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[Title] MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation.

Increasing evidence shows aberrant hypermethylation of genes occurring in and potentially contributing to pathogenesis of myeloid malignancies.

To determine the extent of promoter hypermethylation in such tumors, we compared the distribution of DNA methylation of 14 000 promoters in MDS and secondary acute myeloid leukemia (AML) patients enrolled in a phase 1 trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34(+) bone marrow cells.

The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34(+) bone marrow cells or de novo AML blasts.

Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu-poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways.

[MeSH-major] Azacitidine / administration & dosage. DNA Methylation / drug effects. DNA, Neoplasm / metabolism. Enzyme Inhibitors / administration & dosage. Leukemia, Myeloid, Acute. Myelodysplastic Syndromes. Neoplasms, Second Primary / drug therapy. Neoplasms, Second Primary / metabolism

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[CommentIn] Blood. 2009 Oct 15;114(16):3363-4 [19833849.001]

(PMID = 19652201.001).

[ISSN] 1528-0020

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

[Databank-accession-numbers] ClinicalTrials.gov/ NCT00101179

[Grant] United States / NCI NIH HHS / CA / R21 CA110507; United States / NCI NIH HHS / CA / U10 CA021115; United States / NCI NIH HHS / CA / U54 CA143876-01; United States / NCI NIH HHS / CA / K24 CA111717; United States / NCI NIH HHS / CA / R01 CA125635; United States / NCI NIH HHS / CA / U01 CA070095; United States / NCI NIH HHS / CA / U54 CA143876; United States / NICHD NIH HHS / HD / R01 HD044078; United States / NCI NIH HHS / CA / CA21115; United States / NCI NIH HHS / CA / U24 CA114737; United States / NCI NIH HHS / CA / R01 CA104348; United States / NCI NIH HHS / CA / U01CA70095

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

[Publication-country] United States

[Chemical-registry-number] 0 / Antigens, CD34; 0 / DNA, Neoplasm; 0 / Enzyme Inhibitors; 0 / Histone Deacetylase Inhibitors; 0 / Wnt Proteins; EC 3.5.1.98 / Histone Deacetylases; M801H13NRU / Azacitidine

[Other-IDs] NLM/ PMC2765680

   

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

[Title] Long-term remissions in patients with myelodysplastic syndrome and secondary acute myelogenous leukemia undergoing allogeneic transplantation following a reduced intensity conditioning regimen of 550 cGy total body irradiation and cyclophosphamide.

We analyzed outcomes of patients with myelodysplastic syndrome (MDS) or secondary acute myelogenous leukemia (sAML) that were treated at our institution with a reduced intensity conditioning (RIC) regimen of 550-cGy total body irradiation and cyclophosphamide followed by related donor (RD) or unrelated donor (URD) transplantation.

[MeSH-major] Bone Marrow Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Neoplasms, Second Primary / therapy. Peripheral Blood Stem Cell Transplantation / methods. Transplantation Conditioning / methods

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(PMID = 16785064.001).

[ISSN] 1083-8791

[Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

[ISO-abbreviation] Biol. Blood Marrow Transplant.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Myeloablative Agonists; 8N3DW7272P / Cyclophosphamide

   

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

[Title] Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia.

BACKGROUND: Response and survival in 96 patients with secondary acute myeloid leukemia (sAML) who received aggressive induction chemotherapy was reviewed.

Patients with AML after previous chemotherapy or radiation therapy had a higher morphologic remission rate compared with those arising from myelodysplastic syndrome or myeloproliferative disease (82% vs 62%; P = .027).

In this population of patients who received aggressive chemotherapy, Charlson comorbidity index or a higher number of factors recognized as high risk in leukemia patients did not affect the chance of OS, DFS, and EFS, although having more recognized leukemia risk factors was related to a lower chance of surviving 1 year.

[MeSH-major] Leukemia, Myeloid, Acute / drug therapy. Neoplasms, Second Primary / drug therapy

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(PMID = 19452542.001).

[ISSN] 0008-543X

[Journal-full-title] Cancer

[ISO-abbreviation] Cancer

[Language] eng

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

[Publication-country] United States

   

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

[Title] [Survival in adults with acute myelogenous leukemia].

BACKGROUND: Acute myelogenous leukemia is the most common type of acute leukemia in adults.

MATERIAL AND METHODS: Survival data were retrieved from the Norwegian Registry for Acute Leukemias and Lymphoblastic Lymphomas for patients with acute myelogenous leukemia (aged from 16 to 60 years) who were registered in the period 1.1.2000-31.12.2005.

Patients with secondary acute myelogenous leukemia were classified as high-risk.

RESULTS AND INTERPRETATION: 4-year survival was 94.5% in acute promyelocytic leukemia, 77.7% in other low-risk acute myelogenous leukemia, 39.0% in standard risk patients and 29.1% in high-risk patients.

The increase is most probably due to an intensification of chemotherapy after remission and to the implementation of all-trans-retinoic acid in the treatment of promyelocytic leukemia.

[MeSH-major] Leukemia, Myeloid, Acute / mortality

[MeSH-minor] Adolescent. Adult. Age Factors. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Female. Humans. Leukemia, Promyelocytic, Acute / drug therapy. Leukemia, Promyelocytic, Acute / genetics. Leukemia, Promyelocytic, Acute / mortality. Male. Middle Aged. Neoplasm Recurrence, Local / mortality. Norway / epidemiology. Risk Factors. Survival Rate

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[CommentIn] Tidsskr Nor Laegeforen. 2008 Aug 14;128(15):1681-2; author reply 1682 [18704137.001]

(PMID = 18480864.001).

[ISSN] 0807-7096

[Journal-full-title] Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række

[ISO-abbreviation] Tidsskr. Nor. Laegeforen.

[Language] nor

[Publication-type] Comparative Study; English Abstract; Journal Article

[Publication-country] Norway

   

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

[Title] Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor?

PURPOSE: To describe a series of patients with secondary acute myelogenous leukemia (sAML) and retinoblastoma (RB).

MAIN OUTCOME MEASURES: History of RB and development of sAML, management of RB (surgery, radiotherapy, chemotherapy), age at diagnosis of RB and leukemia, French-American-British (FAB) subtype, and current status of patient (alive or dead).

Mean latent period from RB to AML diagnosis was 9.8 years (median, 42 months).

Ten children died of their leukemia.

CONCLUSIONS: Acute myelogenous leukemia is a rare secondary malignancy among retinoblastoma patients, many of whom were treated with primary or adjuvant chemotherapy.

[MeSH-major] Antineoplastic Agents, Phytogenic / adverse effects. Enzyme Inhibitors / adverse effects. Leukemia, Myeloid, Acute / chemically induced. Neoplasms, Second Primary / chemically induced. Podophyllotoxin / adverse effects. Retinal Neoplasms / drug therapy. Retinoblastoma / drug therapy. Topoisomerase II Inhibitors

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(PMID = 17613328.001).

[ISSN] 1549-4713

[Journal-full-title] Ophthalmology

[ISO-abbreviation] Ophthalmology

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 0 / Enzyme Inhibitors; 0 / Topoisomerase II Inhibitors; L36H50F353 / Podophyllotoxin

[Number-of-references] 42

   

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

[Title] Acute myelogenous leukemia in older adults.

The incidence of acute myelogenous leukemia (AML) increases with age.

Older AML patients, generally defined by age > or = 60 years, have worse treatment outcomes than younger patients.

Older patients are more likely to present with unfavorable cytogenetic abnormalities, multidrug resistance phenotypes, and secondary AML.

Investigations of hypomethylating agents and signal transduction inhibitors hold promise for the treatment of AML patients.

[MeSH-major] Geriatrics / methods. Leukemia, Myeloid, Acute / pathology. Leukemia, Myeloid, Acute / therapy

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(PMID = 19282349.001).

[ISSN] 1549-490X

[Journal-full-title] The oncologist

[ISO-abbreviation] Oncologist

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Number-of-references] 72

   

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

[Title] Acute promyelocytic leukemia relapsing as secondary acute myelogenous leukemia with translocation t(3;21)(q26;q22) and RUNX1-MDS1-EVI1 fusion transcript.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by peculiar clinical and biologic features, including severe hemorrhagic diathesis, specific recurrent chromosomal aberration, and distinct morphologic features with predominant pathologic promyelocytes.

A reciprocal translocation involving chromosomes 15 and 17, t(15;17)(q22;q21), is a characteristic feature of APL that represents approximately 5-8% of AML.

In contrast to other AML subtypes, APL is particularly sensitive to treatment with all trans-retinoic acid (ATRA) combined with chemotherapy, converting this once fatal leukemia to a highly curable disease.

Nonetheless, therapy-related myelodysplastic syndrome-acute myelogenous leukemia (t-MDS/AML) has been reported as a rare complication of chemotherapy in APL.

Of 30 APL cases described as t-MDS/AML in the literature, only 1 case relapsed as acute leukemia with t(3;21)(q26;q22).

Here we describe a rare case of APL relapsing as secondary AML with t(3;21)(q26;q22) and clinically characterize this patient using the RUNX1 (previously AML1)-MDS1-EVI1 fusion transcript (with follow-up for 55 months), and review the relevant literature.

[MeSH-major] Leukemia, Myeloid, Acute / genetics. Leukemia, Promyelocytic, Acute / genetics. Neoplasms, Second Primary / genetics. Oncogene Proteins, Fusion / genetics. Translocation, Genetic

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(PMID = 19027486.001).

