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] England

[Other-IDs] NLM/ PMC1770608

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Modifying akt signaling in B-cell chronic lymphocytic leukemia cells.

Emerging evidence suggests that the survival of B-cell chronic lymphocytic leukemia (CLL) cells is dependent on microenvironmental influences such as antigenic stimulation and support by stromal cells.

We investigated the role of Akt and its modulation by the protooncogene T-cell leukemia 1a (Tcl1a) in the survival pathways of primary CLL samples and CLL-derived prolymphocytic cell lines MEC-1 and MEC-2.

Akt activation was increased by the protective presence of human bone marrow stromal cells and B-cell receptor mimicking signals but antagonized by direct Akt blockade with the novel specific inhibitor AiX, with preferential apoptosis induction in CLL cells with an unmutated immunoglobulin status, which predicts poor clinical outcome.

Confirming the critical role of Tcl1a in modulating Akt signaling, Akt activation was enhanced by overexpressing Tcl1a in CLL.

In contrast, decreasing Tcl1a levels by small interfering RNA reduced Akt activation in the fludarabine-insensitive CLL cell line MEC-2 and sensitized the malignant cells to fludarabine treatment.

In summary, our data reveal a significant role for the Akt-Tcl1a axis in CLL survival and propose a further evaluation of this interplay for targeting chemoresistance phenomena.

[MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / enzymology. Proto-Oncogene Proteins / metabolism. Proto-Oncogene Proteins c-akt / metabolism

[MeSH-minor] Apoptosis / drug effects. Cell Line, Tumor. Enzyme Inhibitors / pharmacology. Humans. Oxazines / pharmacology. RNA, Small Interfering / genetics. Signal Transduction. Transfection

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[Copyright] ©2010 AACR.

(PMID = 20823161.001).

[ISSN] 1538-7445

[Journal-full-title] Cancer research

[ISO-abbreviation] Cancer Res.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Enzyme Inhibitors; 0 / Oxazines; 0 / Proto-Oncogene Proteins; 0 / RNA, Small Interfering; 0 / TCL1A protein, human; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Analysis of immunophenotype, lymphocytic subsets and NK cells in patients with B cell chronic lymphoid leukemia].

The aim of this study was to evaluate the values of immunophenotype of leukemic cells in bone marrow (BM) or peripheral blood (PB), lymphocytic subsets and NK cells of PB in diagnosis, therapy and prognosis of patients with B cell chronic lymphoid leukemia (B-CLL).

The samples of PB and BM from 67 patients with B-CLL were collected and detected by multi-parameter flow cytometry.

The results showed that the percentage of lymphocytes in PB of 67 patients with B-CLL obviously increased, as compared with normal persons, while CD3, CD4, CD8 and NK cells decreased significantly (p < 0.01), and no CD4/CD8 ratio had notable change (p > 0.05).

In their immunophenotype results, the positive expression rate of CD19 was highest (91.04%), followed by CD5 (80.60%), CD 20 (76.12), cyCD 79a (74.63%), CD 38 (43.28%), CD 11c (42.86%), CD 7 (41.94%), ZAP-70 (39.29%), CD25 (0.00%); co-expression rate of CD5 and CD19 was 72.73%; the expression of ZAP-70 was correlated with CD 38 (p < 0.05).

In conclusion, detection of cell immunophenotypes, lymphocytic subsets in PB and BM and NK cells in PB contribute to diagnosis of patients with B-CLL.

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(PMID = 19236743.001).

[ISSN] 1009-2137

[Journal-full-title] Zhongguo shi yan xue ye xue za zhi

[ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi

[Language] CHI

[Publication-type] English Abstract; Journal Article

[Publication-country] China

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: Although hematopoietic cell gene therapy using retroviral vectors has recently achieved success in clinical trials, safety issues regarding vector insertional mutagenesis have emerged.

Vector insertion, resulting in transcriptional activation of proto-oncogenes, played a role in the development of lymphoid leukemia in an X-linked severe combined immunodeficiency trial, and caused myeloid clonal dominance in a trial for chronic granulomatous disease.

These events have raised the question of whether gene therapy for other disorders such as β-thalassemia and sickle cell disease may hold a similar risk.

This rate was higher than that observed for a lentiviral vector containing a viral long-terminal repeat (LTR).

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[Copyright] Copyright © 2008 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

(PMID = 28178501.001).

[ISSN] 1525-0024

[Journal-full-title] Molecular therapy : the journal of the American Society of Gene Therapy

[ISO-abbreviation] Mol. Ther.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Alemtuzumab shows promise for CLL.

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(PMID = 28581422.001).

[ISSN] 1474-5488

[Journal-full-title] The Lancet. Oncology

[ISO-abbreviation] Lancet Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Defects in programmed cell death or apoptosis are major hallmarks of cancer contributing to tumorigenesis, tumor progression, and therapy resistance.

In the past decade, many of the pathways leading to apoptosis, as well as the molecular mechanisms blocking the death of tumor cells, have been elucidated.

Strategies include activation of proapoptotic mediators such as death receptors, tumor protein p53, and second mitochondria-derived activator of caspases (SMAC)/DIABLO as well as inhibition of endogenous apoptosis inhibitors such as IAPs (inhibitor of apoptosis proteins) and BCL-2 (B-cell chronic lymphoid leukemia/lymphoma) proteins.

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(PMID = 17896835.001).

[ISSN] 1173-8804

[Journal-full-title] BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

[ISO-abbreviation] BioDrugs

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review

[Publication-country] New Zealand

[Chemical-registry-number] 0 / Anticarcinogenic Agents; 0 / TNF-Related Apoptosis-Inducing Ligand

[Number-of-references] 145

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Thalidomide-induced partial stable remission in a case of refractory progressive B Cell Chronic Lymphoid Leukemia.

[MeSH-major] Leukemia, B-Cell / drug therapy. Thalidomide / therapeutic use

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(PMID = 17544506.001).

[ISSN] 0145-2126

[Journal-full-title] Leukemia research

[ISO-abbreviation] Leuk. Res.

[Language] eng

[Publication-type] Case Reports; Letter

[Publication-country] England

[Chemical-registry-number] 4Z8R6ORS6L / Thalidomide

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The antiapoptotic protein Api5 and its partner, high molecular weight FGF2, are up-regulated in B cell chronic lymphoid leukemia.

[MeSH-major] Apoptosis Regulatory Proteins / metabolism. Fibroblast Growth Factor 2 / metabolism. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism. Nuclear Proteins / metabolism. Up-Regulation

[MeSH-minor] Cell Line, Tumor. Humans. Molecular Weight

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(PMID = 17827341.001).

[ISSN] 0741-5400

[Journal-full-title] Journal of leukocyte biology

[ISO-abbreviation] J. Leukoc. Biol.

[Language] eng

[Publication-type] Letter; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / API5 protein, human; 0 / Apoptosis Regulatory Proteins; 0 / Nuclear Proteins; 103107-01-3 / Fibroblast Growth Factor 2

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology.

The 2001 World Health Organization classification scheme considers B-cell chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in an aggregate category (CLL/SLL) because of shared clinicopathological features.

We have estimated age-adjusted incidence rates (IRs) of CLL and SLL in the population-based Surveillance, Epidemiology and End Results Program in the United States to analyse patterns of CLL and SLL separately and jointly.

Age-standardized to the 2000 US population, overall IRs were 3.83 per 100 000 person-years for CLL (n = 15 676) and 1.31 for SLL (n = 5382) during 1993-2004.

Incidence of the combined entity, CLL/SLL, was 90% higher among males compared to females, and the male:female IR ratio was significantly higher for CLL (1.98) than for SLL (1.67).

CLL/SLL IRs were 25% and 77% lower among Blacks and Asian/Pacific Islanders, respectively, compared to Whites.

A significant reporting delay was evident for CLL but not for SLL, so that CLL/SLL temporal trends must be interpreted cautiously.

CLL and SLL IRs increased exponentially with age among all gender/race groups, with CLL IRs increasing more steeply with advancing age than SLL.

[MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / epidemiology

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(PMID = 17941952.001).

[ISSN] 1365-2141

[Journal-full-title] British journal of haematology

[ISO-abbreviation] Br. J. Haematol.

[Language] eng

[Grant] United States / Intramural NIH HHS / /

[Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Intramural

[Publication-country] England

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Unexpected toxicity (UT) and opportunistic infections (OI) after rituximab-containing therapy for non-Hodgkin's lymphoma (NHL).

Pts received a median of 6 cycles (range 1 - 18) of R.

A total of 517 cycles of R were evaluable for OI or UT.

UT consisted of interstitial pneumonitis (IP) in 2 pts after 8 and 6 cycles of R-CHOP for diffuse large cell lymphoma (DLCL), a case of congestive heart failure (NYHA III°) after 6x R-CHOP + 2x R-M for follicular lymphoma (FL) and a case of grade 4 pancytopenia lasting for 22 days following 2x R-FC for chronic lymphocytic leukemia.

Congestive heart failure improved under appropriate therapy and the pt received 2 more cycles of R-M.

OI consisted of pneumocystis jirovecii pneumonia after 5x R-CHOP-14 for DLCL, Epstein-Barr-virus (EBV)-associated hepatitis after 5x R-CHOP-21 for relapsed FL and generalized herpes zoster following 6x R-bendamustine (RB) + 1x R-M for recurrent BALT-lymphoma.

Moreover, 2 pts were transferred to us for therapy of enterovirus-induced encephalitis after 6x R-CHOP-21 + 2x R-M for FL (n=1) and cerebral toxoplasmosis in a pt heavily pretreated with R-containing therapy for relapsed mantle cell lymphoma (n=1).

In selected cases reexposure of R may be feasible.

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(PMID = 27960975.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: 728 patients were enrolled in 2 prospective studies of the GeneSearch BLN Assay (Veridex LLC) for SLN metastases.

Quantitative cycle times (CT) for mammaglobin (MG) and CK19 were correlated with finding ≥4+LN on final pathology.

Median CT for MG was 29.1 (interquartile range (IQR): 24.7-39.0) in patients with <4 +LN vs. 21.4 (IQR: 18.5-26.8) in those with ≥4 +LN, p<0.001.

Median CT for CK19 was 23.7 (IQR: 20.9-28.2) in patients with <4 +LN vs. 19.6 (IQR: 17.8-20.7) in those with ≥4 +LN, p<0.001.

Tumor size ≥2cm, proportion of SLN+ >50%, MG CT <25.8 and CK19 <20.8 were correlated with ≥4 +LN on final pathology.

A simplified CPR was created with 1 point given if tumor size was ≥2cm, 1 point if MG CT <25.8 and 2 points if CK19 CT<20.8.

Of the 24 patients (20.9%) with 0 points, only 1 (4.2%) had ≥4 +LN; of the 12 patients (10.4%) with 3 points, 8 (66.7%) had ≥4 +LN on final pathology, p<0.001.

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(PMID = 27960684.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies.

The PI3K p110δ isoform is highly expressed in cells of hematopoietic origin and plays a key role in B cell maturation and function.

CAL-101 is a potent inhibitor of PI3K p110δ (IC<sub>50</sub>=65 nM) with 40 to 300-fold selectivity compared to other PI3K isoforms.

In vitro studies of 0.1 to 10 μM CAL-101 showed inhibition of pAKT expression and/or apoptotic effects against primary chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) cells and against a range of leukemia and lymphoma cell lines.

METHODS: In an ongoing phase 1 dose escalation study in sequential cohorts of 3 patients with relapsed/refractory CLL or select B-cell non-Hodgkin's lymphoma, CAL-101 is administered orally twice daily for 28 days per cycle.

No treatment-related adverse events greater than grade 1 have been seen, with 2 patients treated for >5 cycles.

Two of 6 patients attained partial response and 4 have stable disease.

