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1. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia and natural killer cell leukemia/lymphomas. Curr Treat Options Oncol; 2003 Aug;4(4):289-96
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Large granular lymphocyte leukemia and natural killer cell leukemia/lymphomas.
  • Natural killer (NK) cell leukemia and lymphoma represent rare conditions with heterogeneity of biologic behavior, prognosis, and responsiveness to therapy.
  • The initial diagnosis of NK-cell malignancies can be difficult because of the lack of immunophenotypic clonality markers, morphologic heterogeneity, and a poor correlation between cytomorphology and prognosis.
  • Therapeutic recommendations for NK-cell malignancies are derived from retrospective studies or case reports.
  • Immature NK-cell malignancies often have aggressive behavior with poor prognosis, despite administration of acute myeloid leukemia or acute lymphocytic leukemia induction chemotherapy.
  • The use of high-dose chemotherapy with stem cell rescue resulted in a prolonged survival in a small series of patients.
  • NK-cell malignancies originating from cells with mature phenotypes form a spectrum of diseases with distinct prognosis.
  • Patients with aggressive NK-cell leukemia invariably die within several months.
  • Nasal and nasal-like NK/T-cell lymphomas with limited stage disease often respond to radiation therapy alone or combination with chemotherapy and radiation therapy, with 5-year disease-free survival rates ranging from 30% to 75%.
  • Patients with T-cell large granular lymphocyte leukemia or chronic NK-cell lymphoproliferative disease of granular lymphocytes can have an indolent clinical course with long survival without therapy.
  • However, approximately 66% of patients with T-cell large granular lymphocyte leukemia require low-dose chemotherapy with methotrexate or cyclophosphamide or immunosuppressive therapy with glucocorticosteroids or cyclosporine A for symptomatic cytopenias during the course of their disease.
  • [MeSH-major] Killer Cells, Natural. Leukemia / therapy. Lymphoma / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy


2. Burks EJ, Loughran TP Jr: Perspectives in the treatment of LGL leukemia. Leuk Res; 2005 Feb;29(2):123-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Perspectives in the treatment of LGL leukemia.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Leukemia, Lymphoid / drug therapy
  • [MeSH-minor] Clinical Trials as Topic / statistics & numerical data. Humans. Leukemia, T-Cell / classification. Leukemia, T-Cell / drug therapy. Leukemia, T-Cell / etiology. Leukocyte Count

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  • [CommentOn] Leuk Res. 2005 Feb;29(2):225-8 [15607372.001]
  • (PMID = 15607357.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Comment; Editorial; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 22
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3. Jaccard A, Petit B, Girault S, Suarez F, Gressin R, Zini JM, Coiteux V, Larroche C, Devidas A, Thiéblemont C, Gaulard P, Marin B, Gachard N, Bordessoule D, Hermine O: L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature. Ann Oncol; 2009 Jan;20(1):110-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature.
  • BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome.
  • PATIENTS AND METHODS: We report a multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers.
  • RESULTS: All but two of the patients had an objective response to L-asparaginase-based treatment.
  • CONCLUSION: These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia.
  • Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease.
  • First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.

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  • (PMID = 18701429.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Evaluation Studies; Journal Article; Multicenter Study; Review
  • [Publication-country] England
  • [Chemical-registry-number] EC 3.5.1.1 / Asparaginase
  • [Number-of-references] 26
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4. 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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5. Kelaidi C, Rollot F, Park S, Tulliez M, Christoforov B, Calmus Y, Podevin P, Bouscary D, Sogni P, Blanche P, Dreyfus F: Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas. Leukemia; 2004 Oct;18(10):1711-6
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  • [Title] Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas.
  • A link between chronic hepatitis C virus (HCV) infection and low-grade B-cell lymphomas has been suggested by epidemiological studies.
  • Marginal zone lymphomas (MZLs) including splenic lymphomas with villous lymphocytes are among the most frequently reported subgroups in the setting of chronic HCV infection.
  • In this study, we examined the effect of antiviral treatment in eight patients with HCV-associated MZL.
  • In addition, we report a case of large granular lymphocyte leukemia occurring in association with MZL and HCV, and responding to interferon and ribavirin.
  • We suggest that there is an etiologic link between HCV and antigen-driven lymphoproliferative disorders.
  • [MeSH-major] Antiviral Agents / therapeutic use. Hepacivirus / pathogenicity. Hepatitis C / drug therapy. Lymphoma, B-Cell / virology
  • [MeSH-minor] Adult. Aged. Drug Therapy, Combination. Female. Humans. Interferon-alpha / therapeutic use. Male. Middle Aged. Prospective Studies. Retrospective Studies. Ribavirin / therapeutic use. Treatment Outcome

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  • [CommentIn] Leukemia. 2004 Oct;18(10):1572-5 [15284857.001]
  • (PMID = 15284859.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Interferon-alpha; 49717AWG6K / Ribavirin
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6. Hoshino T, Tahara K, Miyawaki K, Hatsumi N, Takada S, Miyawaki S, Sakura T: [Clinical profiles of 7 patients with chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib]. Rinsho Ketsueki; 2010 Mar;51(3):181-8
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  • [Title] [Clinical profiles of 7 patients with chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib].
  • We retrospectively analyzed the clinical outcome of dasatinib in 7 patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant or intolerant to imatinib.
  • Three patients with chronic phase CML and two patients with Ph+ALL achieved major molecular response, however, two CML patients in accelerated phase (AP)/blast crisis (BC), did not.
  • No patients who had been intolerant to imatinib experienced the same nonhematologic toxicity following treatment with dasatinib.
  • We identified three patients who developed peripheral lymphocytosis, identified as natural killer cells or cytotoxic T-cells based on their large granular lymphocyte (LGL) morphologies and immunophenotypic profiles, out of six patients receiving dasatinib therapy.
  • All three cases that developed LGL lymphocytosis achieved optimal molecular response, two of the patients, however, had pleural effusion and CMV colitis, respectively.
  • Dasatinib inhibits off-target kinases, which may result in unexpected drug responses.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Pyrimidines / administration & dosage. Thiazoles / administration & dosage
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Colitis / chemically induced. Colitis / virology. Cytomegalovirus Infections. Dasatinib. Humans. Middle Aged. Pleural Effusion / chemically induced. Retrospective Studies. Treatment Outcome