[ISSN] 1873-4456

[Journal-full-title] Cancer genetics and cytogenetics

[ISO-abbreviation] Cancer Genet. Cytogenet.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Core Binding Factor Alpha 2 Subunit; 0 / DNA-Binding Proteins; 0 / MECOM protein, human; 0 / Neoplasm Proteins; 0 / Oncogene Proteins, Fusion; 0 / RUNX1 protein, human; 0 / Transcription Factors; 0 / promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; 5688UTC01R / Tretinoin

   

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

[Title] Long-term follow-up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia.

We report on the outcomes of 53 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS, autografted in first complete remission.

[MeSH-major] Leukemia, Myeloid, Acute / surgery. Myelodysplastic Syndromes / surgery. Stem Cell Transplantation

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(PMID = 16531261.001).

[ISSN] 1592-8721

[Journal-full-title] Haematologica

[ISO-abbreviation] Haematologica

[Language] eng

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

[Publication-country] Italy

[Chemical-registry-number] 0 / Antineoplastic Agents

   

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

[Title] Reasons for treating secondary AML as de novo AML.

In a Danish bi-regional registry-based study, we conducted an analysis of the incidence and clinical importance of secondary acute myeloid leukaemia (AML).

In a total of 630 cases of AML, we found 157 (25%) cases of secondary AML.

The secondary leukaemia arose from MDS (myelodysplastic syndrome) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy-related AML (t-AML) in 37 cases (24%).

Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006).

In univariate analyses, secondary AML was associated with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease-free survival (DFS) of secondary cases was equal to that of de novo cases.

Interestingly, in all further analyses of CR-rates, OS and DFS, when correcting for the influence of age, cytogenetic abnormalities, performance status and leucocyte count (WBC), presence of secondary AML completely lost prognostic significance.

We conclude that the presence of secondary AML does not per se convey an unfavourable prognosis and that patients with secondary AML should be offered the chance of benefiting from treatment according to current frontline AML protocols.

[MeSH-major] Leukemia, Myeloid, Acute / complications. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / complications

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(PMID = 20456491.001).

[ISSN] 1600-0609

[Journal-full-title] European journal of haematology

[ISO-abbreviation] Eur. J. Haematol.

[Language] eng

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

[Publication-country] England

   

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

[Title] Two cases of secondary acute myeloid leukemia accompanying adult T-cell leukemia/lymphoma.

We identified 2 cases of secondary acute myeloid leukemia (AML) following adult T-cell leukemia/lymphoma (ATL) in patients who had previously received chemotherapy.

Both cases were thought to represent therapy-related AML because the patients had previously received combination chemotherapy including epipodophyllotoxin, anthracycline, and alkylating agents for the ATL.

The cases were diagnosed as AML M4 with eosinophilia and AML M2, with the chromosomal abnormalities inv(16)(p13q22) and t(8;21)(q22;q22), respectively.

In our hospital, only these 2 cases of secondary AML accompanying ATL were identified among 90 cases of acute- or lymphoma-type ATL diagnosed from October 1999 to July 2006.

The frequency of coexisting AML and ATL is lower than that reported for acute leukemia coexisting with other lymphoid malignancies.

The low frequency of secondary leukemia with ATL may be associated with the short survival times of ATL patients.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Leukemia, Myeloid / chemically induced. Leukemia-Lymphoma, Adult T-Cell / complications. Neoplasms, Second Primary / chemically induced

[MeSH-minor] Acute Disease. Alkylating Agents / therapeutic use. Anthracyclines / therapeutic use. Chromosome Aberrations. Female. Humans. Leukemia, Myeloid, Acute / chemically induced. Leukemia, Myelomonocytic, Acute / chemically induced. Male. Middle Aged. Podophyllotoxin / therapeutic use

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(PMID = 17261499.001).

[ISSN] 0925-5710

[Journal-full-title] International journal of hematology

[ISO-abbreviation] Int. J. Hematol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Japan

[Chemical-registry-number] 0 / Alkylating Agents; 0 / Anthracyclines; L36H50F353 / Podophyllotoxin

   

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

[Title] Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).

We have identified a novel fusion partner of MLL, namely the mastermind like 2 (MAML2 gene), in secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with inv(11)(q21q23).

RT-PCR and sequencing revealed that exon 7 of MLL was fused to exon 2 of MAML2 in the AML and MDS cells.

MLL-MAML2 in secondary AML/MDS and MECT1-MAML2 in mucoepithelioid carcinoma, benign Wartin's tumor, and clear cell hidradenoma consist of the same COOH-terminal part of MAML2.

[MeSH-major] Chromosomes, Human, Pair 11 / genetics. DNA-Binding Proteins / genetics. Leukemia, Myeloid, Acute / genetics. Myelodysplastic Syndromes / genetics. Myeloid-Lymphoid Leukemia Protein / genetics. Nuclear Proteins / genetics. Oncogene Proteins, Fusion / genetics. Transcription Factors / genetics

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[Copyright] (c) 2007 Wiley-Liss, Inc.

(PMID = 17551948.001).

[ISSN] 1045-2257

[Journal-full-title] Genes, chromosomes & cancer

[ISO-abbreviation] Genes Chromosomes Cancer

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents; 0 / DNA-Binding Proteins; 0 / MAML2 protein, human; 0 / MLL protein, human; 0 / Nuclear Proteins; 0 / Oncogene Proteins, Fusion; 0 / Transcription Factors; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase

   

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

[Title] Prognosis of secondary acute myeloid leukemia is affected by the type of the preceding hematologic disorders and the presence of trisomy 8.

BACKGROUND: Differences in the clinical course of secondary acute myeloid leukemia according to the type of the preceding disorders are not defined.

We compared the outcomes of therapy-related acute myeloid leukemia, acute myeloid leukemia following myelodysplastic syndrome and acute myeloiod leukemia following myeloproliferative neoplasm.

We also intended to find prognostic factors in secondary acute myeloid leukemia overall.

RESULTS: Ninety-five secondary acute myeloid leukemia patients (median age of 56.4 years) were analyzed.

Twenty-six, 57 and 12 patients had therapy-related leukemia, leukemia following myelodysplastic syndrome and myeloproliferative neoplasm, respectively.

Compared to therapy-related leukemia (P = 0.027) and leukemia following myelodysplastic syndrome (P = 0.050), leukemia following myeloproliferative neoplasm had shorter overall survival.

In secondary leukemia, presence of trisomy 8 had a prognostic impact (P = 0.003) along with cytogenetic risk group (P = 0.016).

CONCLUSIONS: Prognosis of secondary acute myeloid leukemia was different according to the type of the preceding disorders with the worst prognosis in leukemia following myeloprolfierative neoplasm.

Along with cytogenetic risk grouping, trisomy 8 had a poor prognostic impact in secondary acute myeloid leukemia.

[MeSH-major] Chromosomes, Human, Pair 8 / genetics. Leukemia, Myeloid, Acute / etiology. Leukemia, Myeloid, Acute / genetics. Myelodysplastic Syndromes / complications. Myeloproliferative Disorders / complications. Trisomy

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(PMID = 20587614.001).

[ISSN] 1465-3621

[Journal-full-title] Japanese journal of clinical oncology

[ISO-abbreviation] Jpn. J. Clin. Oncol.

[Language] eng

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

[Publication-country] England

[Chemical-registry-number] 04079A1RDZ / Cytarabine; ZRP63D75JW / Idarubicin; ZS7284E0ZP / Daunorubicin

   

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

[Title] Low toxicity and efficacy of (153)samarium-EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia.

We report the case of a 15-yr-old girl who developed secondary acute myelogenous leukemia (AML) 4 yr after completion of therapy for metastatic Ewing sarcoma (primary right acetabulum with metastatic disease to the lungs).

[MeSH-major] Leukemia, Myeloid, Acute / therapy. Melphalan. Organometallic Compounds / therapeutic use. Organophosphorus Compounds / therapeutic use. Radioisotopes. Samarium. Transplantation Conditioning / methods

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(PMID = 15667625.001).

[ISSN] 1397-3142

[Journal-full-title] Pediatric transplantation

[ISO-abbreviation] Pediatr Transplant

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Denmark

[Chemical-registry-number] 0 / Organometallic Compounds; 0 / Organophosphorus Compounds; 0 / Radioisotopes; 122575-21-7 / samarium ethylenediaminetetramethylenephosphonate; 42OD65L39F / Samarium; Q41OR9510P / Melphalan

   

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

[Title] Incidence of therapy-related leukemia following chemoradiotherapy for esophageal cancer.

However, the frequency and the pathogenesis of secondary malignancies that is the most serious late-onset complication are still unclear.

RESULTS: Four patients, who achieved CR after CRT, developed leukemia.

Case1, 60-yo-male, developed overt acute myeloid leukemia (AML) from myelodysplastic syndrome 48 months after CRT.

Case2, 64-yo-male, developed AML M0 with t(9;22)(q34;q11) 44 months after CRT.

Case3, 72-yo-male, developed Burkitt leukemia with t(8;14)(q24;q32) 19 months after CRT.

Case4, 65-yo-male, developed myeloid crisis of chronic myelogenous leukemia with complicated abnormalities including t(9;22)(q34;q11) 48 months after CRT.

All patients eventually died of leukemia.

CONCLUSIONS: Since platinum and fluorouracil have shown relatively low chance of secondary neoplasm, our data demonstrates that the concurrent radiotherapy which involves massive bone marrow tissue may increase the risk of leukomogenesis.

