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1. Ho AD, Suciu S, Stryckmans P, De Cataldo F, Willemze R, Thaler J, Peetermans M, Döhner H, Solbu G, Dardenne M, Zittoun R: Pentostatin (Nipent) in T-cell malignancies. Leukemia Cooperative Group and the European Organization for Research and Treatment of Cancer. Semin Oncol; 2000 Apr;27(2 Suppl 5):52-7
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  • [Title] Pentostatin (Nipent) in T-cell malignancies. Leukemia Cooperative Group and the European Organization for Research and Treatment of Cancer.
  • Within this phase II trial of the European Organization for Research and Treatment of Cancer, we have investigated the safety and efficacy of pentostatin (Nipent; SuperGen, San Ramon, CA) in refractory lymphoid malignancies.
  • Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then every 14 days, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months.
  • We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia, and hairy cell leukemia This report focuses on the outcome in T-cell malignancies: T-cell chronic lymphocytic leukemia, Sézary syndrome, mycosis fungoides, and T-zone lymphoma.
  • Of 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, ie, 25 of 28 with T-cell chronic lymphocytic leukemia, 21 of 26 with Sézary syndrome, 22 of 26 with mycosis fungoides, and eight of 12 with T-zone lymphoma.
  • All patients had progressive and advanced disease.
  • Sixteen patients (21%) died during the first 9 weeks of treatment: 12 of progressive disease, two of infectious complications thought to be unrelated to treatment, one of myocardial infarction, and one of renal failure related to administration of intravenous contrast.
  • Better results were achieved in patients with Sézary syndrome or mycosis fungoides (complete remission + partial remission = 33.4% and 22.7%, respectively) than in patients with T-cell chronic lymphocytic leukemia (8%) or T-zone lymphoma (25%).
  • We conclude that pentostatin is active in low-grade T-cell malignancies.
  • A higher dose might be necessary for some T-cell malignancies.
  • [MeSH-major] Antibiotics, Antineoplastic / therapeutic use. Immunosuppressive Agents / therapeutic use. Leukemia, T-Cell / drug therapy. Lymphoma, T-Cell / drug therapy. Pentostatin / therapeutic use
  • [MeSH-minor] Adult. Aged. Cause of Death. Disease Progression. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Humans. Leukemia, Hairy Cell / drug therapy. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Prolymphocytic / drug therapy. Male. Middle Aged. Mycosis Fungoides / drug therapy. Remission Induction. Sezary Syndrome / drug therapy. Skin Neoplasms / drug therapy. Treatment Outcome

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  • (PMID = 10877053.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Immunosuppressive Agents; 395575MZO7 / Pentostatin
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2. Smith KJ, Welsh M, Skelton H: Trichophyton rubrum showing deep dermal invasion directly from the epidermis in immunosuppressed patients. Br J Dermatol; 2001 Aug;145(2):344-8
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  • Trichophyton rubrum is the most widely encountered dermatophyte infection, and is usually regarded as exclusively keratinophilic often leading to chronic cutaneous and nail infections, even in healthy individuals.
  • We present three patients with acute leukaemias, with ill-defined pre-existent cutaneous eruptions that were treated with a potent topical corticosteroid.
  • All three patients received aggressive marrow toxic chemotherapy.
  • These patients had progression of their cutaneous disease, which showed deep dermal invasion of T. rubrum, invading directly from the epidermis with no evidence of systemic spread.
  • [MeSH-minor] Adolescent. Adult. Amphotericin B / therapeutic use. Anti-Inflammatory Agents / therapeutic use. Antifungal Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Fluconazole / therapeutic use. Humans. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / immunology. Leukemia, Promyelocytic, Acute / drug therapy. Leukemia, Promyelocytic, Acute / immunology. Male. Middle Aged. Naphthalenes / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology. Steroids. Treatment Outcome. Trichophyton / immunology