7. Alekshun TJ, Sokol L: Diseases of large granular lymphocytes. Cancer Control; 2007 Apr;14(2):141-50
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  • [Title] Diseases of large granular lymphocytes.
  • BACKGROUND: Clonal diseases of large granular lymphocytes (LGLs) are rare lymphoproliferative malignancies that arise from either mature T-cell (CD3+) or natural killer (NK)-cell (CD3-) lineages.
  • They manifest a distinct biologic behavior that ranges from indolent to very aggressive.
  • METHODS: We discuss four distinct diseases involving LGLs: indolent T-cell LGL leukemia, aggressive T-cell LGL leukemia, chronic NK-cell leukemia, and aggressive NK-cell leukemia.
  • Furthermore, we present an up-to-date systematic review of therapies for each entity.
  • RESULTS: Sustained LGLs, characteristic immunophenotype, clonal origin of leukemic cells, and clinical presentation are the most important features that distinguish indolent from aggressive subtypes of LGL leukemia and guide the selection of therapy.
  • Patients with symptomatic indolent T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies in contrast to aggressive T-cell and NK-cell LGL leukemia, which require intensive chemotherapy induction regimens.
  • Novel targeted therapies using monoclonal antibodies against receptors, including CD2, CD52, the beta subunit of the interleukin-2 receptor, and small molecules such as tipifarnib, are undergoing evaluation in clinical trials.
  • CONCLUSIONS: Future scientific advances focusing on the delineation of molecular pathogenic mechanisms and the development of new targeted therapies for each distinct LGL leukemia entity should lead to improved outcomes of patients with these disorders.
  • [MeSH-major] Antigens, CD3. Killer Cells, Natural / pathology. Leukemia, Lymphoid / pathology. Leukemia, T-Cell / pathology. Lymphocytes / pathology

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  • (PMID = 17387299.001).
  • [ISSN] 1073-2748
  • [Journal-full-title] Cancer control : journal of the Moffitt Cancer Center
  • [ISO-abbreviation] Cancer Control
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD3
  • [Number-of-references] 71
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8. Au WY, Lam CC, Chim CS, Pang AW, Kwong YL: Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia. Leuk Res; 2005 Oct;29(10):1213-5
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  • [Title] Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia.
  • Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone, dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52 antibody).
  • Case 2, a 42-year-old man with PRCA due to T-cell large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only transiently.
  • Alemtuzumab is active in PRCA that is idiopathic or secondary to T-cell lymphoproliferative diseases.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Drug Resistance, Neoplasm. Leukemia, T-Cell / drug therapy. Red-Cell Aplasia, Pure / drug therapy

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  • (PMID = 16111536.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antilymphocyte Serum; 0 / Antineoplastic Agents; 3A189DH42V / alemtuzumab; 7S5I7G3JQL / Dexamethasone; 83HN0GTJ6D / Cyclosporine; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; BZ114NVM5P / Mitoxantrone; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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9. Lamy T, Loughran TP Jr: Clinical features of large granular lymphocyte leukemia. Semin Hematol; 2003 Jul;40(3):185-95
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Clinical features of large granular lymphocyte leukemia.
  • The spectrum of large granular lymphocyte (LGL) proliferations consists of four distinct entities: reactive/transient LGL expansion, chronic LGL lymphocytosis, classical indolent LGL leukemia, and aggressive LGL leukemia.
  • LGL leukemias are classified as lymphoid malignancies.
  • They are divided into CD3(+)/T-cell LGL (85% of cases) and CD3(-)/natural killer (NK) cell LGL leukemia (15% of cases).
  • Identification of LGL expansion has been improved using T-cell receptor (TCR)beta/gamma polymerase chain reaction (PCR) analysis and a combination of Vbeta and killer cell immunoglobulin-like receptor (KIR)-specific monoclonal antibodies.
  • LGL leukemias are characterized by a clonal LGL infiltration of the bone marrow, spleen, and liver.
  • T-LGL leukemias affect the elderly and display a relatively indolent behavior.
  • Approximately 60% to 70% of patients are symptomatic: recurrent infections secondary to chronic neutropenia, anemia, and autoimmune disease such as rheumatoid arthritis are the main clinical manifestations.
  • Conversely, NK LGL leukemias behave aggressively, and most patients do not respond to chemotherapy.
  • [MeSH-major] Leukemia, Lymphoid / pathology
  • [MeSH-minor] Autoimmune Diseases. Clone Cells / immunology. Clone Cells / pathology. Hematologic Diseases. Humans. Killer Cells, Natural / immunology. Killer Cells, Natural / pathology. T-Lymphocytes / immunology. T-Lymphocytes / pathology


10. Ishida F, Kwong YL: Diagnosis and management of natural killer-cell malignancies. Expert Rev Hematol; 2010 Oct;3(5):593-602
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  • [Title] Diagnosis and management of natural killer-cell malignancies.
  • Natural killer (NK)-cell malignancies are uncommon neoplasms, which have been referred to as polymorphic reticulosis or angiocentric T-cell lymphomas in the past.
  • In the current WHO classification, they are categorized as extranodal NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia.
  • NK-cell malignancies show a geographical predilection for Asian and South American populations and are rare in the west.
  • Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with angioinvasion and angiodestruction.
  • The lymphoma cells are CD2(+), cytoplasmic CD3ε(+) and CD56(+), with germline T-cell receptor gene.
  • Clinically, NK-cell lymphomas can be classified into nasal, non-nasal and aggressive lymphoma/leukemia subtypes.
  • Most nasal NK-cell lymphomas present with stage I/II disease.
  • The early use of radiotherapy, either alone or concomitantly/sequentially with chemotherapy, is the most important factor in achieving successful treatment.
  • Many stage I/II patients receiving radiotherapy alone fail systemically, so the use of chemotherapy is also considered necessary.
  • Chemotherapy is indicated for stage III/IV nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes.
  • Recent regimens that incorporate the use of L-asparaginase have resulted in substantial improvements in outcome in high-risk, refractory or relapsed patients.
  • High-dose chemotherapy and hematopoietic stem-cell transplantation with autologous or allogeneic hematopoietic stem cells may be beneficial to selected patients.
  • Prognostication of patients with clinical prognostic models and presentation circulating Epstein-Barr DNA load may be useful in the stratification of patients for various treatment modalities.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Asparaginase / administration & dosage. Killer Cells, Natural / drug effects. Leukemia / diagnosis. Leukemia / therapy. Lymphoma, Extranodal NK-T-Cell / diagnosis. Lymphoma, Extranodal NK-T-Cell / therapy
  • [MeSH-minor] Antigens, CD. Asia / epidemiology. Female. Hematopoietic Stem Cell Transplantation. Herpesvirus 4, Human. Humans. Male. Middle Aged. Prognosis. Recurrence. Severity of Illness Index. South America / epidemiology. Transplantation, Autologous