Partial responses were observed after 2 cycles of 50 mg in a patient with mantle cell lymphoma with 6 prior therapies, and after 1 cycle of 100 mg in a patient with follicular lymphoma with 6 prior therapies, including autologous stem cell transplant.

Disease specific cohort expansion will occur at the maximally tolerated dose, and patients with AML will be added.

CONCLUSIONS: Early results from a phase 1 study of the oral PI3K p110δ inhibitor CAL-101 show that it is well tolerated and has preliminary clinical activity in patients with B-cell malignancies.

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(PMID = 27961357.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Phase I/II study of oxaliplatin, fludarabine, cytarabine, and rituximab in patients (OFAR2) with Richter's syndrome (RS), and relapsed or refractory B-cell chronic lymphocytic leukemia (CLL).

: 7031 Background: The first Phase I-II clinical trial of oxaliplatin, fluradabine, Ara-C, and rituximab (OFAR1) demonstrated significant activity in refractory CLL and RS (Tsimberidou et al, J Clin Oncol, 2008;26:196).

To enhance the response rate with a decrease in myelosuppression, the dose of oxaliplatin was increased to 30 mg daily, the dose of Ara-C was decreased to 0.5g/m<sup>2</sup> daily and the optimal number of days of fluradabine and Ara-C administration was explored (OFAR2).

METHODS: The OFAR2 regimen consisted of oxaliplatin 30mg/m<sup>2</sup>, D1-4; fludarabine 30mg/m<sup>2</sup>, Ara-C 0.5 g/m<sup>2</sup>; rituximab 375mg/m<sup>2</sup>, D3; and pelfigrastim 6mg D6.

Forty-three pts were treated in the Phase II portion of the study (relapsed CLL, 35; RS, 8).

The median age was 64 yrs (range, 40- 81); 50 (91%) had β2-microglobulin > 3 mg/L; platelets were < 100 x10<sup>9</sup>/L in 22 pts; and 44 pts had > 1 prior therapies.

Eleven pts underwent stem cell transplantation as postremission or salvage therapy.

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(PMID = 27961393.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Subcutaneous injections of low doses of veltuzumab (humanized anti-CD20 antibody): Objective responses in B-cell malignancies.

: 8530 Background: Low IV doses of veltuzumab, a second-generation anti-CD20 monoclonal antibody with structure-function differences from chimeric rituximab, have shown clinical activity, thus justifying subcutaneous (SC) injections.

METHODS: A phase I/II study was initiated in patients (pts) with previously untreated or relapsed CD20+ indolent NHL or CLL who received 4 SC injections of veltuzumab 2 weeks apart at dose levels of 80, 160, or 320 mg.

Efficacy was assessed by CT-based IWG (NHL) or hematology-based NCI/IWCLL (CLL) criteria 4 and 12 weeks later, with responding pts continuing follow-up.

Other evaluations included AEs, safety laboratories, B-cell blood levels (CD19), serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers.

RESULTS: Nineteen pts (8M/11F, median age 63), including 14 NHL pts (11 follicular, 3 other indolent NHL; 5 treatment naive) most with stage III or IV disease (11/14) and 5 CLL pts (4 treatment naïve) all with Rai stage II or III disease, have now received SC veltuzumab at 80 mg (3 NHL, 3 CLL), 160 mg (9 NHL, 2 CLL) or 320 mg (2 NHL) dose levels.

Pre-treatment with antihistamines or steroids has not been required, and SC veltuzumab was well tolerated with only mild, transient injection site reactions and tenderness.

In NHL pts, SC veltuzumab demonstrates good bio-availability, with a slow release pattern over several days and depletion of circulating B cells starting after 1<sup>st</sup> injection.

For 7 NHL pts, 4 weeks after treatment with 80 or 160 mg doses, 2 pts had partial responses, 3 pts showed stable disease, and 2 pts had disease progression.

For 3 CLL pts who received 80 mg doses, serum veltuzumab levels were lower, but all pts still achieved 65-75% decreases in circulating leukemic cells over the course of treatment.

CONCLUSIONS: SC administration of veltuzumab is well tolerated, achieves slow but efficient delivery into the blood, and is pharmacologically active.

The low doses currently evaluated in B-cell malignancies show evidence of therapeutic activity, achieving objective responses in NHL and notable reductions in circulating leukemic cells in CLL.

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(PMID = 27960927.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Extramedullary Leukemic Relapses Following Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning.

Of a group of 149 patients who underwent allogeneic stem cell transplantation using the "Mexican approach," a nonablative preparative regimen, 49 individuals developed bone marrow relapse, and 8 patients developed extramedullary relapse (EMR).

In contrast, bone marrow relapses presented in patients with myeloid or lymphoid malignancies.

When EMR was noted, acute graft-versus-host disease (GVHD) had presented in 4 patients, and limited forms of chronic GVHD were present in 3 patients.

The only individual alive 240 days after relapse shows no evidence of a full-blown hematologic relapse.

An EMR after allogeneic hematopoietic stem cell transplantation usually has a bad prognosis and presents mainly in individuals with high-risk malignancies.

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(PMID = 28401517.001).

[ISSN] 1865-3774

[Journal-full-title] International journal of hematology

[ISO-abbreviation] Int. J. Hematol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] Japan

[Keywords] NOTNLM ; Allograft / Extramedullary / Leukemia / Nonmyeloablative / Relapse

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 3004 Background: The limited effect of cancer immunotherapy is due to the tumor's ability to induce host anergy towards its antigens.

The preclinical data support the activity of 1-MT in preventing T-cell anergy in TDLN, slowing growth of LLC mouse xenografts, and synergizing with chemotherapy in regression of autochthonous breast tumors in MMTV-Neu mice.

Correlative studies include serum kyn/trp levels, T-reg cell quantification by flow, tumor IDO expression by IHC, and humoral immune response using a proprietary tumor antigen microarray.

Attributable toxicities were 1 case of grade 1 fatigue and 2 cases of grade 2 hypophysitis.

CONCLUSIONS: 1-MT appears to be an active, orally bioavailable, and reasonably well tolerated immunomodulator at 200mg daily.

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(PMID = 27962050.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The utility of a real-time RT-PCR assay for the detection of metastases greater than 0.2 mm in sentinel lymph nodes of breast cancer patients confirmed by detailed histological analysis.

Our study confirms the reliability of the cutoff values of a real-time RT-PCR assay (GeneSearch, Veridex LLC) to detect metastases larger than 0.2 mm by detailed 0.2 mm frozen section histological diagnosis.

One half of each LN was used for routine intra-operative diagnosis.

These sections were then re-stained immunohistochemically using a pancytokeratin antibody (AE1/AE3) for detecting submicrometastses.

Cutoff values were pre-set in a large US study (n = 304).

RESULTS: Compared to the histological diagnosis using 0.2 mm interval frozen sections, the real-time RT-PCR results were as follows; sensitivity of 100.0% (34/34), specificity of 93.7% (89/95), and overall accuracy of 95.3% (123/129).

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(PMID = 27961430.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Ongoing phase I studies of ABT-263: Mitigating Bcl-X<sub>L</sub> induced thrombocytopenia with lead-in and continuous dosing.

Ongoing phase 1 studies of ABT-263 show anti-tumor activity in CLL and some lymphomas (Wilson W et al, ASH. 2008).

However, thrombocytopenia (TCP) due to on-target Bcl-X<sub>L</sub> inhibition-induced platelet apoptosis is also observed.

TCP was a dose limiting toxicity (DLT) in 3 patients (pts) in CLL study M06-873 (N = 15) where starting platelet counts tend to be low.

METHODS: CD with a 7 d lead-in dose was explored (150, 150 or 100 mg lead-in doses) with dosing at 200 and 275 mg, 225 and 325 mg, or 125 and 250 mg in studies M06-814 (NHL), M06-822 (SCLC), and M06 873 (CLL), respectively.

2 DLTs were observed for CD, 1 pt per study M06-814 (275 mg) and M06-873 (200 mg) experienced grade 4 (TCP).

While CD enrollment and time on study is still limited, anti-tumor activity includes 1 unconfirmed partial response (68% CT regression) in a SLL pt at 275 mg and 3 CLL pts with ≥50% lymphocyte reduction for ≥2 months.

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(PMID = 27961281.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Single-agent activity of GCS-100, a first-in-class galectin-3 antagonist, in elderly patients with relapsed chronic lymphocytic leukemia.

GCS-100 has been shown to induce apoptosis of patient CLL cells ex vivo.

In addition, GCS-100 potentiates the in vitro activity of other agents commonly used to treat CLL, including rituximab.

This phase II clinical trial evaluated the potential of GCS-100 as a novel single-agent therapeutic for relapsed CLL.

METHODS: Patients with Rai Stage II or higher CLL who had relapsed after one or two prior therapies were eligible.

Patients received GCS-100 i.v. at 160 mg/m<sup>2</sup> for 5 days every 21 days until disease progression.

GCS-100 was well-tolerated.

There were no cases of drug-related grade 3 or 4 hematological toxicity or other serious AE.

CONCLUSIONS: GCS-100 has significant single-agent activity in relapsed CLL.

Its lack of myelosuppression and potential synergy with other agents makes GCS-100 a strong candidate for further development in CLL, particularly for elderly patients for whom there is a major need for less toxic agents.

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(PMID = 27961378.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Trends in pneumonia (PNA) hospitalization among patients (pts) with chronic lymphocytic leukemia (CLL).

: e20500 Background: Despite recent therapeutic advances, PNA remains a significant source of morbidity and mortality among CLL pts.

Nationwide Inpatient Sample and ICD-9CM diagnosis codes, we identified all non-governmental hospitalizations of CLL pts for a primary dx of PNA in calendar years 1994 and 2004.

Admissions were described by pt demographics (age, gender, race) and comorbidity (Charlson index, presence of chronic lung disease).

Ten-year prevalence estimates for CLL were obtained from NCI SEER data and used as denominators in incidence calculations.

RESULTS: PNA was the primary dx for 7316 (13.1%) and 7651 (11.2%) CLL pt admissions in 1994 and 2004, respectively.

CLL pts admitted in 2004 were older (75.7 v. 74.2 years, p<0.001) and more likely to have at least one Charlson comorbidity (67.6% v. 56.2%, p<0.001) or comorbid chronic lung disease (40.6% v. 28.3%, p<0.001) than pts in 1994.

Intubation was rare in both cohorts (<1%) and did not significantly differ by year, but in-hospital mortality was significantly higher in 2004 (11.3% v. 8.2%, p=0.005).

However, LOS decreased significantly between 1994 and 2004 (9.2 v. 6.4 days, p<0.001).

CONCLUSIONS: PNA hospitalization rates for CLL pts have not significantly increased over the last decade despite more aggressive therapies, likely secondary to improved supportive care.

However, CLL pts hospitalized for PNA are now older, increasingly likely to suffer from chronic medical illness, and significantly more likely to die while in hospital.

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(PMID = 27960954.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Effect of CD37 small modular immuno-pharmaceutical (SMIP) on direct apoptosis in chronic lymphocytic leukemia cells via transcriptional up-regulation of the BH3 family member BIM.

A novel CD37<sup>SMIP</sup> was previously demonstrated to mediate superior direct apoptosis and NK-cell mediated killing of chronic lymphocytic leukemia (CLL) and other B-cell malignancies.

METHODS: Given the superior in vitro apoptosis observed with CD37<sup>SMIP</sup> treatment and early clinical activity observed in highly refractory CLL patients, we hypothesized that a unique mechanism of cell killing was utilized by CD37<sup>SMIP</sup>.

RESULTS: Unlike many other agents utilized to treat CLL, death mediated by CD37<sup>SMIP</sup> does not depend upon caspase activation.

Nonetheless, CD37<sup>SMIP</sup> treatment of CLL cells promotes time-dependent induction of mitochondrial membrane depolarization, mitochondrial translocation of Bax, and up-regulation of Bim protein.