To this end, atypical cytogenetic abnormalities seen in the present cases give a new insight into the biology of therapy-related leukemia.

Notably, this is the first report presenting the incidence of secondary leukemia by nedaplatin.

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(PMID = 27962759.001).

[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] Outcomes following induction chemotherapy in patients with AML arising from MDS: Analysis of prognostic factors.

: 7088 Background: Secondary acute myeloid leukemia (sAML) arising from myelodysplasia (MDS) or a myeloproliferative neoplasm (MPN) has a poor prognosis.

METHODS: Retrospective chart review of patients with untreated AML from MDS/MPN treated with standard induction therapy from January 2004 to September 2008.

Multivariable analysis indicated that the same three factors were significantly negatively associated with CR/CRp as well as OS: PR cytogenetics, prior treatment with DM/L, and long transformation to AML on log scale.

Only 32% of the group that received prior treatment with a DM/L achieved CR/CRp compared to 78% in non DM/L-treated patients (OR = 0.13, 95% CI: 0.04-0.42).

The median OS for those treated with a DM/L was 3.7 mo compared to 10.5 mo for non DM/L-treated patients (p < 0.0001).

CONCLUSIONS: Prior MDS treatment with a DM/L, PR cytogenetics and long transformation to AML are independent negative prognostic factors for response and OS in patients with sAML following induction therapy, suggesting that such patients may be better served by novel approaches, and that stratification for these risk factors should be considered in future clinical trials.

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(PMID = 27961482.001).

[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 pemetrexed in patients with relapsed or refractory acute leukemia or lymphoid blast phase chronic myelogenous leukemia.

The purpose of this phase I trial was to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of pemetrexed given with vitamin supplementation to patients with relapsed or refractory leukemia.

Secondary objectives were pharmacokinetic (PK) and pharmacodynamic (PD) analyses of pemetrexed.

METHODS: Patients ≥15 years of age were enrolled with relapsed or refractory leukemia, Eastern Cooperative Oncology Group performance status ≤2, adequate renal and hepatic function, and life expectancy of ≥6 weeks.

RESULTS: Twenty-two patients entered the trial; median age was 50 years (range: 18-75); 15 patients had acute myeloid leukemia and 7 patients had acute lymphocytic leukemia (ALL).

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(PMID = 27961463.001).

[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 study of voreloxin as single agent therapy for elderly patients (pts) with newly diagnosed acute myeloid leukemia (AML).

Interim results of REVEAL-1, a phase II study of single agent voreloxin in newly diagnosed elderly AML pts, are reported.

Eligibility: newly diagnosed AML (de novo or secondary AML), pts age ≥ 60 and ≥ 1 additional adverse risk factor (age ≥ 70, secondary AML, intermediate or unfavorable cytogenetics, or PS 2).

Voreloxin PK were similar to those in an earlier single agent phase I study in relapsed/refractory AML.

CONCLUSIONS: In REVEAL-1, voreloxin demonstrates clinical activity with 2 dosing schedules in previously untreated elderly (age ≥ 60) patients with AML who are unlikely to benefit from standard chemotherapy.

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(PMID = 27961427.001).

[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.

: 2053 Background: Secondary acute myeloid leukemia (AML) is reported to occur in 3%-10% of patients treated with alkylating agents for Hodgkin's lymphoma, non-Hodgkin's lymphoma, ovarian cancer, breast cancer, and multiple myeloma.

The incidence of secondary AML is greatest at 5-10 years after treatment, and AML often follows myelodysplastic syndrome (MDS).

Among these patients, we identified 140 cases that we labeled as major hematologic adverse events: agranulocytosis (8 cases), aplasia (42), aplastic anemia (52), leukemia (26), MDS (6), and lymphoma (6).

Risk of leukemia/MDS from our review may also be significant, but length of follow-up is insufficient and the real risk is likely still unknown.

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(PMID = 27964671.001).

[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] [High risk of cardiac dysfunction after treatment of secondary acute myeloid leukemia following chemotherapy and radiotherapy for breast cancer].

Secondary acute myeloid leukaemia (AML) occurring after breast cancer is a rare long-term complication of the chemo- and/or radiation therapy required to treat breast cancer.

The usually recognized curative option of these secondary AML includes courses of anthracycline-based chemotherapy followed by haematopoietic stem cell transplantation (HSCT).

Cardiac dysfunction during AML treatment of these patients previously treated with anthracyclines for breast cancer has not been reported to date.

We evaluated the evolution of cardiac function in seven patients treated with anthracyclines and/or autologous or allogeneic bone marrow transplantation for secondary AML occurring after breast cancer.

All of the patients who received a cumulative anthracycline dose above the cardiac toxicity threshold developed cardiac symptoms during AML chemotherapy courses.

Thus, the risk of severe cardiac dysfunction after treatment of secondary AML following breast cancer must be taken in account as part of the therapeutic strategy of those patients.

As discussed here, an accurate evaluation of risk factors, the use of sensitive detection tests and of cardioprotective drugs as well as that of non-cardiotoxic chemotherapy might decrease the occurrence and severity of this life-threatening complication.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Breast Neoplasms. Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myeloid / therapy. Neoplasms, Second Primary / therapy

[MeSH-minor] Acute Disease. Adult. Chemotherapy, Adjuvant / adverse effects. Cyclophosphamide / administration & dosage. Cyclophosphamide / adverse effects. Daunorubicin / administration & dosage. Daunorubicin / adverse effects. Epirubicin / administration & dosage. Epirubicin / adverse effects. Female. Fluorouracil / administration & dosage. Fluorouracil / adverse effects. Heart Diseases / chemically induced. Heart Diseases / drug therapy. Heart Diseases / physiopathology. Humans. Middle Aged. Remission Induction. Stroke Volume / drug effects. Stroke Volume / physiology

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(PMID = 19819776.001).

[ISSN] 1769-6917

[Journal-full-title] Bulletin du cancer

[ISO-abbreviation] Bull Cancer

[Language] fre

[Publication-type] English Abstract; Journal Article

[Publication-country] France

[Chemical-registry-number] 3Z8479ZZ5X / Epirubicin; 8N3DW7272P / Cyclophosphamide; U3P01618RT / Fluorouracil; ZS7284E0ZP / Daunorubicin; FEC protocol

   

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

[Title] Selective blast cell reduction in elderly patients with acute myeloid leukemia secondary to myelodysplastic syndrome treated with methylprednisolone.

The management of elderly patients with acute myeloid leukemia (AML) and a poor performance status is challenging.

An 89-year-old man with AML secondary to myelodysplastic syndrome (MDS) and a poor performance status (4) underwent treatment with methylprednisolone (mPSL) (125 mg/body), which resulted in a remarkable reduction of blast cells in the peripheral blood.

On the basis of this experience, we gave the same mPSL dose to other elderly patients with MDS/AML (n=5) or AML-M4 (n=1) who had a poor performance status (3 or higher) and appeared unable to tolerate standard cytotoxic chemotherapies.

Selective and significant blast cell reduction was observed in 4 of the 5 patients with MDS/AML, whereas no effects were seen in the AML patient.

Although our experience is limited, these findings may provide a clue to understanding the mechanisms regulating the survival of blast cells of MDS/AML and indicate that mPSL may provide a benefit to a subset of these patients.

[MeSH-major] Blast Crisis / drug therapy. Blast Crisis / etiology. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / etiology. Methylprednisolone / administration & dosage. Myelodysplastic Syndromes / complications. Myelodysplastic Syndromes / drug therapy

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[Cites] Leuk Res. 1999 Jul;23(7):603-13 [10400181.001]

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(PMID = 17483080.001).

[ISSN] 0925-5710

[Journal-full-title] International journal of hematology

[ISO-abbreviation] Int. J. Hematol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Japan

[Chemical-registry-number] X4W7ZR7023 / Methylprednisolone

   

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

[Title] XPD DNA nucleotide excision repair gene polymorphisms associated with DNA repair deficiency predict better treatment outcomes in secondary acute myeloid leukemia.

We evaluated these polymorphisms and XPD haplotypes in adult de novo (n=214) and secondary (n=79) acute myeloid leukemia (AML) patients treated with cytarabine and anthracycline chemotherapy.

Differential responses were observed in secondary, but not de novo, AML.

Among secondary AML patients, the odds of achieving complete remission (CR) were higher for the XPD 312Asn/Asn (OR= 11.23; 95% CI, 2.23-56.63) and XPD 751Gln/Gln (OR= 7.07; 95% CI, 1.42-35.18) genotypes.

If validated, these findings could support stratification of chemotherapy in secondary AML.

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(PMID = 21394217.001).

[ISSN] 1948-1756

[Journal-full-title] International journal of molecular epidemiology and genetics

[ISO-abbreviation] Int J Mol Epidemiol Genet

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / CA108353-02; United States / NCI NIH HHS / CA / R03 CA108353; United States / NCI NIH HHS / CA / CA108353-01; United States / NCI NIH HHS / CA / R03 CA108353-02; United States / NCI NIH HHS / CA / R03 CA108353-01

[Publication-type] Journal Article

[Publication-country] United States

[Other-IDs] NLM/ NIHMS247623; NLM/ PMC3049908

[Keywords] NOTNLM ; Acute Myeloid Leukemia (AML) / DNA repair gene polymorphisms / pharmacogenetics/pharmacogenomics / secondary AML

   

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

[Title] Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo core-binding factor leukemia.