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  • (PMID = 21083476.001).
  • [ISSN] 1747-4094
  • [Journal-full-title] Expert review of hematology
  • [ISO-abbreviation] Expert Rev Hematol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD; EC 3.5.1.1 / Asparaginase
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11. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Oncologist; 2006 Mar;11(3):263-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Large granular lymphocyte leukemia.
  • Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3-).
  • Both subtypes, T-cell and NK-cell LGL leukemia, can manifest as indolent or aggressive disorders.
  • The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years.
  • Immunosuppressive therapy with low-dose methotrexate, cyclophosphamide, or cyclosporine A can control symptoms and cytopenias in more than 50% of patients, but this approach is not curative.
  • Several cases of an aggressive variant (CD3+ CD56+) of T-cell LGL leukemia with a poor prognosis have also been reported.
  • Aggressive NK-cell LGL leukemia is usually a rapidly progressive disorder associated with Epstein-Barr virus (EBV), with a higher prevalence in Asia and South America.
  • This disease is usually refractory to conventional chemotherapy, with a median survival time of 2 months.
  • Chronic NK-cell leukemia/lymphocytosis is a rare EBV-negative disorder with an indolent clinical course.
  • The malignant origin of this subtype is uncertain because clonality is difficult to determine in LGLs of NK-cell origin.
  • [MeSH-major] Leukemia, T-Cell / diagnosis. Leukemia, T-Cell / therapy
  • [MeSH-minor] Algorithms. Autoimmune Diseases / etiology. Cytogenetic Analysis. Diagnosis, Differential. Hematologic Diseases / etiology. Humans. Phenotype

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  • (PMID = 16549811.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 76
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12. Vigouroux S, Michallet M, Porcher R, Attal M, Ades L, Bernard M, Blaise D, Tabrizi R, Garban F, Cassuto JP, Chevalier P, Facon T, Ifrah N, Renaud M, Tilly H, Vernant JP, Kuentz M, Bourhis JH, Bordigoni P, Deconinck E, Lioure B, Socié G, Milpied N, French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC): Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC). Haematologica; 2007 May;92(5):627-34
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  • [Title] Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC).
  • BACKGROUND AND OBJECTIVES: High-dose chemotherapy with allogeneic stem cell transplantation (SCT) has proven to be a successful treatment for low-grade lymphoma (LGL), but is associated with considerable transplant-related mortality (TRM).
  • In an effort to reduce toxic mortality while maintaining the graft-versus-leukemia effect, allogeneic SCT has been combined with a reduced-intensity conditioning (RIC) regimen.
  • The aim of this study was to determine the outcome of patients with LGL treated with RIC allogeneic SCT.
  • DESIGN AND METHODS: This retrospective multicenter study included 73 patients with relapsed or refractory LGL allografted after a RIC regimen between 1998 and 2005 whose data were recorded in a French registry.
  • RESULTS: Patients received a median of three lines of therapy prior to RIC allogeneic SCT.
  • Prior to allografting, patients were in complete response (CR; n=21), partial response (PR; n=33) or had chemoresistant disease (n=19).
  • In patients in CR, PR and chemoresistant disease, the 3-year overall survival rates were 66%, 64% and 32%, respectively, while the 3-year event-free survival rates were 66%, 52% and 32%, respectively.
  • INTERPRETATION AND CONCLUSIONS: Although associated with significant TRM, RIC allogeneic SCT in advanced chemosensitive disease leads to long-term survival.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / statistics & numerical data. Lymphoma, Non-Hodgkin / surgery. Transplantation Conditioning / methods
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal / therapeutic use. Antilymphocyte Serum / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Busulfan / administration & dosage. Carmustine / administration & dosage. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Data Collection. Disease-Free Survival. Etoposide / administration & dosage. Female. France. Graft vs Host Disease / epidemiology. Graft vs Host Disease / etiology. Graft vs Leukemia Effect. Humans. Kaplan-Meier Estimate. Male. Melphalan / administration & dosage. Middle Aged. Proportional Hazards Models. Remission Induction. Retrospective Studies. Salvage Therapy. Survival Analysis. Survival Rate. T-Lymphocytes. Transplantation, Homologous. Treatment Outcome. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives. Whole-Body Irradiation

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  • [CommentIn] Haematologica. 2007 May;92(5):580-2 [17488679.001]
  • (PMID = 17488686.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antilymphocyte Serum; 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine; Q41OR9510P / Melphalan; U68WG3173Y / Carmustine; BEAM regimen
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13. Greer JP, Kinney MC, Loughran TP Jr: T cell and NK cell lymphoproliferative disorders. Hematology Am Soc Hematol Educ Program; 2001;:259-81
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] T cell and NK cell lymphoproliferative disorders.
  • This review covers the diagnosis and management of natural killer and peripheral T-cell lymphomas (PTCL).
  • Kinney gives a general overview of the diagnosis of PTCL and NK cell neoplasms.
  • Emphasis will be placed on extranodal T cell and natural killer (NK) cell lymphomas such as hepatosplenic lymphoma, subcutaneous panniculitis-like lymphoma and nasal/nasal type T/NK-cell lymphoma.
  • The use of ALK gene regulation in the classification of anaplastic large cell lymphoma is also reviewed. Dr.
  • Loughran describes current understanding of the pathogenesis of large granular lymphocyte (LGL) leukemia.
  • The discussion focuses on LGL leukemia as an instructive model of dysregulated apoptosis causing both malignant and autoimmune disease.
  • Current management options and mechanisms of therapeutic response are also described. Dr.
  • Greer addresses whether PTCL should be treated differently from the more common diffuse large B cell lymphomas.
  • He discusses the therapeutic options for anaplastic large cell lymphoma (ALCL), from a conservative approach for primary cutaneous ALCL to combination chemotherapy for the highly chemosensitive ALCL expressing anaplastic lymphoma kinase.
  • He reviews therapy options for the extranodal subtypes of PTCL by drawing from series in adults, pediatrics, dermatology, and the Far East.

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  • (PMID = 11722988.001).
  • [ISSN] 1520-4391
  • [Journal-full-title] Hematology. American Society of Hematology. Education Program
  • [ISO-abbreviation] Hematology Am Soc Hematol Educ Program
  • [Language] ENG
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 241
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14. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Curr Hematol Malig Rep; 2007 Oct;2(4):278-82
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  • [Title] Large granular lymphocyte leukemia.
  • Clonal diseases of large granular lymphocytes (LGLs) represent a spectrum of clinically rare lymphoproliferative malignancies arising from either mature T-cell (CD3(+)) or natural killer (NK)-cell (CD3(-)) lineages.
  • The clinical behavior of these disorders ranges from indolent to very aggressive.
  • Patients with symptomatic indolent T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies; in contrast, aggressive T-cell or NK-cell LGL leukemias require intensive chemotherapy regimens.
  • Novel targeted therapies are currently being tested in clinical studies.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic
  • [MeSH-minor] Adolescent. Adult. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Clinical Trials as Topic. Combined Modality Therapy. Disease Progression. Female. Humans. Immunophenotyping. Killer Cells, Natural / pathology. Leukemia, T-Cell / complications. Leukemia, T-Cell / epidemiology. Leukemia, T-Cell / immunology. Leukemia, T-Cell / pathology. Leukemia, T-Cell / therapy. Male. Middle Aged. Myelodysplastic Syndromes / pathology. Neutropenia / etiology. Opportunistic Infections / etiology. Stem Cell Transplantation