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  • (PMID = 11531807.001).
  • [ISSN] 0007-0963
  • [Journal-full-title] The British journal of dermatology
  • [ISO-abbreviation] Br. J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Antifungal Agents; 0 / Naphthalenes; 0 / Steroids; 7XU7A7DROE / Amphotericin B; 8VZV102JFY / Fluconazole; G7RIW8S0XP / terbinafine
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3. Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA, Rezvani K, Craddock C, Rassam S, Prentice HG: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant. Br J Haematol; 2001 Dec;115(3):622-9
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  • [Title] Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
  • Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics.
  • Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control.
  • We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor.
  • Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one.
  • Actuarial overall survival was 60% and disease-free survival was 26% at 58 months.
  • Transplants were well tolerated with no treatment-related deaths.
  • The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this.
  • FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Bone Marrow Transplantation. Cytarabine / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Idarubicin / administration & dosage. Leukemia / therapy. Transplantation Conditioning / methods. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives
  • [MeSH-minor] Acute Disease. Adult. Anemia, Refractory, with Excess of Blasts / therapy. Child. Child, Preschool. Disease-Free Survival. Female. Filgrastim. Graft vs Host Disease / immunology. Graft vs Host Disease / prevention & control. Humans. Leukemia, Myeloid / therapy. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recombinant Proteins. Recurrence. Reoperation. Retrospective Studies. Survival Rate. Transplantation, Homologous

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  • (PMID = 11736947.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; PVI5M0M1GW / Filgrastim; ZRP63D75JW / Idarubicin; Ida-FLAG protocol
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4. Rousseau RF, Bollard CM, Heslop HE: Gene therapy for paediatric leukaemia. Expert Opin Biol Ther; 2001 Jul;1(4):663-74
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  • [Title] Gene therapy for paediatric leukaemia.
  • Improvements in the chemotherapeutic and transplant regimens have had a significant impact in improving survival rates for paediatric leukaemia.
  • However, there are still important problems to address including what options are available for patients with chemoresistant disease and what strategies are available to avoid the concerns regarding the toxicity associated with highly cytotoxic treatment regimens.
  • Gene therapy and immunotherapy protocols hold great promise.
  • Using gene transfer of a marker gene, a number of biological issues in the therapy of leukaemia have been addressed.
  • For example, by gene marking autologous bone marrow grafts it has been possible to demonstrate that infused marrow contributes to relapse in acute and chronic myeloid leukaemias.
  • In the allogeneic transplant setting, genetically modified T-cells have proven valuable for the prophylaxis and treatment of viral diseases and may have an important role in preventing or treating disease relapse.
  • Gene transfer is also being used to modify tumour function, enhance immunogenicity, and confer drug-resistance to normal haematopoietic stem cells.
  • With the continued scientific advancements in this field, gene therapy will almost certainly have a major impact on the treatment of paediatric leukaemia in the future.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Genetic Therapy / methods. Leukemia / therapy
  • [MeSH-minor] Child. Clinical Trials, Phase I as Topic. Dendritic Cells / immunology. Dendritic Cells / metabolism. Gene Transfer Techniques. Genes, MDR. Genetic Vectors. Hematopoietic Stem Cell Transplantation. Hematopoietic Stem Cells / physiology. Humans. Immunotherapy / methods. Immunotherapy, Adoptive. Oncogenes