CD37<sup>SMIP</sup> Bim protein induction occurred concomitantly with an increase in BIM mRNA levels.

Electrophoretic mobility shift assay using oligonucleotides of the BIM promoter demonstrated increased protein binding activity in nuclear extracts derived from CD37<sup>SMIP</sup> treated cells and the physical interaction of FoxO3a transcription factor with the FoxO3a responsive element in the BIM promoter was demonstrated using a "protein pull down" assay and confirmed by chromatin immunoprecipitation assays.

Furthermore, CD37<sup>SMIP</sup> treatment significantly increased BIM promoter regulated luciferase reporter expression in B-CLL cells.

Consistent with a primary role of Bim up-regulation in mitochondrial membrane destabilization and apoptosis, transfection of CLL cells with BIM siRNA resulted in inhibition of CD37<sup>SMIP</sup>-induced mitochondrial membrane depolarization and apoptosis.

CONCLUSIONS: These studies demonstrate CD37<sup>SMIP</sup> mediated apoptosis in CLL cells occurs via FoxO3a-dependent transcriptional up-regulation of BIM protein.

This distinct mechanism of apoptosis utilized by CD37<sup>SMIP</sup> contrasts it with other agents used for CLL treatment.

Additionally, it provides a mechanism for the promising clinical activity of TRU-016 (humanized CD37<sup>SMIP</sup>) observed to date in refractory CLL patients.

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(PMID = 27962079.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A phase II pilot study of valproic acid in relapsed/refractory chronic lymphocytic leukemia.

: 7081 Background: Valproic acid (VA) has demonstrated cell-kill by triggering pro-apoptotic pathways in chronic lymphocytic leukemia (CLL) in preclinical studies.

We studied the safety and efficacy of VA in patients with relapsed and refractory CLL.

METHODS: Adult patients with CLL diagnosed by the NCI-WG criteria who had received at least one previous fludarabine-based therapy and subsequently progressed or relapsed with ECOG performance status (PS) ≤3 and normal organ functions were included.

RESULTS: Five patients have so far been included, age 48-70 years (mean 62 years); sex: 3 males/ 2 females; disease duration: 2-16 years (mean 5.4 years).

One patient had partial response and one had stable disease.

Grade 3 hypersensitivity skin rashes developed in one patient at one month and the therapy was discontinued.

Most patients had mild drowsiness and two patients had significant weight gain of grade 2.

CONCLUSIONS: VA produces very impressive palliation in advanced/ refractory CLL in terms of improvement of hemoglobin, ANC, platelets, PS, and a reduction in the number of infective episodes -apparently a sequel to significant rise in neutrophils.

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(PMID = 27961474.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Long term follow-up of primary B and T cell non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract.

: e19516 Background: Anthracycline based chemotherapy is the treatment of choice for aggressive primary lymphomas of the GI tract, with surgery reserved for management of complications.

We report long term follow up of 71 cases of primary GI NHL treated with chemotherapy and/or surgery.

Median age at diagnosis was 60 (15-83).

52 (73%) were DLBCL, 11 (16%) were T-cell, 8 (11%) were MALT.

Of the aggressive lymphomas (63), all patients with T cell lymphoma had small bowel as primary site and histological evidence of celiac associated enteropathy, even in the absence of known celiac disease.

Primary sites of DLBCL were stomach 35 (67%), small bowel 11 (21%) & colon 6 (12%).

39 (62%) patients underwent surgery at diagnosis due to acute presentation with perforation, bleeding or obstruction, or to obtain histology.

Following confirmed diagnosis, 61 patients received anthracycline based chemotherapy.

2 patients with T cell lymphoma presented with perforation, were treated with surgery only and died of rapid disease progression.

Of the 63 patients with aggressive NHL, 37 (59%) remain alive & disease free at median follow up of 13 years (1-24).

35 (67%) patients with DLBCL are alive & disease free.

Only 2 (18%) of the T cell lymphomas are alive & disease free.

All deaths in the T cell group were due to progressive disease.

CONCLUSIONS: Patients with aggressive primary B cell GI NHL have almost 70 % survival following anthracycline based chemotherapy.

However, in contrast, coeliac enteropathy associated T-cell lymphomas present with rapidly progressive disease & have a survival of < 20% with chemotherapy and/or surgery.

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(PMID = 27960953.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A study of the prevalence and type of anemia in lymphoid malignancies.

: e19556 Background: Anemia is a common and serious problem in patients with lymphoid malignancy.

METHODS: Newly diagnosed patients of lymphoid malignancy- non Hodgkins lymphoma (NHL), Hodgkins lymphoma (HL), and chronic lymphocytic leukemia (CLL) aged more than 15 years without renal failure and who had not received blood transfusion, iron, folic acid or vitamin B complex in the last 2 weeks were analyzed.

Of the anemic patients (hemoglobin <11gm/dl), 46 were studied for the type of anemia.

Anemia was categorized as due to either autoimmune hemolytic anemia (AIHA)-DCT positive with evidence of hemolysis on PBS, B12 and folate deficiency (<200 pgm/ml and < 4ngm/ml respectively), iron deficiency anemia (IDA)- psat <20% and SF315μgm/dl, anemia of chronic disease (ACD)-psat200μgm/L, a combination of IDA and ACD -psat <20%, SF -30-200 with TIBC ≤315 μgm/dl.

RESULTS: The prevalence of anemia in patients with lymphoid malignancy was 42.41% (134 /316, 95% CI-36.96% -47.85%).

CONCLUSIONS: Although anemia of chronic disease is the most common cause of anemia in patients with lymphoid malignancy, it is multifactorial in a large number of patients and hence it is important to rule out other causes of anemia like nutritional and AIHA in these patients.

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(PMID = 27961090.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 621 Background: A RT-PCR Assay (GeneSearch, Veridex, LLC), FDA approved and CE marked to detect metastases > 0.2 mm in sentinel lymph nodes (SLNs) of breast cancer patients, has been in clinical use in our institute for 25 months.

An additional 74 patients were tested in a pilot study.

The marker Ct values are correlated with metastases size as determined by H&E on adjacent node pieces (r = -0.74 for MG and -0.77 for CK19, p < 0.001).

For example when CK19 and MG < 24 Cts, the non-SLN positivity rate jumps from 29% to 58%.

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(PMID = 27961419.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] ABT-263 activity and safety in patients with relapsed or refractory lymphoid malignancies in particular chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

: 8574 Background: ABT-263, a novel, orally bioavailable, BH3 mimetic, binds with high affinity (K<sub>i</sub> ≤ 1nM) and inhibits multiple antiapoptotic Bcl-2 family proteins.

ABT-263 displays activity (EC<sub>50</sub> ≤ 1μM) against human lymphoid and small cell lung cancer cell lines.

Mechanism based preclinical toxicities include reductions in circulating lymphocytes, apoptosis of circulating platelets, and decreased spermatogenesis, mediated by inhibition of Bcl-2, Bcl-X<sub>L</sub>, and Bcl-w, respectively.

METHODS: Safety and activity of ABT-263 in 2 enrolling phase I studies in relapsed/refractory lymphoid malignancies (M06-814) and CLL (M06-873) was evaluated.

Patients (pts) were dosed on days 1-14 of a 21 d cycle, 10-440mg (M06-814) or 10-250mg (M06-873).

Among 27 CLL/SLL pts, 3 have confirmed radiographic partial responses (PR) (99%, 92% and 72%) and 2 have unconfirmed regressions, 51% and 72%.

6 pts maintained a ≥50% decrease in circulating lymphocytes for ≥ 2 months and 11 pts have stable disease; of these 5 experienced minor radiographic responses (range of 36% to 49%).

In addition, among 40 (M06-814) lymphoma pts, 3 with follicular lymphoma achieved PR and one had a minor response (49% regression).

With CD dosing (16 pts), activity includes 1 unconfirmed PR in SLL & and 3 CLL pts with ≥50% lymphocyte reduction for ≥2 months duration.

Pharmacodynamic toxicities included dose-dependent thrombocytopenia (TCP) resulting from on-target activity against Bcl-X<sub>L</sub>.

Dose limiting toxicities, 14/21 d dosing, in M06-814 occurred at 160mg (bronchitis), 315mg (elevated ALT and grade 4 TCP) and 440mg (worsening pleural effusion in a pt with underlying afib), and in M06-873 at 110mg (tumor lysis and grade 4 TCP) and 250mg (grade 4 TCP).

CONCLUSIONS: ABT-263 showed favorable PK and safety profiles with anti-tumor activity in relapsed/refractory CLL/SLL and follicular lymphoma.

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(PMID = 27962273.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Evaluation of the effect of TRU-016, an anti-CD37 directed SMIP in combination with other therapeutic drugs in models of non-Hodgkin's lymphoma.

: 8571 Background: TRU-016, a single chain anti-CD37 Fc fusion molecule has been shown to display pro-apoptotic and Fc-dependent cellular cytotoxicity activities against primary CLL cells and NHL cell lines.

The pro-apoptotic signal generated by TRU-016 binding to CD37 on CLL cells has been shown to be caspase-independent and distinct from the signal generated by many other therapeutics including rituximab.

We have tested drug combinations using the mantle cell lymphoma line Rec-1 and diffuse large B-cell lymphoma line SU-DHL-6 in vitro and extended these results to in vivo settings using the follicular lymphoma cell line DOHH2 treated with the combination of TRU-016 and bendamustine.

METHODS: To determine TRU-016 interactions with the established therapeutics rituximab, doxorubicin, rapamycin, and bendamustine, drugs were tested alone or in combination with TRU-016 and the anti-proliferative effects on cell lines measured after 96 hours.

To determine if in vitro synergy could be recapitulated in vivo, SCID mice were implanted with DOHH2 cells and therapeutic treatment was initiated when tumor volumes reached 200 mm<sup>3</sup>.

This demonstrates that the in vitro synergy results were extendable to a more complex in vivo disease model.

CONCLUSIONS: TRU-016 in combination with rituximab, rapamycin, or bendamustine increases cell killing of NHL cells.

Furthermore, the combination of TRU-016 and bendamustine displayed greater in vivo anti-tumor activity than either agent alone against a follicular lymphoma tumor model.

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(PMID = 27961015.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] IKZF1 (IKAROS) deletions as a prognostic marker in BCR-ABL1 positive acute lymphoblastic leukemia patients: A GIMEMA ALL WP Report.

: 11005 Expression of BCR-ABL1 in hematopoietic stem cells can alone induce a chronic myeloid leukemia (CML) but cooperating oncogenic lesions are required for the generation of a blastic leukemia.

To identify oncogenic sub-microscopic lesions that cooperate with BCR-ABL1 to induce ALL, by high resolution single nucleotide polymorphism (SNP) arrays (250K NspI and SNP 6.0, Affymetrix) we studied 106 patients (pts) with de novo adult BCR-ABL1-positive ALL.

The most frequent somatic copy number alteration was deletion on 7p12 of IKZF1 (68/106, 64%), which encodes the transcription factor Ikaros required for the earliest stages of lymphoid lineage commitment.

Gene expression profiling analysis of pts with IKZF1 deletion vs wild-type pts identified a unique signature characterized by a down-regulation of genes involved in pre-B-cell differentiation (e.g.

VPREB1, VPREB3, IGLL3, BLK), demonstrating that genomic IKZF1 alterations have a strong impact on trascriptoma and contribute to an impaired B-cell differentiation.

Univariate analysis showed that the IKZF1 deletion is a negative prognostic marker influencing the cumulative incidence of relapse (10.1 months for pts with deletion vs 56.1 months for wild-type pts, p=0.0103) and disease-free survival (DFS) (10.1 months vs 32.1 months, respectively, p=0.0229).