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  • (PMID = 20425381.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 3A189DH42V / alemtuzumab
  • [Number-of-references] 39
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15. Tse E, Liang RH: Natural killer cell neoplasms. Clin Lymphoma; 2004 Dec;5(3):197-201
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Natural killer cell neoplasms.
  • Lymphoid neoplasms that are derived from natural killer (NK) cells are uncommon but distinct clinicopathologic disease entities.
  • Three types have been recognized and categorized in the latest World Health Organization classification: extranodal NK cell lymphoma, nasal-type; aggressive NK cell leukemia; and blastic NK cell lymphoma.
  • All NK tumor cells express the NK cell marker CD56, but they lack the expression of surface CD3 and the rearrangement of T-cell receptor genes, which distinguish them from T-lymphoid neoplasms.
  • There is also a strong association with the Epstein-Barr virus, except in blastic NK cell lymphoma.
  • Extranodal involvement by the NK cell tumor is common, especially in the nasal cavity, the skin, and the gastrointestinal tract.
  • All 3 NK cell neoplasms are characterized by aggressive clinical course and poor response to treatment.
  • Although the optimal treatment modality remains to be determined, good initial response to combined radiation therapy and chemotherapy has been observed in localized disease.
  • Further studies in the basic biology of the NK cell and the pathology of NK cell neoplasms may shed light on the development of newer and more effective therapy.
  • [MeSH-major] Killer Cells, Natural / pathology. Lymphoma / immunology. Lymphoma / pathology
  • [MeSH-minor] Adult. B-Lymphocytes / immunology. Female. Humans. Male. Skin Neoplasms / immunology. Skin Neoplasms / pathology. T-Lymphocytes / immunology

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  • (PMID = 15636697.001).
  • [ISSN] 1526-9655
  • [Journal-full-title] Clinical lymphoma
  • [ISO-abbreviation] Clin Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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16. Sretenovic A, Antic D, Jankovic S, Gotic M, Perunicic-Jovanovic M, Jakovic L, Mihaljevic B: T-cell large granular lymphocytic (T-LGL) leukemia: a single institution experience. Med Oncol; 2010 Jun;27(2):286-90
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  • [Title] T-cell large granular lymphocytic (T-LGL) leukemia: a single institution experience.
  • BACKGROUND: T-cell large granular lymphocytic (T-LGL) leukemia is a rare lymphoproliferative disease which usually affects elderly people.
  • The clinical course of T-LGL leukemia is generally indolent, with lymphocytosis and splenomegaly in 20-50% patients, hepatomegaly in 5-20% of patients, and less commonly, lymphadenopathy.
  • T-LGL leukemia is associated with immunological abnormalities: rheumatoid factor with or without rheumatoid arthritis (RA), Coombs positive hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), positive anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), hypogammaglobulinemia, and polyclonal hypergammaglobulinemia.
  • Aim To compare clinical and laboratory features of T-LGL leukemia patients and their responses to different chemotherapy regimens.
  • METHODS: Six patients (3 males and 3 females) with T-LGL leukemia were analyzed.
  • The diagnosis was based on accepted morphologic criteria, immunophenotype, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangements.
  • RESULTS: All patients exhibited lymphocytosis, mainly with unusual morphologies, splenomegaly, and elevated serum lactate dehydrogenase (LDH).
  • Three patients were treated with a Fludarabine-Cyclophosphamide (FC) combination as initial therapy while three patients received CHOP.
  • Two patients received more than one treatment regimen.
  • One patient died due to T-LGL leukemia in first year after diagnosis, one patient died 4 years after diagnosis, two patients interrupted their treatment, and two patients are still alive.
  • CONCLUSIONS: Further prospective studies are needed for establishing a gold standard therapy for T-LGL leukemia.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / blood. Leukemia, Large Granular Lymphocytic / drug therapy
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cyclophosphamide / therapeutic use. Doxorubicin / therapeutic use. Female. Follow-Up Studies. Humans. Male. Middle Aged. Prednisone / therapeutic use. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use. Vincristine / therapeutic use

  • Hazardous Substances Data Bank. FLUDARABINE .
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  • NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .
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  • (PMID = 19306076.001).
  • [ISSN] 1559-131X
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; VB0R961HZT / Prednisone; CHOP protocol
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17. Kreutzman A, Juvonen V, Kairisto V, Ekblom M, Stenke L, Seggewiss R, Porkka K, Mustjoki S: Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood; 2010 Aug 5;116(5):772-82
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  • [Title] Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy.
  • In a proportion of patients with chronic myeloid leukemia (CML) being treated with dasatinib, we recently observed large granular lymphocyte (LGL) expansions carrying clonal T-cell receptor (TCR) gamma/delta gene rearrangements.
  • To assess the prevalence and role of clonal lymphocytes in CML, we collected samples from patients (n = 34) at the time of diagnosis and during imatinib and dasatinib therapies and analyzed lymphocyte clonality with a sensitive polymerase chain reaction-based method of TCR gamma and delta genes.
  • Surprisingly, at CML diagnosis, 15 of 18 patients (83%) had a sizeable clonal, BCR-ABL1 negative lymphocyte population, which was uncommon in healthy persons (1 of 12; 8%).
  • In contrast, in a distinct population of dasatinib-treated patients, the diagnostic phase clone markedly expanded, resulting in absolute lymphocytosis in blood.
  • Most patients with LGL expansions (90%) had TCR delta rearrangements, which were uncommon in patients without an LGL expansion (10%).
  • The TCR delta clones were confined to gammadelta(+) T- or natural killer-cell compartments and the TCR gamma clones to CD4(+)/CD8(+) alphabeta(+) fractions.
  • The functional importance of clonal lymphocytes as a part of leukemia immune surveillance and the putative anergy-reversing role of dasatinib require further evaluation.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Clone Cells / pathology. Killer Cells, Natural / pathology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology. Protein Kinase Inhibitors / therapeutic use. Pyrimidines / therapeutic use. T-Lymphocyte Subsets / pathology. Thiazoles / therapeutic use
  • [MeSH-minor] Adult. Aged. Benzamides. CD8-Positive T-Lymphocytes / chemistry. CD8-Positive T-Lymphocytes / pathology. Clonal Anergy. Cytomegalovirus / physiology. Dasatinib. Female. Fusion Proteins, bcr-abl / analysis. Fusion Proteins, bcr-abl / antagonists & inhibitors. Gene Rearrangement, delta-Chain T-Cell Antigen Receptor. Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor. Humans. Imatinib Mesylate. Immunologic Surveillance. Lymphocyte Count. Male. Middle Aged. Piperazines / therapeutic use. Receptors, Antigen, T-Cell, gamma-delta / genetics. Virus Activation / drug effects. Young Adult