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  • (PMID = 11727502.001).
  • [ISSN] 1471-2598
  • [Journal-full-title] Expert opinion on biological therapy
  • [ISO-abbreviation] Expert Opin Biol Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Cancer Vaccines
  • [Number-of-references] 139
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5. Kuroda J, Kimura S, Andreeff M, Ashihara E, Kamitsuji Y, Yokota A, Kawata E, Takeuchi M, Tanaka R, Murotani Y, Matsumoto Y, Tanaka H, Strasser A, Taniwaki M, Maekawa T: ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. Br J Haematol; 2008 Jan;140(2):181-90
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  • [Title] ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms.
  • ABT-737 potently induced apoptosis in Bcr-Abl(+) chronic myeloid leukaemia (CML) cell lines and primary CML samples in vitro and prolonged the survival of mice xenografted with BV173 cells, a CML cell line.
  • Higher expression of anti-apoptotic Bcl-2 proteins reduced cell killing by ABT-737 in each cell line, but there was no correlation between the sensitivities to ABT-737 and the specific expression patterns of Bcl-2 family proteins among cell lines.
  • Thus, the cell killing effect of ABT-737 must be determined not only by the expression patterns of Bcl-2 family proteins but also by other mechanisms, such as high expression of Bcr-Abl, or a drug-efflux pump, in CML cells.
  • ABT-737 augmented the cell killing effect of imatinib in Bcr-Abl(+) cells with diverse drug-resistance mechanisms unless leukaemic cells harboured imatinib-insensitive Abl kinase domain mutations, such as T315I.
  • These results suggest that ABT-737 is a useful component of chemotherapies for CML with diverse drug-resistance mechanisms.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Biphenyl Compounds / pharmacology. Drug Resistance, Neoplasm. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. Nitrophenols / pharmacology. Sulfonamides / pharmacology
  • [MeSH-minor] Animals. Antineoplastic Agents, Phytogenic / pharmacology. Antineoplastic Combined Chemotherapy Protocols / pharmacology. Apoptosis / drug effects. Dose-Response Relationship, Drug. Drug Evaluation, Preclinical. Harringtonines / pharmacology. Humans. Male. Mice. Mice, Inbred NOD. Mice, SCID. Neoplasm Transplantation. Piperazines / pharmacology. Piperazines / therapeutic use. Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors. Survival Analysis. Transplantation, Heterologous. Tumor Cells, Cultured

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  • (PMID = 18028486.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P01 CA49639; United States / NCI NIH HHS / CA / P01 CA55164
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / ABT-737; 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Phytogenic; 0 / Biphenyl Compounds; 0 / Harringtonines; 0 / Nitrophenols; 0 / Piperazines; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Sulfonamides; 6FG8041S5B / homoharringtonine
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6. Kreitman RJ: Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies. Curr Pharm Des; 2009;15(23):2652-64
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  • [Title] Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies.
  • No agents of this class are approved yet for medical use, although a related molecule, denileukin diftitox, composed of interleukin-2 fused to truncated diphtheria toxin, is approved for relapsed/refractory cutaneous T-cell lymphoma.
  • Recombinant immunotoxins which have been tested in patients with chemotherapy-pretreated hematologic malignancies include LMB-2 (anti-CD25), BL22 (CAT-3888, anti-CD22) and HA22 (CAT-8015, anti-CD22), each containing an Fv fragment fused to truncated Pseudomonas exotoxin.
  • Major responses were observed with LMB-2 in adult T-cell leukemia, chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma, Hodgkin's disease, and hairy cell leukemia (HCL).
  • HA22, an improved version of BL22 with higher affinity to CD22, is now undergoing phase I testing in HCL, CLL, non-Hodgkin's lymphoma, and pediatric acute lymphoblastic leukemia.
  • [MeSH-major] Drug Discovery / methods. Drug Resistance, Neoplasm / drug effects. Hematologic Neoplasms / drug therapy. Immunotoxins / therapeutic use. Recombinant Proteins / therapeutic use