BACKGROUND: Therapy related secondary acute myelogenous leukemia (AML) was commonly associated with prior exposure to alkylating agents or topoisomerase inhibitor.

The long-term outcome of such patients with secondary AML was found to be worse than that of patients with de novo AML.

Earlier reports suggested similar outcomes for patients with de novo and secondary AML associated with core-binding factor (CBF) abnormalities.

METHODS: A total of 188 patients with CBF AML were analyzed.

The frequency of secondary CBF AML was 9%.

RESULTS: Patients with secondary CBF AML were found to have significantly worse overall (OS) and event-free survival (EFS) compared with patients with de novo CBF AML.

Secondary CBF AML status appeared to have only marginal significance in multivariate analysis.

CONCLUSIONS: Matched analysis (by age, Eastern Cooperative Oncology Group performance status, and additional cytogenetic abnormality) indicated worse OS and EFS in patients with secondary CBF AML.

[MeSH-major] Core Binding Factors / metabolism. Leukemia, Myeloid, Acute / mortality. Neoplasms, Second Primary / mortality

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(PMID = 19441109.001).

[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

[Chemical-registry-number] 0 / Core Binding Factors; 04079A1RDZ / Cytarabine

[Other-IDs] NLM/ NIHMS629439; NLM/ PMC4184418

   

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

[Title] Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS).

We investigated a dose-reduced conditioning regimen consisting of treosulfan and fludarabine followed by allogeneic stem cell transplantation (SCT) in 26 patients with secondary AML or MDS.

Acute graft-versus-host disease (GvHD) grade II-IV was seen in 23% and severe grade III GvHD in 12% of the patients.

No patients experienced grade IV acute GvHD.

[MeSH-major] Antilymphocyte Serum / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Busulfan / analogs & derivatives. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid / therapy. Myelodysplastic Syndromes / therapy. Transplantation Conditioning / methods. Vidarabine / analogs & derivatives

[MeSH-minor] Acute Disease. Adult. Aged. Disease-Free Survival. Female. Graft vs Host Disease / drug therapy. Graft vs Host Disease / prevention & control. HLA Antigens / analysis. Humans. Male. Middle Aged. Prospective Studies. Recurrence. Siblings. Survival Rate. Transplantation, Homologous. Treatment Outcome

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(PMID = 16415898.001).

[ISSN] 0268-3369

[Journal-full-title] Bone marrow transplantation

[ISO-abbreviation] Bone Marrow Transplant.

[Language] eng

[Publication-type] Clinical Trial; Comparative Study; Journal Article

[Publication-country] England

[Chemical-registry-number] 0 / Antilymphocyte Serum; 0 / HLA Antigens; CO61ER3EPI / treosulfan; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine

   

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

[Title] The nonsteroidal anti-inflammatory drug Exisulind selectively induces apoptosis via JNK in secondary acute myeloid leukemia after myelodysplastic syndrome.

Treatment of patients suffering from myelodysplastic syndromes and secondary acute myeloid leukemia after MDS is often unsuccessful.

Exisulind is another potentially pro-apoptotic agent, and therefore, we investigated its influence on proliferation, differentiation, cell cycle and apoptosis in two sAML/MDS cell lines, one de-novo AML cell line and healthy CD34+ bone marrow cells.

Exisulind had no effect on de-novo AML or normal CD34+ cells.

[MeSH-major] Anti-Inflammatory Agents, Non-Steroidal / therapeutic use. Apoptosis / drug effects. JNK Mitogen-Activated Protein Kinases / metabolism. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / etiology. Myelodysplastic Syndromes / complications. Sulindac / analogs & derivatives

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(PMID = 15970671.001).

[ISSN] 1551-4005

[Journal-full-title] Cell cycle (Georgetown, Tex.)

[ISO-abbreviation] Cell Cycle

[Language] eng

[Grant] United States / NCI NIH HHS / CA / CA 85467

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

[Publication-country] United States

[Chemical-registry-number] 0 / Anti-Inflammatory Agents, Non-Steroidal; 0 / Antigens, CD34; 0 / GADD45 protein; 0 / Intracellular Signaling Peptides and Proteins; 184SNS8VUH / Sulindac; EC 2.7.11.24 / JNK Mitogen-Activated Protein Kinases; K619IIG2R9 / sulindac sulfone

   

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

[Title] Disseminated tuberculous myositis in a child with acute myelogenous leukemia.

We present a case of disseminated tuberculous myositis in a girl with secondary acute myelogenous Leukemia following successful chemotherapy for undifferentiated sarcoma of the maxillary sinus.

[MeSH-major] Leukemia, Myeloid, Acute / complications. Myositis / complications. Tuberculosis / complications

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(PMID = 19453083.001).

[ISSN] 1875-9572

[Journal-full-title] Pediatrics and neonatology

[ISO-abbreviation] Pediatr Neonatol

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Singapore

   

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

[Title] A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML).

[MeSH-major] Hematopoietic Stem Cell Transplantation / mortality. Leukemia, Myeloid / mortality. Leukemia, Myeloid / therapy. Myelodysplastic Syndromes / mortality. Myelodysplastic Syndromes / therapy

[MeSH-minor] Acute Disease. Adolescent. Adult. Age Distribution. Aged. Disease-Free Survival. Female. Humans. Incidence. Male. Middle Aged. Recurrence. Retrospective Studies. Survival Analysis. Tissue Donors. Transplantation, Autologous. Transplantation, Homologous. Treatment Outcome

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(PMID = 17611571.001).

[ISSN] 0887-6924

[Journal-full-title] Leukemia

[ISO-abbreviation] Leukemia

[Language] eng

[Publication-type] Comparative Study; Journal Article

[Publication-country] England

   

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

[Title] Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999-2009 in 5 hematology intensive care centers in the Czech Republic.

Acute myeloid leukemia (AML) is a severe condition with a high mortality.

The study represents a detailed analysis of the role of these factors and treatment outcomes based on a long-term follow-up of patients treated in 5 hematology intensive care centers in the Czech Republic.The studied group comprised 1,188 patients with de novo AML and 328 patients with secondary AML.

Curatively treated patients achieved fewer complete remissions and relapsed more often than those with de novo AML.

Patients with secondary AML had lower rates of allogeneic transplantation as part of consolidation therapy and a significantly shorter median overall survival.

However, the treatment outcome of de novo AML patients is not satisfactory, the only exception being those with acute promyelocytic leukemia.

[MeSH-major] Leukemia, Myeloid, Acute / mortality. Neoplasms, Second Primary / mortality

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(PMID = 20845997.001).

[ISSN] 0028-2685

[Journal-full-title] Neoplasma

[ISO-abbreviation] Neoplasma

[Language] eng

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

[Publication-country] Slovakia

   

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

[Title] Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens.

BACKGROUND: Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children.

RESULTS: Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients).

Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients.

Secondary AML/MDS developed at a median of 32 months after ALL diagnosis.

Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS.

Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation.

The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months).

CONCLUSIONS: Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / chemically induced. Myelodysplastic Syndromes / chemically induced. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy

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[Copyright] Copyright (c) 2008 American Cancer Society.

(PMID = 19090005.001).

[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

[Chemical-registry-number] 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide

[Other-IDs] NLM/ NIHMS629435; NLM/ PMC4180242

   

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

[Title] [Prognostic factor analysis of 77 old patients with acute myelogenous leukemia].

BACKGROUND & OBJECTIVE: The manifestations of old acute myelogenous (AML) patients have their special biological and clinical characteristics, with lower response rate to therapy and shorter survival time.

This study was to investigate the prognostic factors of elderly patients with AML retrospectively.

METHODS: 77 patients aged> or =60 years with AML from 1994 to 2005 were admitted to our study and all the possible prognostic factors were analyzed with Kaplan-Meier survival analysis.

The patients with primary AML (median survival time was 98 days) had significantly longer survival time than those with secondary AML (median survival time was 32 days)(P=0.007), which their CR ratios were 50% and 0% (P=0.023).

CONCLUSIONS: Factors, including age >70, PS 2 to 4, percentage of blasts in bone marrow >50%, secondary AML, unfavorable karyotype, expression of CD34, lower dosage.

[MeSH-major] Anthracyclines / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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(PMID = 16965684.001).

[Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer

[ISO-abbreviation] Ai Zheng

[Language] chi

[Publication-type] English Abstract; Journal Article

[Publication-country] China

[Chemical-registry-number] 0 / Anthracyclines; 0 / Antigens, CD34

   

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

[Title] Is there an entity of chemically induced BCR-ABL-positive chronic myelogenous leukemia?

Advances in the therapy of malignancy have been accompanied by an increased frequency of cases of secondary acute myelogenous leukemia and related clonal cytopenias and oligoblastic (subacute) myelogenous leukemia (myelodysplastic syndromes).

The acute myelogenous leukemia incidence can be increased by high-dose acute ionizing radiation exposure, alkylating agents, topoisomerase II inhibitors, possibly other DNA-damaging therapeutic agents, heavy, prolonged cigarette smoking, and high dose-time exposure to benzene, the latter less frequently seen in industrialized countries with worksite regulations.

Acute myelogenous leukemia and myelodysplastic syndromes may result from innumerable primary types of chromosome damage.

In the case of chronic myelogenous leukemia, a specific break in chromosome bands 9q34 and 22q11 must occur to result in the causal fusion oncogene (BCR-ABL).

A review of 11 studies of the chromosomal abnormalities found in presumptive cases of cytotoxic therapy-induced leukemia and of 40 studies of the subtypes of leukemia that occur following cytotoxic therapy for other cancers has not provided evidence of an increased risk for chemically induced BCR-ABL-positive chronic myelogenous leukemia.