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(PMID = 27964054.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 2580 Background: A phase I study of flavopiridol, a cyclin-dependent kinase inhibitor, using an alternative schedule was conducted in pts with solid tumors given its promising activity in pts with chronic lymphocytic leukemia (CLL).

DLT was defined as Gr 4 hematologic toxicity (HT) for > 7 days, > Gr 3 non-HT except Gr 3 fatigue or diarrhea resolving <4 days and cytokine release syndrome (CRS) > Gr 3 despite steroids.

Due to a grade 5 CRS/death in cohort 3, the protocol was amended to include 20 mg IV dexamethasone prior to flavopiridol to prevent CRS (cohorts 2B, 1B).

Of the 20 evaluable pts, 35% had stable- and 65% had progressive-disease.

CONCLUSIONS: There was a higher frequency of CRS, despite prophylactic steroids seen our pts with solid tumors compared to previous studies with CLL and this correlated with AUC.

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(PMID = 27961903.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Expression of different isoforms of the B-cell mutator activation-induced cytidine deaminase (AID) in BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients.

: 7049 Since the activation-induced cytidine deaminase (AID) enzyme can target non-immunoglobulin (Ig) genes and may even act as a genome-wide mutator, we investigated AID expression in BCR-ABL1-positive ALL and in chronic myeloid leukemia (CML) at the time of progression to blast crisis.

On the 61 de novo adult BCR-ABL1-positive ALL patients (pts), AID mRNA and protein were detected in 36 (59%); their expression correlated with BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors at the time of remission.

AID expression was also found in lymphoid blast crisis CML (50%), but not in myeloid lineage or in chronic phase CML.

Different isoforms of AID were identified: 13/61 (21%) pts expressed the full-length isoform; 19/61 (31%) co-expressed the wild-type and different AID splice variants with deaminase activity (AIDΔE4a, with a 30 bp deletion of exon 4; AIDΔE4, with the exon 4 deletion; AIDins3, with the retention of intron 3-4); 4/61 (7%) expressed the AIDΔE3-E4 isoform without deaminase activity (deletion of exons 2 and 3).

Patients who expressed wild-type AID had a higher number of alterations compared to AID-negative (median copy number alteration of 14 versus 4. respectively, p < 0.03).

Our findings show that BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that can act as mutator outside the Ig gene loci in promoting genetic instability in leukemia cells.

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(PMID = 27961429.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: We reviewed the English literature by conducting systematic MEDLINE using the terms TNF-, infliximab, adalimumab, etanercept, cancer therapy, hematologic malignancies, myelodysplastic syndrome (MDS), multiple myeloma (MM), myeloproliferative disease (MPD), chronic lymphocytic leukemia (CLL), and lymphoma from January 2001 to August 2008.

RESULTS: Overall 11 phase I and II studies (n = 237; CLL n = 44, MM n = 10, MDS n = 109, MPD n = 51, HCL n = 3, TCL 13, FL 7) that involved anti-TNF- therapy in hematological malignancies were identified.

In conjunction with ATG or azacitidine in low-/intermediate-risk MDS, TNF inhibitors resulted in improvement in cytopenia.

No significant clinical benefit was seen among lymphoproliferative disorders, but treatment was well tolerated.

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(PMID = 27961263.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

3 RCTs assessed the efficacy of early versus deferred treatment in prostate cancer, 3 in multiple myeloma, and 1 each in lung cancer and chronic lymphocytic leukemia (CLL).

There was no survival difference between early and deferred treatment in multiple myeloma (HR=1.11,95%CI 0.67-1.84), CLL (HR=0.89,95%CI 0.49-1.59) or lung cancer (HR=0.95,95%CI 0.72-1.24).

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(PMID = 27961594.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Inhibition by lenalidomide of growth factor and hypoxia-induced signaling in endothelial and epithelial tumor cells, and effects within the tumor cell microenvironment.

Lenalidomide studies in CLL and MM suggest that it may also attenuate pro-survival signals generated by interaction of stroma with the malignant cell itself.

Ovarian cancer cell lines SKOV-3 and OVCAR-3 were treated with LPA and the effect of lenalidomide on invasiveness via enhanced p-Akt was investigated.

Treatment of ovarian tumor cells with LPA increased tumor cell invasiveness via enhanced p-Akt.

Lenalidomide strongly inhibited invasion and p-Akt (at S308 but not T473) in a dose-dependent manner.

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(PMID = 27964203.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Activity of ofatumumab, a novel CD20 mAb, and prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia (CLL).

: 7044^ Background: Salvage therapy has limited activity (20-26% overall response rate [ORR]) in patients (pts) with CLL refractory to fludarabine and alemtuzumab (double-refractory, DR) or refractory to fludarabine with bulky (>5 cm) lymphadenopathy (bulky fludarabine-refractory, BFR).

Ofatumumab (OFA) is a fully human mAb that targets a unique small-loop epitope of CD20 close to the cell surface and elicits more potent in vitro complement-dependent cytotoxicity of B-cell lines and tumor cells vs rituximab (RTX).

To determine whether prior RTX exposure impacted activity of OFA in pts with DR or BFR CLL, an analysis was performed to assess efficacy by prior RTX exposure in pts treated with OFA in an international, pivotal study.

METHODS: Pts with DR or BFR CLL received 8 weekly infusions of OFA followed by 4 monthly infusions (Dose 1, 300 mg; Doses 2-12, 2,000 mg).

Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS).

Median PFS (95% CI) was 5.7 mo (4.5, 8.0) and 5.9 mo (4.9, 6.4), and median OS (95% CI) was 13.7 mo (9.4, NYR) and 15.4 mo (10.2, 20.2), respectively.

CONCLUSIONS: Single-agent therapy with OFA is effective in pts with DR or BFR CLL, irrespective of prior CD20 mAb therapy with RTX.

Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area;.

(2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research.

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(PMID = 27961407.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Phase I study of intranodal direct injection of adenovirus encoding recombinant CD40-ligand (Ad-ISF35) in patients with chronic lymphocytic leukemia.

: 3003 Background: Transduction of chronic lymphocytic leukemia (CLL) cells with replication-defective adenovirus (Ad) encoding a genetically engineered, membrane-stablized CD154 (ISF35) converts transduced, and "bystander" non-transduced, CLL cells into proficient antigen presenting cells that can induce immunity against autologous leukemia cells.

Preclinical studies demonstrated that direct injection of Ad-ISF35 into lymphoma nodules can induce potent anti-lymphoma immune responses in test animals, capable of eradicating lethal tumors at distal sites and protect against recurrent disease upon subsequent re-challenge with syngeneic tumor.

Pts, ages 45-71 yrs, with rapidly progressive disease (median CLL doubling time of 3.7 months) each received a single ultrasound guided IDI of 1 to 30 x 10<sup>10</sup> Ad-ISF35 viral particles in 4 different dose cohorts.

RESULTS: IDI of Ad-ISF35 was well-tolerated and effective in inducing systemic responses.

Some pts had grade ≤ 2 injection-site erythema, pain and/or swelling, or flu-like symptoms.

Some pts in the highest-dose cohorts had transient, asymptomatic grade 3/4 hypophosphatemia.

No long-term (≥ 6 wk) adverse effects were observed.

Although there was no evidence for dissemination of Ad-ISF35 beyond the injected lymph node, IDI of Ad-ISF35 induced blood CLL cells to express death receptors, pro-apoptotic proteins, and immune co-stimulatory molecules similar to those induced on "bystander" CLL cells co-cultured with Ad-ISF35 transduced cells in vitro.

Importantly, IDI of Ad-ISF35 resulted in significant reductions in blood leukemia cell counts and a median reduction of 53.2% (range 25-75.4%) in the size of lymph nodes and/or spleen, which was durable (≥ 4 months) in 9 pts.

Despite aggressive disease prior to treatment, the median treatment-free survival was 5.3 months and 3 pts have yet to require additional treatment after 1-year follow-up.

CONCLUSIONS: Single IDI of Ad-ISF35 was safe and effective in inducing systemic biologic and clinical responses in pts with CLL.

IDI of Ad-ISF35 might be effective in the treatment of CLL and related lymphomas.

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(PMID = 27962049.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Clinical improvement with a novel CD20 mAb, ofatumumab, in fludarabine-refractory chronic lymphocytic leukemia (CLL) also refractory to alemtuzumab or with bulky lymphadenopathy.

: 7043 Background: Patients (pts) with CLL refractory tofludarabine and alemtuzumab (double-refractory, DR) or refractory to fludarabine with bulky (>5 cm) lymphadenopathy (bulky fludarabine-refractory, BFR) have a poor prognosis.

Ofatumumab is a human mAb specific for a distinctive small-loop epitope of CD20 that appears more potent than rituximab in eliciting complement-dependent lysis of B cells in vitro.

We report, for the first time, results from the planned interim analysis of the clinical benefit observed in pts with DR or BFR CLL treated with ofatumumab in an international pivotal clinical study.

METHODS: Pts with DR or BFR CLL received 8 weekly then 4 monthly ofatumumab infusions (Dose 1, 300 mg; Doses 2-12, 2,000 mg).

RESULTS: Of 138 treated pts (DR: N = 59; BFR: N = 79; median age 64 and 62 yrs, respectively), 63% had Rai stage III/IV disease at screening.

Resolution of disease symptoms (maintained for ≥2 mo) were observed in a large proportion of pts (Table), including in pts considered nonresponders by NCI-WG criteria.

Pts with thrombocytopenia at baseline (n = 73) experienced sustained increases in median platelet counts from 65 × 10<sup>9</sup>/L to over 100 × 10<sup>9</sup>/L by Wk 8; a similar pattern of rapid improvement was observed in Hgb values.

CONCLUSIONS: Ofatumumab as single-agent achieves high ORR, and improves disease symptoms and hematologic parameters in heavily pretreated pts with DR and BFR disease who lack standard treatment options.

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(PMID = 27961406.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

METHODS: Seven NCCCP sites utilized the log during the 60 day open accrual period for the Wake Forrest WFU 07-02-03 cancer control trial (chronic lymphocytic leukemia COLD- fX) in Novermber 2008 and December 2008.

RESULTS: 327 chronic lymphocytic leukemia patients were screened mostly by chart review.

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(PMID = 27963861.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Guillain-Barre Syndrome Associated with Gastric Cancer: Paraneoplastic Syndrome or Immunological Disorder?

Paraneoplastic Guillain-Barre syndrome has been described in association with some kinds of tumors (B-cell Lymphoma and small cell lung cancer).

We describe the case of a 74-year-old woman affected by gastric adenocarcinoma, treated with surgery and adjuvant chemotherapy, who developed simultaneously skin cancer relapse and severe Guillain-Barre syndrome.

Although the timing of clinical presentation suggests a paraneoplastic origin, other interesting features were present in this patient such as familial and personal anamnesis for autoimmune disease, HCV infection, and neurotoxic chemotherapy.

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(PMID = 29147216.001).

[ISSN] 1920-454X

[Journal-full-title] World journal of oncology

[ISO-abbreviation] World J Oncol

[Language] eng

[Publication-type] Journal Article

[Publication-country] Canada

[Keywords] NOTNLM ; Gastric cancer / Guillain Barre syndrome / Paraneoplastic syndrome

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] VSV Oncolysis in Combination With the BCL-2 Inhibitor Obatoclax Overcomes Apoptosis Resistance in Chronic Lymphocytic Leukemia.

In chronic lymphocytic leukemia (CLL), overexpression of antiapoptotic B-cell leukemia/lymphoma 2 (BCL-2) family members contributes to leukemogenesis by interfering with apoptosis; BCL-2 expression also impairs vesicular stomatitis virus (VSV)-mediated oncolysis of primary CLL cells.

In the effort to reverse resistance to VSV-mediated oncolysis, we combined VSV with obatoclax (GX15-070)'a small-molecule BCL-2 inhibitor currently in phase 2 clinical trials'and examined the molecular mechanisms governing the in vitro and in vivo antitumor efficiency of combining the two agents.