18. Fortune AF, Kelly K, Sargent J, O'Brien D, Quinn F, Chadwick N, Flynn C, Conneally E, Browne P, Crotty GM, Thornton P, Vandenberghe E: Large granular lymphocyte leukemia: natural history and response to treatment. Leuk Lymphoma; 2010 May;51(5):839-45
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  • [Title] Large granular lymphocyte leukemia: natural history and response to treatment.
  • Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available.
  • We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm.
  • The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5).
  • Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective.
  • Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity.
  • The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively.
  • Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cyclosporine / therapeutic use. Immunosuppressive Agents / therapeutic use. Leukemia, Large Granular Lymphocytic / drug therapy
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / administration & dosage. Drug Therapy, Combination. Female. Humans. Male. Methotrexate / administration & dosage. Middle Aged. Pentostatin / administration & dosage. Survival Rate. Treatment Outcome

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  • (PMID = 20367569.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Immunosuppressive Agents; 395575MZO7 / Pentostatin; 3A189DH42V / alemtuzumab; 83HN0GTJ6D / Cyclosporine; YL5FZ2Y5U1 / Methotrexate
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19. Saitoh T, Karasawa M, Sakuraya M, Norio N, Junko T, Shirakawa K, Matsushima T, Tsukamoto N, Nojima Y, Murakami H: Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity. Eur J Haematol; 2000 Oct;65(4):272-5
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  • [Title] Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity.
  • We report a case of gammadelta T-cell-type large granular lymphocyte (LGL) leukemia (CD3 +,CD8 +, CD57 +,TCR gammadelta+), which was accompanied by pure red cell aplasia, neutropenia and thrombocytosis.
  • Southern blotting analysis of the T-cell receptor beta gene showed the germline configuration, but clonal TCR J gamma rearrangements were identified.
  • These granular lymphocytes demonstrated non-major histocompatibility complex-restricted cytotoxicitity.
  • After treatment with cyclosporin A, anemia and thrombocytosis were improved, and LGL and the elevated sFasL concentration decreased.
  • These observations suggested that FasL may have played a role in the establishment of the clinical symptoms of this patient and could be useful as an indicator of disease activity.
  • [MeSH-major] Cyclosporine / administration & dosage. Leukemia, Lymphoid / drug therapy. Leukemia, T-Cell / drug therapy
  • [MeSH-minor] Antigens, CD3 / blood. Antigens, CD95 / blood. Humans. Immunophenotyping. Male. Middle Aged. Receptors, Antigen, T-Cell, gamma-delta / blood. Red-Cell Aplasia, Pure / drug therapy. Red-Cell Aplasia, Pure / etiology. Thrombocytosis / drug therapy. Thrombocytosis / etiology. Treatment Outcome


20. Greer JP, Mosse CA: Natural killer-cell neoplasms. Curr Hematol Malig Rep; 2009 Oct;4(4):245-52
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  • [Title] Natural killer-cell neoplasms.
  • The natural killer (NK)-cell neoplasms are rare, representing less than 1% of non-Hodgkin lymphoma, except in Asia and Latin America, where they represent 3% to 6%.
  • NK-cell neoplasms include immature acute leukemias; a blastic NK-cell lymphoma, which is obsolete because of its plasmacytoid dendritic-cell origin; and mature NK neoplasms, comprising extranodal NK/T-cell lymphoma (ENKL), nasal-type; aggressive NK-cell leukemia; and chronic NK-cell lymphoproliferative disorders, which are often reactive.
  • Epstein-Barr virus is usually detected in tumor cells of ENKL and aggressive NK-cell leukemia.
  • The latter two mature NK neoplasms are relatively chemoresistant because of the frequent expression of P-glycoprotein.
  • Stem cell transplantation is recommended for advanced disease, owing to a poor prognosis.
  • Novel agents, including chemotherapy, inhibitors of molecular pathways, and monoclonal antibodies, are under investigation.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Lymphoma / pathology. Lymphoproliferative Disorders / pathology
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Cell Lineage. Cell Transformation, Neoplastic. Humans. Stem Cell Transplantation

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  • (PMID = 20425414.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 42
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21. Krick EL, Little L, Patel R, Shofer FS, Sorenmo K, Clifford CA, Baez JL: Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004). Vet Comp Oncol; 2008 Jun;6(2):102-10
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  • [Title] Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004).
  • Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma.
  • Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times.
  • The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma.
  • Medical records of 45 cats with LGL lymphoma were retrospectively evaluated.
  • All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative.
  • One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment.
  • Median survival time for cats that were treated was 57 days.
  • Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Cat Diseases / pathology. Lymphoma / veterinary. Precursor Cell Lymphoblastic Leukemia-Lymphoma / veterinary
  • [MeSH-minor] Animals. Cats. Female. Immunohistochemistry / veterinary. Male. Prognosis. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 19178669.001).
  • [ISSN] 1476-5829
  • [Journal-full-title] Veterinary and comparative oncology
  • [ISO-abbreviation] Vet Comp Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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22. Christopoulos PD, Katsoudas S, Androulaki A, Nakopoulou L, Economopoulos T, Vlahakos DV: T-cell large granular lymphocyte leukemia presenting as end-stage renal disease: the diagnostic role of flow-cytometric and clonality analysis of the urine sediment. Clin Nephrol; 2009 Feb;71(2):198-202
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  • [Title] T-cell large granular lymphocyte leukemia presenting as end-stage renal disease: the diagnostic role of flow-cytometric and clonality analysis of the urine sediment.
  • Several liver and bone marrow biopsies during that period had shown a nonspecific polyclonal T-cell infiltration, and she was administered low-dose steroids for symptomatic relief.
  • Physical examination, laboratory workup and imaging studies at presentation showed pancytopenia, hepatosplenomegaly, large symmetric kidneys with normal cortices and no evidence of obstructive uropathy, aseptic pyuria with neutrophils and lymphocytes and mild proteinuria.
  • On biopsy the renal interstitium was infiltrated by large, granular CD3+CD8+CD56-CD57+ lymphocytes, clonal by molecular analysis, which established the diagnosis of T-cell large granular lymphocyte leukemia.
  • Most urinary and peripheral blood lymphocytes bore the same T-LGL surface markers and were also clonal, as shown by flow-cytometry and PCR amplification of the T-cell receptor g-chain genes.
  • After exclusion of an underlying EBV, CMV, HBV, HCV or HIV infection with negative serology and blood PCR the patient received one cycle of chemotherapy with cyclophosphamide, vincristine and prednisone.
  • No improvement of renal function was achieved, while complication with a prolonged pulmonary infection and severe sepsis precluded further treatment.
  • Our report indicates that the T-LGL leukemia should be considered in the differential diagnosis of renal failure with large-sized kidneys, especially when hepatosplenomegaly, pancytopenia and aseptic pyuria are also present.
  • In the latter case, flow-cytometric and clonality analysis of the urine sediment can aid in establishing a diagnosis.
  • Since renal function may deteriorate rapidly, chemotherapy should not be delayed.
  • [MeSH-major] Flow Cytometry. Kidney Failure, Chronic / diagnosis. Leukemia, Large Granular Lymphocytic / diagnosis
  • [MeSH-minor] Aged. Diagnosis, Differential. Female. Humans. Tomography, X-Ray Computed