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  • (PMID = 19689336.001).
  • [ISSN] 1873-4286
  • [Journal-full-title] Current pharmaceutical design
  • [ISO-abbreviation] Curr. Pharm. Des.
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Diphtheria Toxin; 0 / Immunotoxins; 0 / Leukocidins; 0 / Pseudomonas aeruginosa Cytotoxins; 0 / Recombinant Proteins; 0 / Toxins, Biological
  • [Number-of-references] 190
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7. Fujino Y, Sawamura S, Kurakawa N, Hisasue M, Masuda K, Ohno K, Tsujimoto H: Treatment of chronic lymphocytic leukaemia in three dogs with melphalan and prednisolone. J Small Anim Pract; 2004 Jun;45(6):298-303
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  • [Title] Treatment of chronic lymphocytic leukaemia in three dogs with melphalan and prednisolone.
  • Three adult dogs with chronic lymphocytic leukaemia (CLL) were successfully treated with melphalan and prednisolone.
  • Based on the immunophenotypic analysis of leukaemic cells, two dogs were diagnosed with B cell CLL and one dog was tentatively diagnosed as having T cell CLL.
  • One dog with B cell CLL had IgM monoclonal gammopathy.
  • The clinical signs and haematological abnormalities associated with CLL in the three dogs improved with the administration of cytoreductive melphalan (3 to 5 mg/m2/day) and prednisolone (4.3 to 30 mg/m2/day) for eight to 210 days.
  • Melphalan and prednisolone therapy may achieve remission with few side effects in dogs with CLL.
  • [MeSH-major] Antineoplastic Agents, Alkylating / administration & dosage. Dog Diseases / drug therapy. Glucocorticoids / administration & dosage. Leukemia, Lymphocytic, Chronic, B-Cell / veterinary. Melphalan / administration & dosage. Prednisolone / administration & dosage
  • [MeSH-minor] Animals. Blood Cell Count / veterinary. Blood Chemical Analysis / veterinary. Blood Platelets. Diagnosis, Differential. Dogs. Drug Therapy, Combination. Female. Lymphocytes. Male

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  • (PMID = 15206475.001).
  • [ISSN] 0022-4510
  • [Journal-full-title] The Journal of small animal practice
  • [ISO-abbreviation] J Small Anim Pract
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Glucocorticoids; 9PHQ9Y1OLM / Prednisolone; Q41OR9510P / Melphalan
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8. Singleton CL, Wack RF, Zabka TS, Kent MS, Larsen RS: Diagnosis and treatment of chronic T-lymphocytic leukemia in a spotted hyena (Crocuta crocuta). J Zoo Wildl Med; 2007 Sep;38(3):488-91
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  • [Title] Diagnosis and treatment of chronic T-lymphocytic leukemia in a spotted hyena (Crocuta crocuta).
  • The morphology and distribution of neoplastic T-lymphocytes within the spleen, liver, peripheral blood, and bone marrow was most consistent with chronic T-lymphocytic leukemia.
  • Treatment with chlorambucil and prednisone effectively decreased the lymphocyte count, but was associated with thrombocytopenia, which resolved after chlorambucil treatment was temporarily discontinued.
  • Chemotherapy was resumed with a single dose of L-asparaginase, followed by a lower dosage of chlorambucil and continued prednisone.
  • Two years after initial diagnosis, the hyena developed a hemoabdomen and was euthanized.
  • Neoplastic T-lymphocytes were present in spleen, liver, visceral and peripheral lymph nodes, lungs, heart, kidney, adrenal glands, mesentery, intestines, pancreas, brain, and bone marrow.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Hyaenidae. Leukemia, T-Cell / veterinary
  • [MeSH-minor] Animals. Fatal Outcome. Female. Neoplasm Metastasis. Treatment Outcome

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  • (PMID = 17939362.001).
  • [ISSN] 1042-7260
  • [Journal-full-title] Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians
  • [ISO-abbreviation] J. Zoo Wildl. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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9. Malani AK, Gupta C, Rangineni R, Singh J, Ammar H: Concomitant presentation of acute myeloid leukemia with T-cell large granular lymphocytic leukemia. Acta Oncol; 2007;46(2):247-9
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  • [Title] Concomitant presentation of acute myeloid leukemia with T-cell large granular lymphocytic leukemia.
  • T-cell large granular lymphocyte leukemia (T-LGL) also known as T-cell chronic lymphocytic leukemia is rare and comprises a small minority of all small lymphocytic leukemias.
  • The concomitant presentation of T-LGL with acute myeloid leukemia (AML) has not been previously reported.
  • We present an elderly gentleman with concomitant T-LGL and AML (non-M3) diagnosed by a combination of morphologic evaluation, immunophenotyping by flow cytometry, and T-cell gene rearrangement studies.
  • The patient was managed with combination AML chemotherapy.
  • He remains alive and well seven months after initial diagnosis.
  • [MeSH-major] Leukemia, Myeloid / diagnosis. Leukemia, Prolymphocytic, T-Cell / diagnosis
  • [MeSH-minor] Acute Disease. Aged, 80 and over. Antigens, CD / analysis. Flow Cytometry. Humans. Male