In combination with VSV, obatoclax synergistically induced cell death in primary CLL samples and reduced tumor growth in severe combined immunodeficient (SCID) mice-bearing A20 lymphoma tumors.

Combination treatment triggered the release of BAX from BCL-2 and myeloid cell leukemia-1 (MCL-1) from BAK, whereas VSV infection induced NOXA expression and increased the formation of a novel BAX-NOXA heterodimer.

These studies offer insight into the synergy between small-molecule BCL-2 inhibitors such as obatoclax and VSV as a combination strategy to overcome apoptosis resistance in CLL.

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[Copyright] Copyright © 2010 The American Society of Gene & Cell Therapy. Published by Elsevier Inc. All rights reserved.

(PMID = 28160637.001).

[ISSN] 1525-0024

[Journal-full-title] Molecular therapy : the journal of the American Society of Gene Therapy

[ISO-abbreviation] Mol. Ther.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Cytogenetic abnormalities in mesenchymal stem cells in chronic lymphocytic leukemia (CLL) patients and normal subjects.

: e22002 Background: Mesenchymal stem cells (MSC) residing in the marrow support hematopoiesis and protect cancer cells from undergoing cell death induced by chemotherapy.

Recent reports have described clonal cytogenetic abnormalities in the MSC of acute myeloid leukemia and myelodysplastic syndrome patients.

To determine if cytogenetic abnormalities are present in MSC from CLL patients, we analyzed karyotypes of MSC from 13 CLL patients and 5 normal subjects.

METHODS: Stromal cells from marrow core biopsies of 13 CLL patients and 5 normal control subjects were isolated, cultured and confirmed as MSC based on their immunophenotype and capacity to differentiate into three lineages.

After 3-4 non-stimulated cell culture passages, the karyotype was analyzed in 5-40 metaphase cells from each subject Abnormalities were considered clonal using the accepted convention of the same chromosomal gain or rearrangement in 2 or more cells or loss in at least 3 cells.

For each CLL patient, interphase FISH analysis to detect the common CLL-associated abnormalities was performed on freshly isolated peripheral blood mononuclear cells (PBMC).

RESULTS: Clonal cytogenetic abnormalities of the cultured MSC were observed in 6 of 13 CLL patients (46%) and 3 of 5 control subjects (60%).

The 6 CLL MSC had different clonal abnormalities than the PBMC CLL FISH studies.

One CLL MSC exhibited trisomy 5, one exhibited trisomy 8, and one had monosomy X clone.

There was no correlation of the chromosomal abnormalities in CLL MSC with clinical stage.

CONCLUSIONS: Marrow MSC derived from CLL patients and normal subjects do show an array of cytogenetic abnormalities including clonal chromosomal abnormalities.

However the genetic abnormalities found in both CLL and normal MSC could represent acquired genomic instability associated with advanced age, rather than oncogenesis associated with CLL.

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(PMID = 27963169.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Rasburicase (R), a recombinant urate oxidase, results in a more rapid and total reduction of uric acid (UA) compared to allopurinol (A) in children at high-risk of TLS (Goldman/Cairo et al, Blood.

METHODS: We convened an international panel (N = 17) of experts in pediatric and adult hematological malignancies and solid tumors (ST) to develop a medical decision tree for the P and T of TLS based on the risk classification (low, medium, high) and management recommendations of Coiffier et al (J Clin Oncol.

2008) Results: Patients without evidence of LTLS were assigned to either low-risk disease (LRD), medium-risk (MRD), or high-risk (HRD).

Risk factors included pathological classification stage, bulk, disease burden (WBC/LDH) and renal impairment/involvement.

HRD was assigned to patients with either B-ALL, ALL/AML ≥100K/mm<sup>3</sup>, BL/LL stage III/IV, and/or high LDH, DLBCL/PTCL/MCL/ATL with bulky and elevated LDH and patients with MRD with renal impairment/involvement.

MRD consisted of ALL ≤100K/mm<sup>3</sup>, AML 25-100K/mm<sup>3</sup>, BL/LL stage I/II and low LDH, childhood ALCL, DLBCL/PTCL/MCL/ATL non-bulky but elevated LDH, CLL treated with targeted therapy, and LRD with renal impairment/involvement.

LRD consisted of ST (except bulky sensitive to cytotoxic therapy [MRD]), CML, MM, HL, other NHL and AML <25K/mm<sup>3</sup>.

CONCLUSIONS: This medical decision tree will facilitate the practice of management of the P and T of TLS and hopefully improve the quality of care in a cost effective manner.

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(PMID = 27963935.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Clinical trial of NPI-0052 in advanced malignancies including lymphoma and leukemia (advanced malignancies arm).

Preclinical research suggests improvements in therapeutic ratio and activity in hematologic and solid tumor models, leading to clinical trials in patients with myeloma, lymphomas, leukemias, and solid tumors.

METHODS: Patients with solid tumor, lymphoma or leukemia diagnoses without standard treatment options were treated with IV NPI on Days 1, 8 and 15 of 28-day cycles in a 3+3 design dose escalation to a Recommended Phase 2 Dose (RP2D).

Enrollment then began in 10 patient lymphoma and CLL RP2D cohorts.

RESULTS: 30 patients were treated at doses ranging from 0.1 mg/m<sup>2</sup> to 0.9 mg/m<sup>2</sup>.

0.7 mg/m<sup>2</sup> was selected as the RP2D secondary to DLT of transient "hallucinations" (visual imprints when eyes closed) and dizziness/unsteady gait at 0.9 mg/m<sup>2</sup>.

At the RP2D PK data showed: half-life = 31 ± 28 min; AUC<sub>total</sub> = 270 ± 219 ng/mL*min; Cmax = 33.4 ± 34.2 ng/mL; clearance = 7.17 ± 0.40 L/min; volume of distribution (Vz) = 223.3 ± 229.7 L.

Stable disease was induced in 31% of patients, including one each with mantle cell, Hodgkin's lymphoma, follicular lymphoma, sarcoma, prostate carcinoma, and two with melanoma.

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(PMID = 27961753.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e13506 Background: SJG-136 is a pyrrolobenzodiazepine dimer that forms covalent DNA crosslinks in a sequence-specific manner in the minor groove.

A phase I study in patients (pts) with solid tumors revealed clinical activity, defined MTD as 30 mg/m<sup>2</sup>/d administered on daily x 3 schedule, and confirmed manageable toxicity.

Here we report the results of a CTEP-sponsored phase I trial of SJG-136 administered on a daily x 5 schedule in pts with relapsed or refractory (R/R) leukemias.

METHODS: Previously treated pts with R/R acute leukemias (AML, ALL, high risk MDS, CML blast phase) or R/R CLL with adequate organ function and ECOG performance status of ≤ 2 were eligible for the study.

The starting dose level was 6 mcg/m<sup>2</sup> given intravenously daily x 5 days on a 21 day cycle.

Pts were sequentially enrolled in cohorts of 3 and the dose was escalated in a classic 3+3 schema at the dose levels: 6, 12, 24, and 36 mcg/m<sup>2</sup>.

Pts enrolled at each dose level (mcg/m<sup>2</sup>) were: 6 (3 pts), 12 (5 pts), 24 (4 pts), 36 (4 pts).

The dose of 36 mcg/m<sup>2</sup> was found to be above the MTD, with the DLT being grade 3 soft tissue edema.

Other manifestations of vascular leak including grade I, II hypoalbuminemia, edema, and pleural effusions were seen in a number of patients starting at dose level 24 mcg/m<sup>2</sup> and above.

One pt had a PR, 8 pts had stable disease, and 6 had progression.

CONCLUSIONS: SJG-136 is safe and active in patients with advanced leukemias.

24 mcg/m<sup>2</sup> is the recommended phase II dose for the daily x 5 schedule.

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(PMID = 27961262.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Phase I/II study of a hybrid schedule of flavopiridol in relapsed/refractory mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).

However, a pharmacologically derived hybrid schedule of administration is effective in refractory, genetically high-risk CLL, though life-threatening tumor lysis syndrome (TLS) may occur in patients with very high lymphocyte counts.

Because flavopiridol decreases cyclin D1 and mcl-1 and induces apoptosis in MCL cells, is significantly toxic for cell lines derived from the activated B-cell-like type of DLBCL (OCI-Ly3) and down-regulates NF-kappa B, we investigated the hybrid schedule in MCL and DLBCL.

Other toxicities were grade 4 ANC (10 pts) requiring prophylactic G-CSF, TLS (1 pt) and bowel perforation (1 pt).

Analysis of cell cycle and transcriptional cdk targets is ongoing.

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(PMID = 27961020.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A phase I trial of TRU-016, an anti-CD37 small modular immunopharmaceutical (SMIP) in relapsed and refractory CLL.

Pre-clinical studies have demonstrated CD37 SMIP mediates significantly greater direct and NK-cell mediated killing of CLL cells as compared to other therapeutic antibodies used in CLL.

METHODS: Patients with relapsed/refractory CLL or SLL who had adequate organ function, platelets > 30,000/mm<sup>3</sup> were eligible.

Dose escalation and de-escalation is based on CTC AE toxicity grades.

Mild (grade 1-2) infusion toxicity has been observed in 3 patients.

Two patients had partial clearing of leukemia cutis, and the other six had 27-94% reduction in peripheral lymphocyte count.

CONCLUSIONS: To date, TRU-016 is a well tolerated treatment with minimal infusional toxicity and no observed dose limiting toxicity.

Encouraging reduction in tumor lymphocyte blood counts, lymph node/spleen size and improvement in normal hematopoeitic function in patients with high risk genomic CLL have already been observed at low, non-saturating doses of CD37.

Future single agent and combination studies of Tru16 in CLL are warranted.

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(PMID = 27962057.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Efficacy of lenalidomide oral monotherapy in relapsed or refractory indolent non-Hodgkin's lymphoma: Final results of NHL-001.

: 8560 Background: Lenalidomide has shown activity in a wide range of hematological malignancies.

We conducted a phase II trial of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).

Oral lenalidomide 25 mg was self-administered once-daily on days 1-21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression.

The ORR was 23% (10/43), including a complete response (CR) or unconfirmed CR (CRu) rate of 7%.

The median time to first response was 3.6 months (1.7-4.2) and the median time to CR or CRu was 4.2 months (1.9-11.1).

Twenty-seven percent (6/22) of patients with follicular lymphoma grade 1 or 2, and 22% (4/18) of patients with small lymphocytic lymphoma responded to therapy.

Adverse events were consistent with the known safety profile of lenalidomide and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).

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(PMID = 27960983.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] JC papovavirus leukencephalopathy in a patient with B-CLL receiving long-term chemotherapy in combination with an anti-CD20-antibody.

METHODS: Our patient was a 64-year-old woman with B-CLL diagnosed in 2000 in state B of Binet treated with 12 cycles of fludarabin until July 2007 in a B-cell and lymphoma-reducing manner.

For the reason of progressive disease 3 cycles of rituximab, fludarabin, mitoxantrone, and cyclophosphamide were added (dose reduced causing hematologic toxicity) until October 2007 continuing rituximab once a month up to Mai 2008.

RESULTS: In a CT scan mixed response was observed with progressive disease infradiafragmatic and regression supradiafragmatic.

Corticosteroids could stop B-symptoms and leads to a distinct shrinkage of the lymphomas within 2 weeks.

An MRI of the brain showed subcortical and periventricular lesions with increased signal on T2-weighted and fluid attentuated inversion recovery (FLAIR) suggestive of a vascular origin.

Her symptoms progressed by aphasia and weakness of the right leg corresponding to increased size and number of cerebral lesions.

CONCLUSIONS: Antibody deficiency syndrome corresponding to CLL under treatment with chemotherapy and rituximab lead to a severe immunosuppression enabling unusual viral infections such as PML.