23. Osuji N, Matutes E, Tjonnfjord G, Grech H, Del Giudice I, Wotherspoon A, Swansbury JG, Catovsky D: T-cell large granular lymphocyte leukemia: A report on the treatment of 29 patients and a review of the literature. Cancer; 2006 Aug 1;107(3):570-8
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  • [Title] T-cell large granular lymphocyte leukemia: A report on the treatment of 29 patients and a review of the literature.
  • BACKGROUND: To the authors' knowledge, there is no standard treatment for patients with T-cell large granular lymphocyte (LGL) leukemia.
  • METHODS: The authors report on the use of immunosuppressants (cyclosporin A [CSA] and low-dose oral methotrexate [MTX] given continuously) and cytotoxic agents in the treatment of 29 patients with T-cell LGL leukemia age over the past 20 years.
  • The median time to response for both agents was 1 month.
  • An ORR of 67% (all CHR) was attained with pentostatin (n = 4 patients); recurrences developed after a median of 4.6 years.
  • Successful retreatment with pentostatin was possible but with increasing drug resistance.
  • Alemtuzumab induced a PR in 1 patient who had refractory disease.
  • CONCLUSIONS: Both MTX and CSA were efficacious in the treatment of T-cell LGL leukemia but generally required long-term maintenance therapy.
  • The authors highlight the risks of second malignancies and persistence of bone marrow disease.
  • Although MTX and CSA were effective as first-line therapy, alemtuzumab and pentostatin merit further investigation, particularly for refractory disease.
  • [MeSH-major] Immunosuppressive Agents / therapeutic use. Leukemia, Lymphoid / drug therapy. Leukemia, T-Cell / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Cyclophosphamide / therapeutic use. Cyclosporine / therapeutic use. Databases as Topic. Female. Humans. Male. Methotrexate / therapeutic use. Middle Aged. Pentostatin / therapeutic use. Retrospective Studies


24. Starkebaum G: Chronic neutropenia associated with autoimmune disease. Semin Hematol; 2002 Apr;39(2):121-7
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  • [Title] Chronic neutropenia associated with autoimmune disease.
  • Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE).
  • Recent advances have allowed better understanding regarding the mechanism of neutropenia and improved options for treatment.
  • The role of soluble Fas-ligand (FasL) in inducing apoptosis of neutrophils has been clarified for LGL leukemia and increased neutrophil apoptosis has been described in neutropenic patients with SLE.
  • Treatments of neutropenia have included methotrexate, cyclosporine A, and granulocyte colony-stimulating factor (G-CSF) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF).
  • [MeSH-minor] Antibodies, Antineutrophil Cytoplasmic / immunology. Chronic Disease. Humans. Neutropenia / drug therapy. Neutropenia / etiology. Neutropenia / immunology. Neutrophils / drug effects. Neutrophils / immunology. Neutrophils / pathology

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  • (PMID = 11957195.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Antineutrophil Cytoplasmic
  • [Number-of-references] 58
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25. Epling-Burnette PK, Sokol L, Chen X, Bai F, Zhou J, Blaskovich MA, Zou J, Painter JS, Edwards TD, Moscinski L, Yoder JA, Djeu JY, Sebti S, Loughran TP Jr, Wei S: Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling. Blood; 2008 Dec 1;112(12):4694-8
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  • [Title] Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling.
  • Large granular lymphocyte (LGL) leukemia is commonly associated with poor hematopoiesis.
  • The first case of pulmonary artery hypertension (PAH) was observed in a 57-year-old woman with natural killer (NK)-LGL leukemia and transfusion-dependent anemia.
  • Using a genetic approach, we demonstrated that killing of pulmonary endothelial cells by patient NK cells was mediated by dysregulated balance in activating and inhibitory NK-receptor signaling.
  • Elevated pulmonary artery pressure and erythroid differentiation improved after disrupting the NK-receptor signaling pathway with 4 courses of a farnesyltransferase inhibitor, tipifarnib.
  • Coincidental association between PAH and LGL leukemia suggest a causal relationship between the expanded lymphocyte population and these clinical manifestations.

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  • (PMID = 18791165.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA098472; United States / NCRR NIH HHS / RR / U54 RR019397; United States / NIAID NIH HHS / AI / AI056213; United States / NCI NIH HHS / CA / CA94872; United States / NCRR NIH HHS / RR / U54RR019397-05; United States / NCI NIH HHS / CA / CA11211201; United States / NIAID NIH HHS / AI / R01 AI056213
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; 0 / Quinolones; 0 / Receptors, Natural Killer Cell; 192185-72-1 / tipifarnib; EC 2.5.1.29 / Farnesyltranstransferase
  • [Other-IDs] NLM/ PMC2597136
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26. Takahashi T, Otani I, Okuda M, Inoue M, Ito K, Sakai M, Koie H, Yamaya Y, Watari T, Sato T, Kanayama K, Tokuriki M: Malignant transformation of T-cell large granular lymphocyte leukemia in a dog. J Vet Med Sci; 2007 Jun;69(6):677-81
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  • [Title] Malignant transformation of T-cell large granular lymphocyte leukemia in a dog.
  • An 8-year-old spayed female Golden Retriever was referred to us for evaluation of mild lymphocytosis.
  • The peripheral lymphocytes were comprised of mostly large granular lymphocytes (LGLs), and flow cytometry showed that they were mostly CD3+8+ T lymphocytes.
  • Clonal rearrangement of the T-cell receptor gene was identified in the peripheral blood, and the dog was therefore diagnosed with LGL chronic leukemia.
  • The dog was subclinical without treatment until hospitalization on day 154, at which point the lymphocytes looked like lymphoblasts and the surface markers changed to CD3-8-.
  • This was regarded as malignant transformation from LGL chronic leukemia to the acute type.
  • Sequential chemotherapy was started, but the dog died on day 190.
  • Necropsy revealed tumor cell infiltration into the heart, skin, and brain.