Studies of the effects of alkylating agents, topoisomerase inhibitors, and benzene on chromosomes of hematopoietic cells in vitro, coupled with the aforementioned epidemiological studies of secondary leukemia after cytotoxic therapy or of persons exposed to high dose-time concentrations of benzene in the workplace, do not indicate a relationship among chemical exposure, injury to chromosome bands 9q34 and 22q11, and an increased risk for BCR-ABL-positive chronic myelogenous leukemia.

[MeSH-major] Antineoplastic Agents / adverse effects. Chromosome Aberrations. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / chemically induced

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(PMID = 18586919.001).

[ISSN] 1083-7159

[Journal-full-title] The oncologist

[ISO-abbreviation] Oncologist

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents

[Number-of-references] 113

   

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

[Title] Dynamic single-cell network profiles in acute myelogenous leukemia are associated with patient response to standard induction therapy.

PURPOSE: Complete response to induction chemotherapy is observed in approximately 60% of patients with newly diagnosed non-M3 acute myelogenous leukemia (AML).

However, no methods exist to predict with high accuracy at the individual patient level the response to standard AML induction therapy.

EXPERIMENTAL DESIGN: We applied single-cell network profiling (SCNP) using flow cytometry, a tool that allows a comprehensive functional assessment of intracellular signaling pathways in heterogeneous tissues, to two training cohorts of AML samples (n = 34 and 88) to predict the likelihood of response to induction chemotherapy.

Results were independent of cytogenetics, FLT3 mutational status, and diagnosis of secondary AML.

SCNP provides information distinct from other known prognostic factors such as age, secondary AML, cytogenetics, and molecular alterations and is potentially combinable with the latter to improve clinical decision making.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / metabolism

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[Copyright] Copyright 2010 AACR.

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(PMID = 20525753.001).

[ISSN] 1078-0432

[Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research

[ISO-abbreviation] Clin. Cancer Res.

[Language] eng

[Grant] United States / NCI NIH HHS / CA / P01 CA108631

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3

[Other-IDs] NLM/ NIHMS378349; NLM/ PMC3385931

   

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

[Title] Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features.

PURPOSE: Acute myelogenous leukemia (AML) does not have a high cure rate, particularly in patients with poor-risk features.

Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML.

We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR.

Comparison of CR durations for 25 patients who received two-cycle timed sequential therapy followed by tipifarnib maintenance with 23 historically similar patients who did not receive tipifarnib showed that tipifarnib was associated with DFS prolongation for patients with secondary AML and adverse cytogenetics.

CONCLUSIONS: This study suggests that some patients with poor-risk AML, including patients with secondary AML and adverse cytogenetics, may benefit from tipifarnib maintenance therapy.

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(PMID = 18483374.001).

[ISSN] 1078-0432

[Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research

[ISO-abbreviation] Clin. Cancer Res.

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / CA 69854; United States / NCI NIH HHS / CA / U01 CA069854-07; United States / NCI NIH HHS / CA / U01 CA069854; United States / NCI NIH HHS / CA / U01 CA70095; United States / NCI NIH HHS / CA / U01 CA070095

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

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Quinolones; 192185-72-1 / tipifarnib

[Other-IDs] NLM/ NIHMS281726; NLM/ PMC3074480

   

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

[Title] [Methylation status of LINE-1 sequences in patients with MDS or secondary AML].

[Transliterated title] Methylierungszustand von LINE-1-Sequenzen bei Patienten mit MDS oder sekundärer AML.

[MeSH-minor] Humans. Leukemia, Myeloid, Acute / genetics

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(PMID = 18314632.001).

[ISSN] 0070-4113

[Journal-full-title] Verhandlungen der Deutschen Gesellschaft für Pathologie

[ISO-abbreviation] Verh Dtsch Ges Pathol

[Language] ger

[Publication-type] English Abstract; Journal Article

[Publication-country] Germany

   

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

[Title] High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder.

Familial platelet disorder (FPD), a rare autosomal dominant disorder characterized by quantitative and qualitative platelet abnormalities, is considered as a model of genetic predisposition to acute myeloid leukemia (AML).

So far, monoallelic RUNX1 germline mutations have been found in 19 of 20 families with reported FPD, and the analysis of blast cells from only 5 patients at acute leukemia (AL) stage has shown no additional RUNX1 abnormality.

In addition to the germline RUNX1 mutation, we identified a second RUNX1 alteration in 6 AML cases (acquired point mutations in 4 cases and duplication of the altered RUNX1 allele associated with acquired trisomy 21 in 2 other cases).

Although haploinsufficiency of RUNX1 causes FPD, our findings suggest that a second genetic event involving RUNX1 is often associated with progression to AML.

[MeSH-major] Blood Platelet Disorders / genetics. Core Binding Factor Alpha 2 Subunit / genetics. Leukemia, Myeloid, Acute / genetics

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(PMID = 19357396.001).

[ISSN] 1528-0020

[Journal-full-title] Blood

[ISO-abbreviation] Blood

[Language] eng

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

[Publication-country] United States

[Chemical-registry-number] 0 / Core Binding Factor Alpha 2 Subunit; 0 / RUNX1 protein, human

   

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

[Title] Do children have increased susceptibility for developing secondary acute myelogenous leukemia?

This study was undertaken to evaluate the effects of age on a child's susceptibility to developing leukemia following exposure to known leukemogenic agents.

The clinical literature describing the risk of developing acute myelogenous leukemia (AML) following treatment with alkylating agents or topoisomerase reactive drugs (known leukemogens) was used as a basis for this investigation.

Although the number of studies and cases was very small, the available scientific and medical literature does not support the hypothesis that children will necessarily have an altered susceptibility or increased risk of developing chemotherapy-induced AML.

[MeSH-major] Antineoplastic Agents, Alkylating / adverse effects. Leukemia, Myeloid, Acute / epidemiology. Neoplasms, Second Primary / epidemiology

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[ErratumIn] Chem Biol Interact. 2005 Aug 15;155(3):191

(PMID = 15878160.001).

[ISSN] 0009-2797

[Journal-full-title] Chemico-biological interactions

[ISO-abbreviation] Chem. Biol. Interact.

[Language] eng

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

[Publication-country] Ireland

[Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Topoisomerase II Inhibitors

   

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

[Title] Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia.

[MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy

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(PMID = 20008642.001).

[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; Multicenter Study

[Publication-country] United States

   

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

[Title] Secondary hematological malignancies after breast cancer chemotherapy.

According to several reports, the 10 year incidence of secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after systemic chemotherapy is approximately 1.5%.

We detected 2 cases of secondary AML and 1 case of MDS, 19, 52 and 12 months, respectively, after systemic chemotherapy for breast cancer.

Published data on the occurrence of secondary hematological malignancies other than AML or MDS in this setting are scarce.

We encountered diffuse large B-cell lymphoma, angioimmunoblastic lymphoma and mantle cell lymphoma as secondary hematological malignancies after systemic chemotherapy for breast cancer.

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(PMID = 16085560.001).

[ISSN] 1042-8194

[Journal-full-title] Leukemia & lymphoma

[ISO-abbreviation] Leuk. Lymphoma

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] England

   

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

[Title] A MLL-KIAA0284 fusion gene in a patient with secondary acute myeloid leukemia and t(11;14)(q23;q32).

MLL aberrations are found in approximately 10% of acute leukemias.

We describe here the case of a patient who developed secondary acute myeloid leukemia five years after the patient had received adjuvant radiochemotherapy because of breast cancer.

The expression of KIAA0284 in various tissues and hematologic diseases was investigated by real time quantitative PCR and turned out to be very low in all lymphatic and myeloid diseases investigated.

[MeSH-major] Leukemia, Myeloid, Acute / genetics. Myeloid-Lymphoid Leukemia Protein / genetics. Neoplasms, Second Primary / genetics. Oncogene Proteins, Fusion / genetics. Translocation, Genetic

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(PMID = 18640063.001).

[ISSN] 1096-0961

[Journal-full-title] Blood cells, molecules & diseases

[ISO-abbreviation] Blood Cells Mol. Dis.

[Language] eng

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

[Publication-country] United States

[Chemical-registry-number] 0 / MLL protein, human; 0 / Oncogene Proteins, Fusion; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase

   

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

[Title] MPLW515L mutation in acute megakaryoblastic leukaemia.

A series of primary and secondary acute myeloid leukaemias (AML) with megakaryoblastic phenotype and myelofibrosis unrelated to PMF (n=12) was analysed for the MPL(W515K/L) mutation by pyrosequencing.

None of the secondary AML cases evolving from pre-existing PMF showed MPL(W515K/L) (n=4).

We conclude that MPL(W515L) occurs in a considerable proportion of acute megakaryoblastic leukaemias with myelofibrosis unrelated to PMF.

[MeSH-major] Leukemia, Megakaryoblastic, Acute / genetics. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics. Mutation / genetics. Primary Myelofibrosis / genetics. Receptors, Thrombopoietin / genetics

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[CommentIn] Leukemia. 2009 Nov;23(11):2159-60 [19657363.001]

(PMID = 19194467.001).

[ISSN] 1476-5551

[Journal-full-title] Leukemia

[ISO-abbreviation] Leukemia

[Language] eng

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

[Publication-country] England

[Chemical-registry-number] 0 / Receptors, Thrombopoietin; 143641-95-6 / MPL protein, human; EC 2.7.10.2 / JAK2 protein, human; EC 2.7.10.2 / Janus Kinase 2

   

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

[Title] Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: a report of POG study 9296.