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(PMID = 27963992.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Ad-ISF35-transduced autologous cells promote in vitro and in vivo chemosensitization in patients with 17p-/P53-defective chronic lymphocytic leukemia.

: e14552 Background: Transduction of chronic lymphocytic leukemia (CLL) cells with a replication-defective adenovirus (Ad) encoding recombinant CD154 (Ad-ISF35) induces expression of death receptors and Bid via a P53-independent pathway involving induction of P73.

Induction of P73 significantly enhances the sensitivity of P53-defective CLL cells to "P53-dependent" drugs, such as Fludarabine (F-ara-A).

Patients with P53-defective CLL who received iv infusions of autologous Ad-ISF35-transduced CLL cells were observed to achieve complete remissions (CR) with subsequent treatment using F-ara-A based treatment regimens, suggesting Ad-ISF35 could sensitize P53-defective CLL to chemotherapy.

METHODS: We examined patients with drug-resistant and/or P53-defective CLL before and after iv infusions of autologous Ad-ISF35-transduced CLL cells who were enrolled in a phase I study examining whether such treatment could sensitize patients to a truncated fludarabine, cyclophosphamide and rituximab (FCR) regimen.

We examined CLL cells for sensitivity to F-ara-A in vitro, expression of CD95, DR5, Bid, and P73 and correlated these with the response to treatment in vivo.

RESULTS: P53-defective CLL cells were resistant to F-ara-A induced apoptosis with IC50 > 10μM prior to treatment.

CLL cells collected from patients≥24 hours after IV infusion of autologous Ad-ISF35-trasduced CLL cells became sensitive to the cytotoxic effects of F-ara-A, with IC50 0.3-1 μM.

Enhanced sensitivity to F-ara-A was associated with induced expression of Bid, DR5, CD95, and P73 by circulating CLL cells, an effect lasting≥2 weeks following iv infusion.

Consistent with this, we observed complete resolution in lymphocytosis, lymphadenopathy and splenomegaly following 1 cycle of FCR administered 2 weeks after 3 biweekly infusions of Ad-ISF35- transduced CLL cells.

CONCLUSIONS: IV infusion of autologous Ad-ISF35-transduced CLL cells can induce de novo, systemic expression of death receptors and Bid on bystander CLL cells, which is associated with enhanced sensitivity of P53-defective CLL to the cytotoxic effects of standard chemotherapy [Table: see text].

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(PMID = 27963590.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The effects of sildenafil citrate on malignant B-cells in patients with chronic lymphocytic leukemia.

: 7076 Background: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western Hemisphere, with over 10,000 cases diagnosed annually in the United States.

It is characterized by progressive accumulation of functionally incompetent long-lived lymphocytes, shown to be secondary to a defect in programmed cell death or apoptosis.

The phosphodiesterase inhibitor sildenafil induces capsase dependent apoptosis of malignant B lymphocytes in vitro.

This study will test the hypothesis that sildenafil reduces the expression of BCL-2 and increases the spontaneous apoptosis rate of malignant B-cells in patients with CLL.

METHODS: Thirteen patients with Rai Stage 0 CLL were enrolled.

RESULTS: The median age of patients enrolled in the study was 74 with a median white blood cell count of 18 x10<sup>3</sup>/mL.

While one patient withdrew due to blehparitis, not felt to be a side effect of sildenafil, all other patients tolerated the medication well without any adverse effects.

There was no significant decrease in white blood cell count or Bcl-2 expression; capsase 3 activity and apoptosis rates remained undetectable on presentation and throughout treatment.

CONCLUSIONS: At a dose of 25 to 50 mg weekly, sildenafil does not appear to have any effects on the malignant B cells in CLL.

While this dose may not produce a measurable clinical or cellular response, higher doses may still have an effect on the malignant B cells of CLL.

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(PMID = 27961459.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Chronic lymphocytic leukemia (CLL) coexistent with HIV: An increasing association?

CLL is the most common leukemia in Western countries, yet very little has been published regarding HIV coexistent with CLL.

Therefore, the aim of this study was to evaluate the clinicopathological findings and outcome of HIV-associated CLL in a series of cases.

METHODS: Cases of HIV-associated CLL/small lymphocytic leukemia (SLL) were collected from the authors' archives and published case reports (using PubMed search).

Information regarding patient demographics (age, gender), mode of HIV acquisition, HAART use, immunosuppression (HIV Viral load [VL], CD4+ cell count), clinical presentation, pathology, and outcome were abstracted and analyzed.

Immunologic parameters available for 4 patients showed a median CD4+ count of 930 cells/mm3 (range, 396-1374) and mean HIV VL of 2,103 copies/ml (range, <75-5,297).

CLL/SLL was diagnosed by lymph node biopsy (n = 1) and/or flow cytometry (n = 5).

Two patients remained well without treatment and 4 required therapy due to either hemolytic anemia, CLL- induced renal failure, pancytopenia, or hypogammaglobulinemia with recurrent infections.

CONCLUSIONS: CLL/SLL may occur in association with HIV infection in the elderly without significant concomitant immunosuppression.

CLL-related complications in our small series were frequent (67%), including mortality (50%).

Additional cases of CLL/SLL are anticipated as HIV-infected patients in the HAART era are reported to be living longer.

The association between HIV and CLL is deserving of further attention and we encourage clinicians to report their findings.

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(PMID = 27961484.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Fine-needle aspiration biopsy findings in patients with small lymphocytic lymphoma transformed to hodgkin lymphoma.

Although small lymphocytic lymphoma (SLL) is an indolent lymphoma, approximately 5% of cases can transform to a higher-grade lymphoma, rarely Hodgkin lymphoma (HL).

We report the fine-needle aspiration (FNA) results of 6 cases of SLL/chronic lymphocytic leukemia (CLL) that transformed to HL.

The patients included 5 men and 1 woman, ranging in age from 49 to 72 years at the time of SLL/CLL diagnosis with time for development of HL ranging from 0 to 95 months (mean, 49.3 months).

The FNA diagnoses were SLL with HL transformation (2 cases), SLL with large atypical cells (1 case), and atypical lymphoid proliferation with large atypical cells (3 cases).

Flow cytometry performed in 5 cases (2 FNA specimens) demonstrated a monoclonal B-cell population with CD19/CD5 coexpression.

The presence of large atypical mononucleated and binucleated cells in lymph node FNA specimens from patients with SLL/CLL with progressive adenopathy should raise the possibility of transformation to HL.

[MeSH-major] Cell Transformation, Neoplastic / pathology. Hodgkin Disease / pathology. Leukemia, Lymphocytic, Chronic, B-Cell / pathology

[MeSH-minor] Aged. Biopsy, Fine-Needle. Epstein-Barr Virus Infections / diagnosis. Epstein-Barr Virus Infections / virology. Female. Flow Cytometry. Herpesvirus 4, Human / genetics. Herpesvirus 4, Human / isolation & purification. Humans. Lymph Nodes / pathology. Male. Middle Aged. RNA, Viral / analysis

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(PMID = 17875507.001).

[ISSN] 0002-9173

[Journal-full-title] American journal of clinical pathology

[ISO-abbreviation] Am. J. Clin. Pathol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / RNA, Viral

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Polymorphism in the CD5 gene promoter in B-cell chronic lymphocytic leukemia and mantle cell lymphoma.

Despite the low incidence of microsatellite instability (MSI) in lymphoid malignant neoplasms, it has been reported that the CD5 promoter MSI was relatively frequent among B-cell chronic lymphoproliferative disorders.

We studied the presence of MSI in the CD5 promoter in 134 cases of B-cell chronic lymphocytic leukemia (B-CLL) and 47 of mantle cell lymphoma (MCL) by comparing the pattern of microsatellite repeats on autologous germline and tumor DNA samples.

However, the allele distribution of this polymorphism showed a higher frequency of the 18 CA allele (0.585) in MCL cases (P = .026; odds ratio [OR], 1.75; 95% confidence interval [CI], 1.07-2.87) and of the 19 CA allele (0.179) in B-CLL cases (P = .005; OR, 2.26; 95% CI, 1.27-4.01) compared with control cases (0.442 and 0.087, respectively).

This suggests that although MSI seems not to be involved in the pathogenesis of these 2 lymphoid malignant neoplasms, the polymorphic CD5 promoter is associated with increased susceptibility to these disorders.

[MeSH-major] Antigens, CD5 / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / genetics. Lymphoma, Mantle-Cell / genetics. Polymorphism, Genetic. Promoter Regions, Genetic

[MeSH-minor] DNA, Neoplasm / analysis. Gene Frequency. Genetic Predisposition to Disease. Humans. Microsatellite Repeats / genetics. Odds Ratio

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(PMID = 15981803.001).

[ISSN] 0002-9173

[Journal-full-title] American journal of clinical pathology

[ISO-abbreviation] Am. J. Clin. Pathol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Antigens, CD5; 0 / DNA, Neoplasm

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Association of squamous cell carcinoma of the larynx and chronic lymphoid leukemia.

INTRODUCTION: The association of squamous cell carcinoma of the larynx and chronic lymphocytic leukemia (CLL) is exceptional.

We report an observation of this association and present the therapeutic problems as well as the effects on prognosis.

OBSERVATION: Direct laryngoscopy showed a tumor of the right hemilarynx, with the biopsy concluding in moderately differentiated keratinizing squamous cell carcinoma.

The anatomopathological examination of the operative specimen demonstrated infiltration of the larynx and squamous cell carcinoma adenopathies and CLL.

It was decided to monitor the chronic lymphoid leukemia, classified as Binet stage B.

The synchronous or metachronous onset of a second cancer in a patient with CLL is more frequent than in the general population.

The synchronous association of squamous cell carcinoma of the larynx and CLL has been described only rarely.

The prognosis is more negative in an association of cervicofacial squamous cell carcinoma and leukemia than in a single cervicofacial cancer.

[MeSH-major] Carcinoma, Squamous Cell. Laryngeal Neoplasms. Leukemia, Lymphoid. Neoplasms, Multiple Primary

[MeSH-minor] Aged. Chronic Disease. Humans. Male

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[Copyright] Copyright © 2010 Elsevier Masson SAS. All rights reserved.

(PMID = 20851364.001).

[ISSN] 1879-730X

[Journal-full-title] European annals of otorhinolaryngology, head and neck diseases

[ISO-abbreviation] Eur Ann Otorhinolaryngol Head Neck Dis

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] France

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] IGHV3-21 gene expression in patients with B-cell chronic lymphocytic leukemia in Ukraine.

THE AIM of the study was to evaluate the frequency of IGHV3-21 gene usage and its clinical significance for patients with B-cell chronic lymphocytic leukemia (CLL) in Ukraine.

PATIENTS AND METHODS: Immunoglobulin variable heavy chain (IGHV) gene repertoire was studied in 189 CLL patients using reverse transcribed polymerase chain reaction and direct sequence of amplified products.

RESULTS: IGHV3-21 gene expression was found in 11 cases (5.8%), and its frequency was intermediate between Scandinavian (11.7%) and Mediterranean CLL (2.9%) cohorts.

The differences in overall (OS), progression-free (PFS) and treatment-free survival (TFS) for IGHV3-21 positive patients in comparison with CLL patients expressing the other IGHV genes were statistically insignificant.

These survival parameters were comparable also for CLL patients with mutated IGHV3-21 gene usage and expression the others mutated IGHV genes.

Furthermore, in small group of 6 patients with mutated IGHV3-21 gene expression, 3 patients had solid tumors and one underwent Richter transformation.

Unmutated IGHV3-21 gene expressed patients had worse OS and PFS in comparison with CLL patients that expressed the others unmutated IGHV genes.

[MeSH-major] Gene Expression. Genes, Immunoglobulin Heavy Chain. Leukemia, Lymphocytic, Chronic, B-Cell / genetics. Neoplasms, Second Primary / genetics

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(PMID = 18004251.001).