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  • (PMID = 17453377.001).
  • [ISSN] 0284-186X
  • [Journal-full-title] Acta oncologica (Stockholm, Sweden)
  • [ISO-abbreviation] Acta Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Antigens, CD
  • [Number-of-references] 17
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10. Jacobs SA, Foon KA: Monoclonal antibody therapy of leukaemias and lymphomas. Expert Opin Biol Ther; 2005 Sep;5(9):1225-43
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  • [Title] Monoclonal antibody therapy of leukaemias and lymphomas.
  • Rituximab, which is a chimeric monoclonal antibody produced by recombinant technology, became the first monoclonal antibody to be approved for haematological malignancies by the US Food and Drug Administration.
  • Radioimmunoconjugates are an attractive therapeutic option for lymphomas due to the inherent sensitivity to radiotherapy, the fact that the local emission of ionising radiation by radiolabelled antibodies may kill cells with or without the target antigen in close proximity to the bound antibody, and penetrating radiation may obviate the problem of limited antibody penetration into bulky, poorly vascularised tumours.
  • This paper reviews rituximab, alemtuzumab and gemtuzumab ozogamicin as monoclonal antibody therapies for leukaemias and lymphomas.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Leukemia / drug therapy. Lymphoma / drug therapy
  • [MeSH-minor] Animals. Antibodies, Monoclonal, Humanized. Antibodies, Monoclonal, Murine-Derived. Antigens, CD / immunology. Antigens, CD20 / immunology. Antigens, Differentiation, Myelomonocytic / immunology. Antigens, Neoplasm / immunology. Glycoproteins / immunology. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Myeloid, Acute / drug therapy. Leukemia, T-Cell / drug therapy. Lymphoma, B-Cell / drug therapy. Lymphoma, Follicular / drug therapy. Lymphoma, Mantle-Cell / drug therapy. Randomized Controlled Trials as Topic. Rituximab. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 16120052.001).
  • [ISSN] 1744-7682
  • [Journal-full-title] Expert opinion on biological therapy
  • [ISO-abbreviation] Expert Opin Biol Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antibodies, Neoplasm; 0 / Antigens, CD; 0 / Antigens, CD20; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antigens, Neoplasm; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / CD52 antigen; 0 / Glycoproteins; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab; 3A189DH42V / alemtuzumab; 4F4X42SYQ6 / Rituximab
  • [Number-of-references] 170
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11. Letestu R, Rawstron A, Ghia P, Villamor N, Boeckx N, Boettcher S, Buhl AM, Duerig J, Ibbotson R, Kroeber A, Langerak A, Le Garff-Tavernier M, Mockridge I, Morilla A, Padmore R, Rassenti L, Ritgen M, Shehata M, Smolewski P, Staib P, Ticchioni M, Walker C, Ajchenbaum-Cymbalista F: Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process. Cytometry B Clin Cytom; 2006 Jul 15;70(4):309-14
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process.
  • The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous with some patients requiring early therapy whereas others will not be treated for years.
  • The evaluation of an individual CLL patient's prognosis remains a problematic issue.
  • Among the available techniques for ZAP-70 detection, flow cytometry is most preferable as it allows the simultaneous quantification of ZAP-70 protein expression levels in CLL cells and residual normal lymphocyte subsets.
  • However, several factors introduce variability in the results reported from different laboratories; these factors include the anti-ZAP-70 antibody clone and conjugate, the staining procedure, the gating strategy, and the method of reporting the results.
  • During this workshop, a technical consensus was reached on the methods for cell permeabilization and immunophenotyping procedures.
  • This procedure was applied to three stabilized blood samples, provided by the UK NEQAS group to all participating members of this study, in order to minimize variability caused by sample storage and shipment.
  • Various gating strategies were used and the ZAP-70 levels were expressed as percentage positive (POS) relative to isotype control or normal B-cells or normal T-cells; in addition the levels were reported as a ratio of expression in CLL cells relative to T-cells.
  • The CLL/T-cell ZAP-70 expression ratio showed a much lower interlaboratory variation than other reporting strategies and is recommended for multicenter studies.
  • We assessed the variation of ZAP-70 expression levels in fresh cells according to storage time, which demonstrated that ZAP-70 is labile but sufficiently stable to allow comparison using fresh samples distributed between labs in Europe.
  • These studies have demonstrated progress toward a consensus reporting procedure, and further work is underway to harmonize the preparation and analysis procedures.
  • [MeSH-major] Flow Cytometry / methods. Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis. ZAP-70 Protein-Tyrosine Kinase / analysis
  • [MeSH-minor] Antibodies, Monoclonal / chemistry. Antibody Specificity. Anticoagulants / pharmacology. Antigen-Antibody Reactions. Biomarkers, Tumor / analysis. Biomarkers, Tumor / biosynthesis. Biomarkers, Tumor / immunology. Consensus. Humans. Immunoglobulin Heavy Chains / genetics. Immunoglobulin Variable Region / genetics. International Cooperation. Killer Cells, Natural / drug effects. Killer Cells, Natural / immunology. Mutation. Reproducibility of Results. T-Lymphocytes / drug effects. T-Lymphocytes / immunology