PURPOSE: A previous Pediatric Oncology Group (POG) study showed high incidence of secondary acute myelogenous leukemia (AML) in children treated for T-cell acute lymphoblastic leukemia (T-ALL) or higher-stage lymphoblastic lymphoma.

To prevent secondary neoplasms, induce prolonged asparagine depletion, and maintain high event-free survival (EFS) in children with newly diagnosed T-ALL or higher-stage non-Hodgkins lymphoma (NHL), we designed this pilot study to determine feasibility and safety of substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase.

No patients treated entirely on this study developed secondary neoplasms.

One patient taken off study for asparaginase toxicity was treated with multiagent therapy that contained teniposide, and died from secondary myelodysplasia (sMDS)/AML.

EFS was not compromised and secondary neoplasms were decreased.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy

[MeSH-minor] Adolescent. Anthracyclines / administration & dosage. Antimetabolites, Antineoplastic / administration & dosage. Antineoplastic Agents, Alkylating / administration & dosage. Asparaginase / administration & dosage. Asparaginase / adverse effects. Child. Child, Preschool. Disease-Free Survival. Drug Hypersensitivity / etiology. Female. Follow-Up Studies. Humans. Lymphoma, Non-Hodgkin / drug therapy. Lymphoma, Non-Hodgkin / mortality. Male. Pilot Projects. Remission Induction. Sepsis / etiology. Sepsis / mortality

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(PMID = 16007607.001).

[ISSN] 1545-5009

[Journal-full-title] Pediatric blood & cancer

[ISO-abbreviation] Pediatr Blood Cancer

[Language] eng

[Grant] United States / NCI NIH HHS / CA / 5 U10 CA5312; United States / NCI NIH HHS / CA / CA29139

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

[Publication-country] United States

[Chemical-registry-number] 0 / Anthracyclines; 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents, Alkylating; EC 3.5.1.1 / Asparaginase

   

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

[Title] Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.

Amonafide-l-malate (amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML.

43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine.

Between both trials responses occurred in 9/20 patients with secondary AML.

Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Naphthalimides / administration & dosage

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[Copyright] Copyright (c) 2009 Elsevier Ltd. All rights reserved.

(PMID = 19748672.001).

[ISSN] 1873-5835

[Journal-full-title] Leukemia research

[ISO-abbreviation] Leuk. Res.

[Language] eng

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

[Publication-country] England

[Chemical-registry-number] 0 / Naphthalimides; 04079A1RDZ / Cytarabine; 1Q8D39N37L / amonafide

   

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

[Title] Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.

METHODS: We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow-biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML).

RESULTS: Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML.

There was a high frequency of FLT3 internal tandem duplications and absence of CD34 and CD133 in AML specimens with a normal karyotype and cytoplasmic dislocation of NPM, but not in those in which the protein was restricted to the nucleus.

AML specimens with cytoplasmic NPM carried mutations of the NPM gene that were predicted to alter the protein at its C-terminal; this mutant gene caused cytoplasmic localization of NPM in transfected cells.

CONCLUSIONS: Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.

[MeSH-major] Bone Marrow / pathology. Cytoplasm / chemistry. Leukemia, Myeloid, Acute / genetics. Mutation. Nuclear Proteins / genetics

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[Copyright] Copyright 2005 Massachusetts Medical Society.

[CommentIn] N Engl J Med. 2005 Jan 20;352(3):291-2 [15659732.001]

[CommentIn] N Engl J Med. 2005 Apr 28;352(17):1819-20; author reply 1819-20 [15858195.001]

[ErratumIn] N Engl J Med. 2005 Feb 17;352(7):740

(PMID = 15659725.001).

[ISSN] 1533-4406

[Journal-full-title] The New England journal of medicine

[ISO-abbreviation] N. Engl. J. Med.

[Language] eng

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

[Publication-country] United States

[Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antineoplastic Agents; 0 / Nuclear Proteins; 117896-08-9 / nucleophosmin

   

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

[Title] Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial.

[MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy

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[Cites] Mod Pathol. 2000 Feb;13(2):193-207 [10697278.001]

[Cites] Br J Haematol. 2000 Sep;110(3):620-30 [10997974.001]

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[Cites] Br J Haematol. 1982 Jun;51(2):189-99 [6952920.001]

[CommentIn] Haematologica. 2010 Oct;95(10):1623-7 [20884716.001]

(PMID = 20494931.001).

[ISSN] 1592-8721

[Journal-full-title] Haematologica

[ISO-abbreviation] Haematologica

[Language] eng

[Databank-accession-numbers] ClinicalTrials.gov/ NCT00002926

[Grant] United States / NCI NIH HHS / CA / 5U10 CA11488-32; United States / NCI NIH HHS / CA / 5U10 CA11488-27; United States / NCI NIH HHS / CA / 5U10 CA11488-38; United States / NCI NIH HHS / CA / 5U10 CA11488-28; United States / NCI NIH HHS / CA / 5U10 CA11488-35; United States / NCI NIH HHS / CA / 5U10 CA11488-31; United States / NCI NIH HHS / CA / 5U10 CA11488-26; United States / NCI NIH HHS / CA / 5U10 CA11488-37; United States / NCI NIH HHS / CA / U10 CA011488; United States / NCI NIH HHS / CA / 5U10 CA11488-29; United States / NCI NIH HHS / CA / 5U10 CA11488-36; United States / NCI NIH HHS / CA / 5U10 CA11488-33; United States / NCI NIH HHS / CA / 5U10 CA11488-34; United States / NCI NIH HHS / CA / 5U10 CA11488-30

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

[Publication-country] Italy

[Other-IDs] NLM/ PMC2948102

   

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

[Title] T-cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia.

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease.

Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers.

This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.

[MeSH-major] Antigens, Differentiation, T-Lymphocyte / analysis. Antigens, Neoplasm / analysis. Leukemia, Myeloid / pathology. Leukemia-Lymphoma, Adult T-Cell / pathology. Neoplastic Stem Cells / pathology. T-Lymphocyte Subsets / pathology

[MeSH-minor] 6-Mercaptopurine / administration & dosage. Acute Disease. Adolescent. Antigens, CD7 / analysis. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Asparaginase / administration & dosage. Bone Marrow / pathology. Cell Differentiation. Cell Lineage. Core Binding Factor Alpha 2 Subunit / genetics. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Daunorubicin / administration & dosage. Dexamethasone / administration & dosage. Diagnosis, Differential. Doxorubicin / administration & dosage. Etoposide / administration & dosage. Etoposide / adverse effects. Fatal Outcome. Female. Gene Dosage. Histone-Lysine N-Methyltransferase. Humans. Immunophenotyping. Karyotyping. Methotrexate / administration & dosage. Myeloid-Lymphoid Leukemia Protein / genetics. Neoplasms, Second Primary / diagnosis. Proto-Oncogenes. Recurrence. Vincristine / administration & dosage

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[Copyright] (c) 2006 Wiley-Liss, Inc.

(PMID = 16206214.001).

[ISSN] 1545-5009

[Journal-full-title] Pediatric blood & cancer

[ISO-abbreviation] Pediatr Blood Cancer

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antigens, CD7; 0 / Antigens, Differentiation, T-Lymphocyte; 0 / Antigens, Neoplasm; 0 / Core Binding Factor Alpha 2 Subunit; 0 / MLL protein, human; 0 / RUNX1 protein, human; 04079A1RDZ / Cytarabine; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; E7WED276I5 / 6-Mercaptopurine; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase; EC 3.5.1.1 / Asparaginase; YL5FZ2Y5U1 / Methotrexate; ZS7284E0ZP / Daunorubicin

   

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

[Title] Secondary acute myeloid leukemia after etoposide therapy for retinoblastoma.

Most chemotherapy regimens used in retinoblastoma include etoposide, an epipodophyllotoxin associated with a risk of secondary myeloid leukemia.

The use of etoposide in patients with a cancer predisposition syndrome such as retinoblastoma is potentially harmful, however, reports of secondary acute myeloid leukemia in patients treated with etoposide for retinoblastoma are rare.

We report a case of a patient who developed secondary acute myeloid leukemia after etoposide treatment for retinoblastoma.

[MeSH-major] Antineoplastic Agents, Phytogenic / adverse effects. Etoposide / adverse effects. Leukemia, Myeloid / chemically induced. Leukemia, Myeloid / diagnosis. Retinal Neoplasms / drug therapy. Retinoblastoma / drug therapy

[MeSH-minor] Acute Disease. Female. Humans. Infant. Treatment Outcome

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[ErratumIn] J Pediatr Hematol Oncol. 2007 Oct;29(10):728. Pèer, Jacob [corrected to Pe'er, Jacob]

(PMID = 17805043.001).

[ISSN] 1077-4114

[Journal-full-title] Journal of pediatric hematology/oncology

[ISO-abbreviation] J. Pediatr. Hematol. Oncol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 6PLQ3CP4P3 / Etoposide

   

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

Enhanced bone marrow (BM) angiogenesis is regarded as an essential cofactor in the progression of MDS to acute myelogenous leukemia (AML) and microvessel formation may be induced by TNF-alpha as well.

METHODS: TNF-alpha expression and BM vessels were immunohistochemically analyzed on 89 paraffin-embedded BM biopsies from patients with MDS and secondary AML, including 12 control samples.