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  • (PMID = 17611371.001).
  • [ISSN] 0916-7250
  • [Journal-full-title] The Journal of veterinary medical science
  • [ISO-abbreviation] J. Vet. Med. Sci.
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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27. Cheung MM, Chan JK, Wong KF: Natural killer cell neoplasms: a distinctive group of highly aggressive lymphomas/leukemias. Semin Hematol; 2003 Jul;40(3):221-32
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  • [Title] Natural killer cell neoplasms: a distinctive group of highly aggressive lymphomas/leukemias.
  • Natural killer (NK) cell neoplasms, which include extranodal NK/T-cell lymphoma (nasal and extranasal) and aggressive NK cell leukemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent.
  • These neoplasms are highly aggressive, and show a strong association with Epstein-Barr virus.
  • Extranodal NK/T-cell lymphoma most commonly affects the nasal cavity and other mucosal sites of the upper aerodigestive tract.
  • Despite the early stage of disease at presentation, overall survival is poor.
  • Patients with the extranasal form of the lymphoma often present with high-stage disease, commonly involving the skin, gastrointestinal tract, testis, and soft tissue, and the prognosis is even worse.
  • Based on currently available data, treatment of nasal NK/T-cell lymphoma should consist of radiotherapy, with or without multiagent chemotherapy.
  • More research is required to ascertain the role of high-dose chemotherapy with stem cell rescue and that of non-multidrug resistance-related chemotherapeutic agents.
  • Aggressive NK cell leukemia affects younger patients, who present with poor general condition, fever, and disseminated disease; they often die within a short time from systemic disease or complications such as multi-organ failure.
  • The peripheral blood and bone marrow show atypical large granular lymphocytes, which exhibit an immunophenotype similar to that of extranodal NK/T-cell lymphoma.
  • Aggressive NK cell leukemia must be distinguished from T-cell large granular lymphocyte leukemia and indolent NK cell lymphoproliferative disorder, both of which are indolent.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Lymphoma / pathology
  • [MeSH-minor] Diagnosis, Differential. Humans. Lymphoma, T-Cell / diagnosis. Lymphoma, T-Cell / pathology. Lymphoma, T-Cell / therapy. Treatment Outcome

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  • (PMID = 12876671.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 99
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28. Suzuki R: Treatment of advanced extranodal NK/T cell lymphoma, nasal-type and aggressive NK-cell leukemia. Int J Hematol; 2010 Dec;92(5):697-701
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  • [Title] Treatment of advanced extranodal NK/T cell lymphoma, nasal-type and aggressive NK-cell leukemia.
  • Extranodal NK/T cell lymphoma, nasal type (ENKL) with advanced stage and aggressive NK-cell leukemia (ANKL) are highly aggressive neoplasms with a dismal clinical outcome.
  • It is well known that P-glycoprotein, which is a product of MDR1 gene and related to multi-drug resistance, is expressed on tumor cells of ENKL or ANKL.
  • However, recent studies have identified that several drugs including L: -asparaginase, methotrexate and alkylators show excellent effect for these tumors.
  • ANKL needs another treatment strategy because of a systemic disease progression and extensive organ insufficiency.
  • Optimal treatment scheme using such effective agents for these unfavorable NK-cell tumors should further be explored.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Killer Cells, Natural / pathology. Leukemia, T-Cell / therapy. Lymphoma, Extranodal NK-T-Cell / drug therapy
  • [MeSH-minor] Antineoplastic Agents / administration & dosage. Asparaginase / administration & dosage. Asparaginase / therapeutic use. Dexamethasone / administration & dosage. Drug Therapy, Combination. Etoposide / administration & dosage. Humans. Ifosfamide / administration & dosage. Methotrexate / administration & dosage. Treatment Outcome

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  • (PMID = 21116747.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; EC 3.5.1.1 / Asparaginase; UM20QQM95Y / Ifosfamide; YL5FZ2Y5U1 / Methotrexate
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29. Suzuki R, Suzumiya J, Nakamura S, Aoki S, Notoya A, Ozaki S, Gondo H, Hino N, Mori H, Sugimori H, Kawa K, Oshimi K, NK-cell Tumor Study Group: Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia; 2004 Apr;18(4):763-70
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  • [Title] Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells.
  • Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells.
  • Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline.
  • These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations.
  • Intensive treatment for ANKL may result in a better prognosis.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia, Lymphoid / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Anthracyclines / therapeutic use. Antigens, CD / analysis. Antineoplastic Agents / therapeutic use. Chromosome Aberrations. Female. Herpesvirus 4, Human. Humans. Immunophenotyping. Male. Middle Aged. Prognosis. Remission Induction. Retrospective Studies. Survival Analysis


30. Okamura T, Kishimoto T, Inoue M, Honda M, Yamashita N, Wakiguchi H, Yagita M, Hosoi G, Sako M, Yasui M, Yagi K, Kawa K: Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease. Bone Marrow Transplant; 2003 Jan;31(2):105-11
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease.
  • Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders, including chronic active EBV infection, EBV-associated hemophagocytic syndrome, hypersensitivity to mosquito bites, hydroa vacciniforme, aggressive NK-cell leukemia, and nasal/nasal-type NK-cell lymphoma.
  • In most instances, these disorders are refractory to conventional treatments and have a poor prognosis.
  • Here, we report a new treatment strategy for EBV-associated T/NK-cell LPD, consisting of immunochemotherapy, intensive combination chemotherapy, and stem cell transplantation.
  • The five patients studied, two with T-cell and three with NK-cell LPD, lacked a human leukocyte antigen-matched, related donor, and therefore received bone marrow grafts from HLA-matched, unrelated donors.
  • The preconditioning regimen consisted of total-body irradiation (12 Gy), etoposide (900 mg/m(2)), and cyclophosphamide (120 mg/kg) or melphalan (210 mg/m(2)).
  • Thus, UBMT appears to be a reasonable option for the treatment of patients with EBV-associated T/NK-cell LPD.
  • Detection of EBV-DNA by PCR offers an important tool for assessing minimal residual disease in patients with EBV-associated T/NK-cell LPD.
  • [MeSH-major] Bone Marrow Transplantation / methods. Herpesvirus 4, Human / isolation & purification. Killer Cells, Natural / immunology. Lymphoproliferative Disorders / therapy. T-Lymphocytes / immunology
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Combined Modality Therapy. DNA, Viral / genetics. DNA, Viral / isolation & purification. Drug Therapy, Combination. Female. Humans. Male. Polymerase Chain Reaction. Transplantation Conditioning / methods. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 12621491.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA, Viral
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31. Haran MZ, Basous L, Berrebi A: Multiple myeloma associated with CD4+ large granular lymphocytic leukemia: a possible causal relationship. Hematol J; 2004;5(5):458-60
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  • [Title] Multiple myeloma associated with CD4+ large granular lymphocytic leukemia: a possible causal relationship.