[ISSN] 1812-9269

[Journal-full-title] Experimental oncology

[ISO-abbreviation] Exp. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] Ukraine

[Chemical-registry-number] 0 / Immunoglobulin Variable Region

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Overexpression of the VAV proto-oncogene product is associated with B-cell chronic lymphocytic leukaemia displaying loss on 13q.

The expression of the VAV proto-oncogene in 57 patients with chronic myeloproliferative disease (CMD), B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin Lymphoma (B-NHL), and 61 with B-cell chronic lymphocytic leukaemia (B-CLL) was analysed.

Overexpression was not observed in B-ALL or CMD, but 13% of B-NHL and 34.4% of B-CLL patients (P = 0.002) overexpressed VAV.

The overexpression and phosphorylation of VAV was detected more frequently in 13q- chronic lymphocytic leukaemias (71.4%) versus other B-CLLs (23.4%, P = 0.001).

Overexpression of VAV protein is a frequent event in patients with B-CLL displaying loss of 13q sequences.

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[Cites] Mol Cell Biol. 2000 Mar;20(5):1461-77 [10669724.001]

[Cites] Mol Cell Biol. 2000 Mar;20(5):1678-91 [10669745.001]

[Cites] Haematologica. 2000 May;85(5):481-5 [10800163.001]

[Cites] EMBO J. 2005 Apr 6;24(7):1330-40 [15775967.001]

[Cites] EMBO J. 2003 Jul 1;22(13):3326-36 [12839994.001]

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[Cites] Nature. 2002 Dec 12;420(6916):629-35 [12478284.001]

(PMID = 16704440.001).

[ISSN] 0007-1048

[Journal-full-title] British journal of haematology

[ISO-abbreviation] Br. J. Haematol.

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / R01 CA073735; United States / NCI NIH HHS / CA / 5R01-CA73735-08

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Proto-Oncogene Proteins c-vav

[Other-IDs] NLM/ NIHMS22208; NLM/ PMC1950221

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [B-cell chronic lymphocytic leukaemia and the similar states].

[Transliterated title] Chronická B-lymfatická leukemie a jí podobné stavy.

B-cell chronic lymphocytic leukaemia and the similar diseases are seen predominantly in patients above the age 50 years, i.e. at the age when the patients also have other co-morbidities.

The aim of the present review is to provide the medical community with the main information on this disease as patients with B-cell chronic lymphocytic leukaemia and similar disease states are of older age and very often suffer from a range of co-morbidities.

The aim of the following text is to present a clear overview of the basic information about this group of diseases that might be useful to all physicians who provide care to patients with B-cell chronic lymphocytic leukaemia and similar conditions.

Since monoclonal immunoglobulin is sometimes identified in patients with these diseases, it is important to consider these conditions in the differential diagnosis of the states with the presence of monoclonal immunoglobulin.

[MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis

[MeSH-minor] Diagnosis, Differential. Humans. Leukemia, Hairy Cell / diagnosis. Leukemia, Prolymphocytic / diagnosis. Multiple Myeloma / diagnosis. Paraproteinemias / diagnosis

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(PMID = 19785372.001).

[ISSN] 0042-773X

[Journal-full-title] Vnitr̆ní lékar̆ství

[ISO-abbreviation] Vnitr Lek

[Language] cze

[Publication-type] English Abstract; Journal Article; Review

[Publication-country] Czech Republic

[Number-of-references] 41

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Community-based phase II trial of pentostatin, cyclophosphamide, and rituximab (PCR) biochemotherapy in chronic lymphocytic leukemia and small lymphocytic lymphoma.

We conducted a multicenter, community-based phase II trial of PCR biochemotherapy (pentostatin 4 mg/m2, cyclophosphamide 600 mg/m2, and rituximab 375 mg/m2) every 3 weeks for up to 6 cycles in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The median age of patients was 69 years; 11 patients were over age 70, and 71% had Rai stage III or IV disease.

No patients developed progressive disease while receiving PCR.

This is the first report of a trial in CLL utilizing a combination of purine analog, alkylator, and rituximab, in which most patients were older than 65 years and had high-risk disease.

PCR is active in CLL/SLL, but appears to be less active and associated with more complications in the community setting, compared to trials with younger, lower risk patients who travel to academic referral centers for treatment.

[MeSH-major] Antibodies, Monoclonal / immunology. Antibodies, Monoclonal / therapeutic use. Cyclophosphamide / therapeutic use. Delivery of Health Care. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Pentostatin / therapeutic use

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[CommentIn] Cancer Biother Radiopharm. 2007 Oct;22(5):713-4; author reply 715-7 [17979574.001]

(PMID = 17600465.001).

[ISSN] 1084-9785

[Journal-full-title] Cancer biotherapy & radiopharmaceuticals

[ISO-abbreviation] Cancer Biother. Radiopharm.

[Language] eng

[Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Membrane Glycoproteins; 143891-49-0 / TI 1 protein, Mustela vison; 395575MZO7 / Pentostatin; 4F4X42SYQ6 / Rituximab; 8N3DW7272P / Cyclophosphamide

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression.

They can transfer various messages to target cells and may be critical to disease progression.

Here, we demonstrate that MVs circulating in plasma of B-cell chronic lymphocytic leukemia (CLL) patients exhibit a phenotypic shift from predominantly platelet derived in early stage to leukemic B-cell derived at advanced stage.

Furthermore, the total MV level in CLL was significantly greater compared with healthy subjects.

To understand the functional implication, we examined whether MVs can interact and modulate CLL bone marrow stromal cells (BMSCs) known to provide a "homing and nurturing" environment for CLL B cells.

We found that CLL-MV can activate the AKT/mammalian target of rapamycin/p70S6K/hypoxia-inducible factor-1alpha axis in CLL-BMSCs with production of vascular endothelial growth factor, a survival factor for CLL B cells.

This study demonstrates the existence of separate MV phenotypes during leukemic disease progression and underscores the important role of MVs in activation of the tumor microenvironment.

[MeSH-major] Bone Marrow Cells / pathology. Cell-Derived Microparticles / pathology. Leukemia, Lymphocytic, Chronic, B-Cell / pathology

[MeSH-minor] Cell Line. Disease Progression. Glycogen Synthase Kinase 3 / metabolism. Humans. Hypoxia-Inducible Factor 1, alpha Subunit / metabolism. Intracellular Signaling Peptides and Proteins / metabolism. Microscopy, Electron, Transmission. Protein-Serine-Threonine Kinases / metabolism. Proto-Oncogene Proteins c-akt / metabolism. Ribosomal Protein S6 Kinases, 70-kDa / metabolism. Signal Transduction. Stromal Cells / metabolism. Stromal Cells / pathology. TOR Serine-Threonine Kinases. Tumor Cells, Cultured. Vascular Endothelial Growth Factor A / metabolism. beta Catenin / metabolism

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(PMID = 20018914.001).

[ISSN] 1528-0020

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

[Grant] United States / NCI NIH HHS / CA / R01 CA078383; United States / NCI NIH HHS / CA / R01 CA116237

[Publication-type] Journal Article; Research Support, N.I.H., Extramural

[Publication-country] United States

[Chemical-registry-number] 0 / CTNNB1 protein, human; 0 / HIF1A protein, human; 0 / Hypoxia-Inducible Factor 1, alpha Subunit; 0 / Intracellular Signaling Peptides and Proteins; 0 / VEGFA protein, human; 0 / Vascular Endothelial Growth Factor A; 0 / beta Catenin; EC 2.7.1.1 / MTOR protein, human; EC 2.7.1.1 / TOR Serine-Threonine Kinases; EC 2.7.11.1 / Protein-Serine-Threonine Kinases; EC 2.7.11.1 / Proto-Oncogene Proteins c-akt; EC 2.7.11.1 / Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1 / glycogen synthase kinase 3 beta; EC 2.7.11.26 / Glycogen Synthase Kinase 3

[Other-IDs] NLM/ PMC2832808

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Chromosomal abnormalities detected by multicolor fluorescence in situ hybridization in fine-needle aspirates from patients with small lymphocytic lymphoma are useful for predicting survival.

BACKGROUND: Fine-needle aspiration (FNA) of lymph nodes is commonly used to assess disease progression in patients with small lymphocytic lymphoma (SLL).

Although cytologic features are helpful for diagnosing typical SLL and transformed large-cell lymphoma (tLCL), SLL in accelerated phase (SLLacc) is more difficult to diagnose.

Additional tests are needed to identify those patients who are transforming to a higher-grade lymphoma.

This study evaluated the use of a multicolor fluorescence in situ hybridization (FISH) probe panel specifically designed for chronic lymphocytic leukemia (CLL)/SLL and assessed the association between FISH findings and cytologic diagnosis, proliferation index, and risk of death.

METHODS: FNA specimens from 50 patients (32 men and 18 women; mean age, 57 years [range, 36-77 years]) with histologically confirmed CLL and/or SLL were evaluated in this study for chromosomal abnormalities of 11q22 (ATM), 12, 13q14.3, 13q34.3 (LAMP1), and 17p13.1 (p53) by using a multiprobe FISH kit.

CONCLUSIONS: FISH can be performed on FNA specimens from patients with a history of SLL/CLL.

[MeSH-major] Biopsy, Fine-Needle. Chromosome Aberrations. In Situ Hybridization, Fluorescence. Leukemia, Lymphocytic, Chronic, B-Cell / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / mortality

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[Copyright] (c) 2008 American Cancer Society.

(PMID = 18683215.001).

[ISSN] 0008-543X

[Journal-full-title] Cancer

[ISO-abbreviation] Cancer

[Language] eng

[Grant] United States / NCI NIH HHS / CA / P30 CA016672

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] CMC-544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: analyses in cell lines and cells from patients with B-cell chronic lymphocytic leukaemia and lymphoma.

The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro.

The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR.

Cells obtained from 19 patients with B-cell CLL or NHL were also used.

The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution.

A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22.

In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp (P = 0.003), and to intracellular rhodamine-123 accumulation (P < 0.001).

Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.

[MeSH-major] Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Lymphoma, Non-Hodgkin / drug therapy

[MeSH-minor] Antibodies, Monoclonal, Humanized. Cell Count. Cell Line, Transformed. Cell Line, Tumor. Cyclosporins / therapeutic use. Dose-Response Relationship, Drug. Drug Resistance, Multiple / drug effects. Drug Resistance, Neoplasm. Flow Cytometry. Humans. Immunosuppressive Agents / therapeutic use. Jurkat Cells. P-Glycoprotein / analysis. P-Glycoprotein / antagonists & inhibitors. P-Glycoprotein / metabolism. Quinolines / therapeutic use. Sialic Acid Binding Ig-like Lectin 2 / analysis. Sialic Acid Binding Ig-like Lectin 2 / immunology. Treatment Outcome. Tumor Cells, Cultured

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(PMID = 19388933.001).

[ISSN] 1365-2141

[Journal-full-title] British journal of haematology

[ISO-abbreviation] Br. J. Haematol.

[Language] eng

[Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / Cyclosporins; 0 / Immunosuppressive Agents; 0 / Inotuzumab Ozogamicin; 0 / P-Glycoprotein; 0 / Quinolines; 0 / Sialic Acid Binding Ig-like Lectin 2; 0BJK6B565B / dofequidar; 121584-18-7 / valspodar

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] ZAP-70 and CD38 expression are independent prognostic factors in patients with B-cell chronic lymphocytic leukaemia and combined analysis improves their predictive value.

Recently identified biological risk factors in B-cell chronic lymphocytic leukemia (B-CLL) include ZAP-70 and CD38 expression.

We examined the expression of ZAP-70 and CD38 by flow cytometry method in 217 newly diagnosed, consecutive, unselected and well characterized B-CLL patients in relation to laboratory parameters and clinical outcome.