MVD was increased in MDS and secondary AML and correlated with marrow cellularity and expression of TNF-alpha, but was not of prognostic significance.

CONCLUSIONS: TNF-alpha expression and MVD are elevated in MDS and secondary AML.

[MeSH-major] Biomarkers, Tumor / biosynthesis. Erythroid Precursor Cells / metabolism. Gene Expression Regulation, Leukemic. Leukemia, Myeloid, Acute / metabolism. Myelodysplastic Syndromes / metabolism. Tumor Necrosis Factor-alpha / biosynthesis

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(PMID = 16313260.001).

[ISSN] 0902-4441

[Journal-full-title] European journal of haematology

[ISO-abbreviation] Eur. J. Haematol.

[Language] eng

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

[Publication-country] Denmark

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Tumor Necrosis Factor-alpha

   

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

[Title] A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia.

PURPOSE: Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents.

We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy.

EXPERIMENTAL DESIGN: We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML.

Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response.

[MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Sirolimus / administration & dosage

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(PMID = 19843663.001).

[ISSN] 1078-0432

[Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research

[ISO-abbreviation] Clin. Cancer Res.

[Language] eng

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

[Publication-country] United States

[Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; EC 2.7.- / Protein Kinases; EC 2.7.1.1 / MTOR protein, human; EC 2.7.1.1 / TOR Serine-Threonine Kinases; Q41OR9510P / Melphalan; W36ZG6FT64 / Sirolimus; MEC regimen

   

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

[Title] Secondary acute myeloid leukemia - a single center experience.

Secondary acute myeloid leukemia (sAML) may arise from the previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome (MDS) or from chronic myeloproliferative neoplasia (cMPN) or after exposure to a leukemogenic agent (previous chemotherapy or radiotherapy, some immunosuppressive drugs or environmental leukemogenic agents).

Secondary origin of AML is associated with unfavorable prognosis and it is not considered to be conventionally curable (with the exception of secondary acute promyelocytic leukemia).

Over that period of time, a total 574 patients with AML were diagnosed.

Of those, 430 patients were diagnosed as having primary AML; in 86 patients, sAML transformed from myelodysplastic syndrome and 58 patients were followed or treated for various malignancies or were treated with potentially leukemogenic agents because of non-malignant disorders.

Patients with secondary AML are older and less commonly treated with curative intention than those with primary AML.

With the exception of secondary acute promyelocytic leukemia, the prognosis of which does not differ from very good prognosis of the primary forms, secondary AML is not considered a conventionally curable disease.

[MeSH-major] Leukemia, Myeloid, Acute / etiology. Myelodysplastic Syndromes / complications. Myeloproliferative Disorders / complications. Neoplasm Recurrence, Local / etiology. Neoplasms, Second Primary / etiology

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(PMID = 20099982.001).

[ISSN] 0028-2685

[Journal-full-title] Neoplasma

[ISO-abbreviation] Neoplasma

[Language] eng

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

[Publication-country] Slovakia

   

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

[Title] Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia.

In a phase I study of flavopiridol followed by 1-beta-d-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31%.

We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML.

Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML.

CONCLUSIONS: Flavopiridol has anti-AML activity directly and in combination with ara-C and mitoxantrone.

This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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(PMID = 17671131.001).

[ISSN] 1078-0432

[Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research

[ISO-abbreviation] Clin. Cancer Res.

[Language] eng

[Grant] United States / NCRR NIH HHS / RR / M01-RR0052; United States / NCI NIH HHS / CA / U01 CA70095

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

[Publication-country] United States

[Chemical-registry-number] 0 / Flavonoids; 0 / Piperidines; 04079A1RDZ / Cytarabine; 45AD6X575G / alvocidib; BZ114NVM5P / Mitoxantrone

   

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

[Title] Oxaliplatin-related acute myelogenous leukemia.

Bone marrow biopsy was consistent with therapy-related acute myelogenous leukemia.

It is likely that the leukemia was related to the oxaliplatin administration.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Leukemia, Myeloid, Acute / chemically induced

[MeSH-minor] Adenocarcinoma / drug therapy. Adenocarcinoma / pathology. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Humanized. Bevacizumab. Cecal Neoplasms / drug therapy. Cecal Neoplasms / pathology. Chromosome Deletion. Female. Fluorouracil / administration & dosage. Fluorouracil / adverse effects. Humans. Leucovorin / administration & dosage. Leucovorin / adverse effects. Middle Aged. Omentum / pathology. Organoplatinum Compounds / administration & dosage. Organoplatinum Compounds / adverse effects. Ovarian Neoplasms / drug therapy. Ovarian Neoplasms / secondary. Peritoneal Neoplasms / drug therapy. Peritoneal Neoplasms / secondary. Sigmoid Neoplasms / drug therapy. Sigmoid Neoplasms / secondary. Trisomy

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(PMID = 16549810.001).

[ISSN] 1083-7159

[Journal-full-title] The oncologist

[ISO-abbreviation] Oncologist

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Organoplatinum Compounds; 2S9ZZM9Q9V / Bevacizumab; Q573I9DVLP / Leucovorin; U3P01618RT / Fluorouracil; Folfox protocol

   

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

[Title] Secondary acute myeloid leukemia early after therapy for Hodgkin's disease--a case report.

A case of acute myeloid leukemia (AML) after successful therapy for Hodgkin's disease (HD) is reported.

Seven months after the CR was obtained the patient developed AML.

Knowing that the prognosis of patients with secondary AML (sAML) after primary HD is poor we decided to perform autologous peripheral stem cells' transplantation.

[MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / diagnosis. Leukemia, Myeloid, Acute / surgery. Neoplasms, Second Primary / diagnosis. Neoplasms, Second Primary / surgery

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(PMID = 17918297.001).

[ISSN] 1107-0625

[Journal-full-title] Journal of B.U.ON. : official journal of the Balkan Union of Oncology

[ISO-abbreviation] J BUON

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Greece

   

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

[Title] Unrelated donor bone marrow transplantation using a chemotherapy-only preparative regimen for adults with high-risk acute myelogenous leukemia.

Limited data are available for adults undergoing unrelated donor (URD) BMT for AML using chemotherapy-only preparative regimens.

Previous studies incorporated irradiation, included adults and children, and excluded secondary leukemia.

Herein we report long-term outcomes for adults with poor-prognostic AML receiving a novel regimen of busulfan (16 mg/kg), cytarabine (8,000 mg/m(2)), and cyclophosphamide (120 mg/kg) (BAC), followed by URD BMT.

Adverse features included unfavorable cytogenetics (49%), secondary AML (47%), leukemia at transplant (42%), and extramedullary disease (16%).

At time of BMT, 23 were in remission (12 CR1) while 22 had leukemia.

Acute and chronic GVHD rates were 44 and 67%, respectively.

Seventeen (38%) were disease-free 52 months post-BMT; 13 were leukemia-free (eight CR1) at transplant.

Secondary leukemia, cytogenetics, cell dose, and GVHD did not influence outcome.

In poor-risk AML, BAC provided cytoreduction comparable to reported TBI-containing regimens, when administered for URD BMT.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Bone Marrow Transplantation. Leukemia, Myeloid, Acute / therapy. Tissue Donors. Transplantation Conditioning

[MeSH-minor] Acute Disease. Adult. Chronic Disease. Disease-Free Survival. Doxorubicin / administration & dosage. Doxorubicin / adverse effects. Factor XIII / administration & dosage. Factor XIII / adverse effects. Female. Fibrinogen / administration & dosage. Fibrinogen / adverse effects. Follow-Up Studies. Graft vs Host Disease / etiology. Graft vs Host Disease / mortality. Humans. Male. Middle Aged. Recurrence. Remission Induction. Retrospective Studies. Thrombin / administration & dosage. Thrombin / adverse effects. Transplantation, Homologous

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(PMID = 16986128.001).

[ISSN] 0361-8609

[Journal-full-title] American journal of hematology

[ISO-abbreviation] Am. J. Hematol.

[Language] eng

[Publication-type] Clinical Trial; Comparative Study; Journal Article

[Publication-country] United States

[Chemical-registry-number] 80168379AG / Doxorubicin; 9001-32-5 / Fibrinogen; 9013-56-3 / Factor XIII; EC 3.4.21.5 / Thrombin; bio-adhesio-chemo protocol

   

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

[Title] Acute myelogenous leukemia and myelodysplasia secondary to breast cancer treatment: case studies and literature review.

BACKGROUND AND PURPOSE: Chemotherapy and radiation therapy for breast cancer are known to increase the risk of developing a myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML).

Radiation therapy adds to the risk, and there is speculation that granulocyte colony-stimulating factor (G-CSF) may also predispose to leukemia.

The purpose of this systemic review is to bring to the attention of family physicians the unintended consequence of leukemia secondary to aggressively treated breast cancer.

METHODS: The medical records of several patients from Robert Wood Johnson University Hospital, with previously treated breast cancer admitted for therapy for AML or myelodysplasia, were reviewed.

RESULTS: Cases of patients whose AML was likely secondary to their treatment for breast cancer were used to illustrate the role of chemotherapy, radiation therapy, and perhaps G-CSF in the development of leukemia.

CONCLUSIONS: Chemotherapy and radiation therapy administered for breast cancer predispose patients to the development of MDS or AML.

We hypothesize that the breast cancer (BRCA) gene mutations might add to the risk and that primary care physicians must be aware of the long-term risks of cytotoxic therapy, including the development of MDS or AML.