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  • [Copyright] (c) 2006 International Society for Analytical Cytology.
  • [ErratumIn] Cytometry B Clin Cytom. 2008 Jul;74(4):259. Leuven, Nancy Boeckx [corrected to Boeckx, Nancy]
  • (PMID = 16906588.001).
  • [ISSN] 1552-4949
  • [Journal-full-title] Cytometry. Part B, Clinical cytometry
  • [ISO-abbreviation] Cytometry B Clin Cytom
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Multicenter Study
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Anticoagulants; 0 / Biomarkers, Tumor; 0 / Immunoglobulin Heavy Chains; 0 / Immunoglobulin Variable Region; EC 2.7.10.2 / ZAP-70 Protein-Tyrosine Kinase; EC 2.7.10.2 / ZAP70 protein, human
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12. Wierda WG, Castro JE, Aguillon R, Sampath D, Jalayer A, McMannis J, Prussak CE, Keating M, Kipps TJ: A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154. Leukemia; 2010 Nov;24(11):1893-900
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154.
  • Ligation of CD40 on chronic lymphocytic leukemia (CLL) cells induces phenotypic and biochemical changes that facilitate CLL cell-T cell interactions and enhances the sensitivity of CLL cells to clearance by adaptive and innate immune-effector mechanisms.
  • CLL cells can be transduced to express CD40 ligand (CD154) using a replication-defective adenovirus vector, thereby cross-linking CD40 on transduced and non-transduced, bystander CLL cells.
  • In a previous study, patients received infusions of autologous CLL cells, transduced to express murine CD154 (mCD154), which induced anti-leukemic immune responses, but also anti-mCD154 antibodies.
  • In this study, we report a phase I study, in which patients were infused with 1 × 10(8), 3 × 10(8) or 1 × 10(9) autologous CLL cells transduced ex vivo to express ISF35, a humanized, membrane-stable CD154.
  • After infusion, circulating CLL cells had enhanced or de novo expression of CD95, DR5, p73 and Bid, which enhanced their susceptibility to death-receptor-mediated or drug-induced apoptosis, including CLL cells with deletions at 17p13.1 (del(17p)).
  • Two patients who had CLL with del(17p) had subsequent chemoimmunotherapy and responded well to treatment.
  • In summary, infusions of autologous, ISF35-transduced CLL cells were well tolerated, had biological and clinical activity, and might enhance the susceptibility of CLL cells with del(17p) to chemoimmunotherapy.
  • [MeSH-major] CD40 Ligand / therapeutic use. Genetic Therapy / methods. Leukemia, Lymphocytic, Chronic, B-Cell / therapy

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  • (PMID = 20882050.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P01 CA081534; United States / NCI NIH HHS / CA / P30 CA016672
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD40; 0 / Antigens, CD95; 147205-72-9 / CD40 Ligand
  • [Other-IDs] NLM/ NIHMS718310; NLM/ PMC4556366
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