We confirmed that both ZAP-70 as well as CD38 were independent of prognostic factors.

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(PMID = 18519230.001).

[ISSN] 1897-5631

[Journal-full-title] Folia histochemica et cytobiologica

[ISO-abbreviation] Folia Histochem. Cytobiol.

[Language] ENG

[Publication-type] Journal Article

[Publication-country] Poland

[Chemical-registry-number] EC 2.7.10.2 / ZAP-70 Protein-Tyrosine Kinase; EC 2.7.10.2 / ZAP70 protein, human; EC 3.2.2.5 / Antigens, CD38

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The expression of NK cell inhibitory receptors on cytotoxic T cells in B-cell chronic lymphocytic leukaemia (B-CLL).

Reduced reactivity of CTL towards tumour cells could thus lead to disease progression and loss of tumour control.

In B-cell chronic lymphocytic leukaemia (B-CLL), the function of tumour-reactive CTL seems to correlate inversely to disease stage.

Inhibitory NK cell receptors are known to suppress the CTL response upon interaction with major histocompatibility complex (MHC) class I and increased expression of such receptors on CTL may inhibit the anti-tumour response.

So, the aim of this study was to investigate the expression of NK cell inhibitory receptors on CTL in B-CLL patients and if such expression correlated to disease stage.

CD8+ T cells from B-CLL patients in Binet stage A (n = 26) and stage C (n = 14) and healthy controls (n = 14) were analysed for the expression of killer immunoglobulin-like receptors (KIR) CD158a (KIR2DL1), CD158b (KIR2DL2), CD158e (KIR3DL1) and the C-type lectin receptor CD94, by flow cytometry analysis.

Patients with advanced disease (Binet stage C) had a significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than patients with non-progressive disease (Binet stage A) and healthy controls.

Our results suggest that increased expression of KIR and CD94 on CTL in advanced stage B-CLL may potentially contribute to the impaired anti-tumour immune response in these patients.

[MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / metabolism. Receptors, Immunologic / metabolism. T-Lymphocytes, Cytotoxic / metabolism

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(PMID = 17043777.001).

[ISSN] 1432-0584

[Journal-full-title] Annals of hematology

[ISO-abbreviation] Ann. Hematol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Germany

[Chemical-registry-number] 0 / Antigens, CD; 0 / KIR2DL2 protein, human; 0 / KIR3DL1 protein, human; 0 / Receptors, Immunologic; 0 / Receptors, KIR; 0 / Receptors, KIR2DL1; 0 / Receptors, KIR2DL2; 0 / Receptors, KIR2DL3; 0 / Receptors, KIR3DL1

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Expression of bone morphogenetic proteins (BMPs) receptors in patients with B-cell chronic lymphocytic leukemia (B-CLL).

They regulate proliferation, differentiation, and apoptosis in a variety of cells including hematopoietic cells.

BMPs act because of binding to two types of serine/threonine kinase receptors: BMP type I receptors (IA and IB) and BMP type II receptor.

The aim of our study was to examine the percentage of expression of BMPs receptors on lymphocytes of patients with B-cell chronic lymphocytic leukemia (B-CLL).

A total of 46 patients with B-CLL (27 men and 19 women) and 10 healthy persons were evaluated.

On cells of patients with B-CLL, the percentage of expression of BMP RIA, BMP RIB, and BMP RII was significantly higher than in normal cells of the control group.

The percentage of the expression of BMP RIA and BMP RIB was higher in patients with advanced stage of disease.

[MeSH-major] Bone Morphogenetic Protein Receptors, Type I / biosynthesis. Bone Morphogenetic Protein Receptors, Type II / biosynthesis. Leukemia, Lymphocytic, Chronic, B-Cell / physiopathology

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[Copyright] © 2010 Blackwell Publishing Ltd.

(PMID = 20491995.001).

[ISSN] 1751-553X

[Journal-full-title] International journal of laboratory hematology

[ISO-abbreviation] Int J Lab Hematol

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

[Chemical-registry-number] EC 2.7.11.30 / Bone Morphogenetic Protein Receptors; EC 2.7.11.30 / Bone Morphogenetic Protein Receptors, Type I; EC 2.7.11.30 / Bone Morphogenetic Protein Receptors, Type II

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Detection of t(14;18)(q32;q21) in B-cell chronic lymphocytic leukemia.

Cytomorphologic testing and multiparameter flow cytometry are the mainstays in diagnosing B-cell chronic lymphocytic leukemia, whereas fluorescence in situ hybridization that targets the translocation t(14;18)(q32;q21) often is used to identify follicular lymphoma.

We describe a case with cytomorphologically and immunologically proven B-cell chronic lymphocytic leukemia in which t(14;18)(q32;q21) was found.

[MeSH-major] Chromosomes, Human, Pair 14 / genetics. Chromosomes, Human, Pair 18 / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis. Translocation, Genetic / genetics

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(PMID = 15737042.001).

[ISSN] 1543-2165

[Journal-full-title] Archives of pathology & laboratory medicine

[ISO-abbreviation] Arch. Pathol. Lab. Med.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL).

Molecular markers like IgV(H) mutational status, chromosomal abnormalities, and CD38 and ZAP-70 expression have prognostic value in B-cell chronic lymphocytic leukemia (B-CLL).

These may be pathogenetic because of the coincidental expression of ZAP-70 and increased B-cell receptor (BCR) signaling and the signaling function of CD38 in CLL.

This study shows that ZAP-70(+) CLL B cells respond in vitro more readily than ZAP-70(-) CLL and normal B cells to chemokine migratory signals through enhanced surface CCR7 expression (P = .009; P < .001) and increased responsiveness to its ligands CCL19 and CCL21, demonstrated by F-actin polymerization (P < .05) and cellular migration (P < .01).

In addition, ZAP-70(+) CLL cells exhibit sustained ERK phosphorylation/activation following stimulation with CXCL12 (SDF1-alpha, a survival factor produced by stromal cells) compared with ZAP-70(-) cells (P = .004).

Following coculture with nurse-like cells, the survival of ZAP-70(+) but not ZAP-70(-) CLL cells is significantly enhanced by the addition of CXCL12 (P < .05), an effect that is partially blocked by the MEK inhibitor PD98059.

These advantageous migratory and survival responses may promote easier access to and greater proliferation in pseudo-germinal centers and explain in part the more progressive nature of ZAP-70(+) disease.

[MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / enzymology. Leukemia, Lymphocytic, Chronic, B-Cell / immunology. ZAP-70 Protein-Tyrosine Kinase / metabolism

[MeSH-minor] Case-Control Studies. Cell Movement. Cell Survival. Chemokine CCL19. Chemokine CCL21. Chemokine CXCL12. Chemokines, CC / pharmacology. Chemokines, CXC / pharmacology. Genes, Immunoglobulin. Humans. In Vitro Techniques. MAP Kinase Signaling System / drug effects. Models, Biological. Mutation. Receptors, CCR7. Receptors, CXCR4 / metabolism. Receptors, Chemokine / metabolism. Signal Transduction

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(PMID = 16332969.001).

[ISSN] 0006-4971

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / CCL19 protein, human; 0 / CCL21 protein, human; 0 / CCR7 protein, human; 0 / CXCL12 protein, human; 0 / Chemokine CCL19; 0 / Chemokine CCL21; 0 / Chemokine CXCL12; 0 / Chemokines, CC; 0 / Chemokines, CXC; 0 / Receptors, CCR7; 0 / Receptors, CXCR4; 0 / Receptors, Chemokine; EC 2.7.10.2 / ZAP-70 Protein-Tyrosine Kinase; EC 2.7.10.2 / ZAP70 protein, human

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Positive regulation of deoxycytidine kinase activity by phosphorylation of Ser-74 in B-cell chronic lymphocytic leukaemia lymphocytes.

Here, we show that dCK from B-cell chronic lymphocytic leukaemia (B-CLL) lymphocytes can be detected by an anti-phospho-Ser-74 antibody and that interindividual variability in dCK activity is related to its phosphorylation level on Ser-74.

[MeSH-major] Deoxycytidine Kinase / metabolism. Leukemia, Lymphocytic, Chronic, B-Cell / metabolism. Serine / metabolism

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(PMID = 17350163.001).

[ISSN] 0304-3835

[Journal-full-title] Cancer letters

[ISO-abbreviation] Cancer Lett.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Ireland

[Chemical-registry-number] 0 / Antibodies; 17885-08-4 / Phosphoserine; 452VLY9402 / Serine; EC 2.7.1.74 / Deoxycytidine Kinase

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL).

Deletions and/or mutations of p53 are relatively rare and late events in the natural history of B-cell chronic lymphocytic leukemia (B-CLL).

However, it is unknown whether p53 signaling is functional in B-CLL and if targeted nongenotoxic activation of the p53 pathway by using nutlin-3, a small molecule inhibitor of the p53/MDM2 interaction, is sufficient to kill B-CLL cells.

In vitro treatment with nutlin-3 induced a significant cytotoxicity on primary CD19(+) B-CLL cells, but not on normal CD19(+) B lymphocytes, peripheral-blood mononuclear cells, or bone marrow hematopoietic progenitors.

Among 29 B-CLL samples examined, only one was resistant to nutlin-3-mediated cytotoxicity.

The induction of p53 by nutlin-3 in B-CLL samples was accompanied by alterations of the mitochondrial potential and activation of the caspase-dependent apoptotic pathway.

Moreover, nutlin-3 synergized with both fludarabine and chlorambucil in inducing B-CLL apoptosis.

Our data strongly suggest that nutlin-3 should be further investigated for clinical applications in the treatment of B-CLL.

[MeSH-major] Imidazoles / pharmacology. Leukemia, Lymphocytic, Chronic, B-Cell / blood. Piperazines / pharmacology. Tumor Suppressor Protein p53 / blood

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(PMID = 16439677.001).

[ISSN] 0006-4971

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Imidazoles; 0 / Piperazines; 0 / Tumor Suppressor Protein p53; 0 / nutlin 3

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [T-PA and PAI-1 in lymphocytes of patients with chronic lymphoid leukemia].

[Transliterated title] T-PA i PAI-1 w limfocytach u chorych na przewlekła białaczke limfatyczna.

The aim was the evaluation of t-PA (tissue plasminogen activator) and PAI-1 (inhibitor of plasminogen activator type 1) in lymphocytes datained from patients with chronic lymphoid leukemia.

INVESTIGATED GROUP: The study was performed in 35 patients with chronic lymphoid leukemia and in control group containing 20 healthy persons.

From venous blood lymphocytes were isolated, calculated and homogenized using ultrasound disintegrator.

RESULTS: In lymphocytes obtained from healthy persons more t-PA and PAI-1 was detected than in lymphocytes from patients with chronic lymphoid leukemia.

In lymphocytes from patients PAI-1: Ag concentration was 14 fold higher than t-PA:Ag.

CONCLUSION: The lymphocytes of patients suffering from chronic lymphoid leukemia are different from healthy person in respect of t-PA:Ag and PAI-1:Ag concentration.

[MeSH-major] Leukemia, Lymphoid / blood. Lymphocytes / blood. Plasminogen Activator Inhibitor 1 / blood. Tissue Plasminogen Activator / blood

[MeSH-minor] Adult. Aged. Aged, 80 and over. Case-Control Studies. Chronic Disease. Female. Humans. Male. Middle Aged

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(PMID = 18468424.001).

[Journal-full-title] Polskie Archiwum Medycyny Wewnetrznej

[ISO-abbreviation] Pol. Arch. Med. Wewn.

[Language] pol

[Publication-type] English Abstract; Journal Article

[Publication-country] Poland

[Chemical-registry-number] 0 / Plasminogen Activator Inhibitor 1; 0 / SERPINE1 protein, human; EC 3.4.21.68 / Tissue Plasminogen Activator