[MeSH-major] Breast Neoplasms / drug therapy. Breast Neoplasms / radiotherapy. Leukemia, Myeloid, Acute / etiology. Myelodysplastic Syndromes / etiology

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(PMID = 19996729.001).

[ISSN] 1538-2990

[Journal-full-title] The American journal of the medical sciences

[ISO-abbreviation] Am. J. Med. Sci.

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating

[Number-of-references] 28

   

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

[Title] Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia.

PURPOSE: The risk factors for treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (AML) after autologous stem-cell transplantation (ASCT) are similar to those that increase the risk of difficult stem-cell harvests.

We reviewed our experience in 526 patients with lymphoma treated by ASCT to determine whether difficult stem-cell harvests predict for an increased risk of t-MDS/AML.

RESULTS: With a median follow-up time for surviving patients of 69 months, 20 patients developed t-MDS/AML, for an actuarial incidence of 6.8% at 10 years.

Pretransplantation characteristics, including age, diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, bone marrow involvement, prior radiation therapy, prior exposure to chemotherapy, lactate dehydrogenase at the time of ASCT, disease status, and method of stem-cell mobilization, were then analyzed with respect to the subsequent development of t-MDS/AML.

By multivariable analysis, prior exposure to radiation therapy, four or more chemotherapy regimens, and more than 5 days of apheresis needed to harvest enough stem cells were identified as independent risk factors for t-MDS/AML.

CONCLUSION: These results suggest that identifiable pretransplantation factors predict for t-MDS/AML after ASCT.

[MeSH-major] Leukemia, Myeloid, Acute / etiology. Lymphoma / surgery. Myelodysplastic Syndromes / etiology. Peripheral Blood Stem Cell Transplantation

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(PMID = 16877727.001).

[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

[Chemical-registry-number] 143011-72-7 / Granulocyte Colony-Stimulating Factor

   

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

The myelodysplastic syndromes are a group of heterogeneous acquired and clonal disorders that are characterized by the intramedullar, abnormal death of myeloid progenitors leading to peripheral variable cytopenias.

It is predictive for the risk of transformation in secondary acute myeloid leukemia.

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(PMID = 21425539.001).

[ISSN] 0035-2640

[Journal-full-title] La Revue du praticien

[ISO-abbreviation] Rev Prat

[Language] fre

[Publication-type] English Abstract; Journal Article

[Publication-country] France

   

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

[Title] RUNX1 amplification in lineage conversion of childhood B-cell acute lymphoblastic leukemia to acute myelogenous leukemia.

Amplification of RUNX1 (alias AML1) is a recurrent karyotypic abnormality in childhood acute lymphoblastic leukemia (ALL) that is generally associated with a poor outcome.

It does not occur with other primary chromosomal abnormalities in acute ALL.

AML1 amplification in acute myelogenous leukemia (AML) is a rare secondary event described mainly in therapy-related cases.

AML1 amplification was found in a 13-year-old patient with AML M4/M5 leukemia that occurred 5 years after she had been diagnosed with common B-cell ALL.

Conventional cytogenetic, fluorescent in situ hybridization (FISH), and polymerase chain reaction methods revealed no other chromosomal change expected to occur in a disease that we assumed to be a secondary leukemia.

[MeSH-major] Core Binding Factor Alpha 2 Subunit / genetics. Gene Expression Regulation, Neoplastic. Leukemia, B-Cell / genetics. Leukemia, B-Cell / pathology. Leukemia, Myeloid, Acute / genetics. Leukemia, Myeloid, Acute / pathology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

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(PMID = 17889714.001).

[ISSN] 0165-4608

[Journal-full-title] Cancer genetics and cytogenetics

[ISO-abbreviation] Cancer Genet. Cytogenet.

[Language] eng

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

[Publication-country] United States

[Chemical-registry-number] 0 / Core Binding Factor Alpha 2 Subunit; 0 / RUNX1 protein, human

   

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

[Title] Is secondary leukemia an independent poor prognostic factor in acute myeloid leukemia?

Secondary leukemia is a poorly defined term that often refers to the development of acute myeloid leukemia (AML) following the history of a previous disease, such as a myelodysplastic syndrome or a chronic myeloproliferative disorder.

Secondary leukemia can also be a consequence of treatment with chemotherapy, including alkylating agents and topoisomerase II inhibitors, and/or radiotherapy, or due to exposure to environmental carcinogens.

Outcomes for this large and variable group of patients with secondary AML have been poor compared to people who develop AML de novo.

The question arises whether a diagnosis of secondary leukemia per se indicates a poor prognosis or whether their bad outcomes result from an association with certain morphologic and biologic characteristics.

Morphologic dysplasia in de novo AML is related to unfavorable cytogenetics, but has no independent prognostic relevance under the conditions of intensive chemotherapy.

While there is no significant correlation between cytogenetic risk groups and dysplasia, cytogenetic features do have an impact on outcome among both de novo and secondary AML patients.

In various subgroups of secondary AML, the spectrum of cytogenetic abnormalities is similar to de novo AML, but the frequency of abnormalities associated with unfavorable and intermediate risk cytogenetics, such as a complex karyotype, trisomy 8, monosomy 7, and others, is higher in secondary AML.

The survival of patients with therapy-related myeloid leukemia (t-AML) is generally shorter than for those with de novo AML within the same cytogenetic risk group.

Across the population of t-AML, however, survival varies according to cytogenetic risk group, with longer survival in patients with favorable-risk karyotypes.

The term secondary AML is too broad and imprecise to be of importance and should not be used.

These AML patients should be enrolled on front-line chemotherapy trials and should be stratified by pretreatment disease status and exposure history, if necessary.

[MeSH-major] Chromosome Aberrations. Leukemia, Myeloid / drug therapy. Leukemia, Myeloid / genetics

[MeSH-minor] Acute Disease. Humans. Myelodysplastic Syndromes. Myeloproliferative Disorders. Neoplasms, Second Primary / drug therapy. Neoplasms, Second Primary / genetics. Prognosis. Survival Analysis

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(PMID = 17336252.001).

[ISSN] 1521-6926

[Journal-full-title] Best practice & research. Clinical haematology

[ISO-abbreviation] Best Pract Res Clin Haematol

[Language] eng

[Publication-type] Journal Article; Review

[Publication-country] England

[Number-of-references] 23

   

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

Three cases were diagnosed as polycythemia vera; one case presented with secondary acute myeloid leukemia following idiopathic osteomyelofibrosis.

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(PMID = 15993276.001).

[ISSN] 0165-4608

[Journal-full-title] Cancer genetics and cytogenetics

[ISO-abbreviation] Cancer Genet. Cytogenet.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

   

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

Here we report, for the first time, the isolation of a highly daptomycin-resistant strain of Corynebacterium jeikeium causing a life-threatening infection in a neutropenic patient undergoing cord blood transplantation for secondary acute myeloid leukemia.

[MeSH-minor] Cord Blood Stem Cell Transplantation / adverse effects. Humans. Leukemia, Myeloid, Acute / complications. Male. Microbial Sensitivity Tests. Middle Aged

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(PMID = 19420177.001).

[ISSN] 1098-660X

[Journal-full-title] Journal of clinical microbiology

[ISO-abbreviation] J. Clin. Microbiol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / Anti-Bacterial Agents; NWQ5N31VKK / Daptomycin

[Other-IDs] NLM/ PMC2708472

   

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

[Title] An unusual case of myelodysplastic syndrome with prolonged clonal stability, indolent clinical course over a decade, and spontaneous regression of AML in the terminal phase.

An unusual case of secondary acute myeloid leukemia (AML) with indolent clinical course is described.

In 2001, transformation to secondary AML with an increase in bone marrow blasts (>20%) and thrombocytopenia, was found.

However, the bone marrow still showed AML with >20% blasts.

[MeSH-major] Leukemia, Myeloid, Acute / physiopathology. Myelodysplastic Syndromes / complications

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[Copyright] (c) Blackwell Munksgaard 2005.

(PMID = 15946315.001).

[ISSN] 0902-4441

[Journal-full-title] European journal of haematology

[ISO-abbreviation] Eur. J. Haematol.

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Denmark

[Chemical-registry-number] 0 / Receptors, Androgen

   

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

[Title] Multiple hepatocellular carcinomas developed 15 months after commencement of chemotherapy for elderly acute myelogenous leukemia.

In May 2006, a 72-year-old man with acute myelogenous leukemia (M4Eo) was admitted to our hospital.

He received chemotherapy according to the JALSG GML200 protocol, which led to complete remission; however, in January 2007, his leukemia recurred.

He eventually died because of aggressive enlargement of liver tumors during the following month accompanied by the simultaneous recurrence of leukemia and unsuccessful embolization of the hepatic artery.

Autopsy specimens showed fibrosis and considerable iron deposition in the liver, suggested secondary hemochromatosis due to transfusion.

Secondary hemochromatosis, androgen imbalance, and humoral factors from leukemic cells were believed to be the causes of the rapid onset and development of HCCs.

[MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular. Leukemia, Myeloid, Acute / drug therapy. Liver Neoplasms. Neoplasms, Second Primary

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(PMID = 20009436.001).

[ISSN] 0485-1439

[Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology

[ISO-abbreviation] Rinsho Ketsueki

[Language] eng

[Publication-type] Case Reports; Journal Article

[Publication-country] Japan

[Chemical-registry-number] 0 / Androgen Antagonists; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 74KXF8I502 / Aclarubicin; CAG protocol