32. Ichikawa S, Fukuhara N, Yamamoto J, Suzuki M, Nakajima S, Okitsu Y, Kohata K, Onishi Y, Ishizawa K, Kameoka J, Harigae H: Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia. Intern Med; 2010;49(17):1907-10
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  • [Title] Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia.
  • Aggressive natural killer cell leukemia (ANKL) is a highly aggressive lymphoproliferative disease.
  • An appropriate therapeutic strategy for ANKL remains to be established, but a few case reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HCT) can be curative.
  • Here, we report a young woman with ANKL showing central nervous system (CNS) invasion, who has been in complete remission for more than a year after allo-HCT following two courses of intravenous chemotherapy and several rounds of intrathecal chemotherapy.
  • Intensive remission induction chemotherapy followed by conventional myeloablative allo-HCT is a promising approach for long-term remission in cases of this aggressive malignancy.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / surgery. Peripheral Blood Stem Cell Transplantation
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Asparaginase / administration & dosage. Brain / pathology. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Doxorubicin / administration & dosage. Epstein-Barr Virus Infections / virology. Etoposide / administration & dosage. Female. Herpesvirus 4, Human / isolation & purification. Humans. Ifosfamide / administration & dosage. Injections, Spinal. Leukemic Infiltration. Methotrexate / administration & dosage. Myeloablative Agonists / therapeutic use. Prednisone / administration & dosage. Remission Induction. Subarachnoid Hemorrhage / etiology. Subarachnoid Hemorrhage / radiography. Transplantation Conditioning. Transplantation, Homologous. Vincristine / administration & dosage

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  • (PMID = 20823655.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Myeloablative Agonists; 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; EC 3.5.1.1 / Asparaginase; UM20QQM95Y / Ifosfamide; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate; CHOP protocol
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33. Ma SY, Au WY, Chim CS, Lie AK, Lam CC, Tse E, Leung AY, Liang R, Kwong YL: Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients. Br J Haematol; 2004 Mar;124(6):754-61
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients.
  • The treatment results of indolent lymphoid malignancies in Chinese are poorly reported.
  • The efficacy of FND (fludarabine 25 mg/m2/d, x3; mitoxantrone 10 mg/m2/d, x1; dexamethasone 20 mg/d, x5; monthly cycles, x6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated.
  • For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50.5%, 18% and 68.5% respectively.
  • Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37.5%, P = 0.03; OR: 84% vs. 47.5%, P < 0.001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0.039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0.001).
  • For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months).
  • FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Prolymphocytic, T-Cell / drug therapy. Lymphoma, B-Cell / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Asian Continental Ancestry Group. Dexamethasone / administration & dosage. Dexamethasone / adverse effects. Disease-Free Survival. Female. Humans. Lymphoma, Non-Hodgkin / drug therapy. Lymphoma, Non-Hodgkin / ethnology. Male. Middle Aged. Mitoxantrone / administration & dosage. Mitoxantrone / adverse effects. Prospective Studies. Rituximab. Survival Analysis. Treatment Outcome. Vidarabine / administration & dosage. Vidarabine / adverse effects. Vidarabine / analogs & derivatives

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  • (PMID = 15009063.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 4F4X42SYQ6 / Rituximab; 7S5I7G3JQL / Dexamethasone; BZ114NVM5P / Mitoxantrone; FA2DM6879K / Vidarabine; FND protocol
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34. Manucha V, Zhao F, Rodgers W: Atypical lymphoid cells in cerebrospinal fluid in acute Epstein Barr virus infection: a case report demonstrating a pitfall in cerebrospinal fluid cytology. Acta Cytol; 2008 May-Jun;52(3):334-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • BACKGROUND: Cytologic examination of cerebrospinal fluid (CSF) continues to be important in the diagnosis of malignancies involving the leptomeninges.
  • A well-recognized pitfall is overinterpretation of the presence of atypical lymphocytes that resemble malignant lymphoid cells in the CSF.
  • A definite diagnosis is often difficult because of limited viability of cells and small sample size of CSF.
  • CASE: A 25-year-old patient with a past history of treated large granular lymphocytic leukemia and presence of a predominant population of large, atypical lymphoid cells in the CSF, giving us the impression of involvement with large cell lymphoma.
  • CONCLUSION: The presence of atypical cells in the CSF certainly warrants a detailed look at the patient's laboratory investigations and communication with the hematologist, because it may be the only specimen available for diagnosis on which therapy and prognosis is based.
  • [MeSH-major] Cerebrospinal Fluid / cytology. Cytological Techniques / methods. Epstein-Barr Virus Infections / cerebrospinal fluid. Epstein-Barr Virus Infections / pathology. Lymphocytes / pathology
  • [MeSH-minor] Adult. DNA, Viral / analysis. DNA, Viral / blood. Hepatomegaly / ultrasonography. Humans. Leukemia, Large Granular Lymphocytic / drug therapy. Lymph Nodes / pathology. Lymph Nodes / radiography. Lymphatic Diseases / pathology. Lymphatic Diseases / radiography. Male. Pleural Effusion / radiography. Splenectomy

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  • (PMID = 18540300.001).
  • [ISSN] 0001-5547
  • [Journal-full-title] Acta cytologica
  • [ISO-abbreviation] Acta Cytol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Viral
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35. O'Brien S, Ravandi F, Riehl T, Wierda W, Huang X, Tarrand J, O'Neal B, Kantarjian H, Keating M: Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy. Blood; 2008 Feb 15;111(4):1816-9
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  • [Title] Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy.
  • Median age was 58 years (range, 25-83 years); median number of prior therapies was 2 (range, 0-10).
  • Diagnoses included chronic lymphocytic leukemia (29), T-cell prolymphocytic leukemia (3), hairy cell leukemia (1), adult T-cell leukemia/lymphoma (ATLL) (1), marginal zone leukemia (1), large granular lymphocyte leukemia (2), acute lymphoblastic leukemia (1), and T-cell lymphoma (2).
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Antiviral Agents / therapeutic use. Cytomegalovirus / physiology. Cytomegalovirus Infections / prevention & control. Ganciclovir / analogs & derivatives. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Virus Activation / physiology
  • [MeSH-minor] Adolescent. Adult. Antibodies, Monoclonal, Humanized. B-Lymphocytes / drug effects. B-Lymphocytes / immunology. Female. Humans. Lymphocyte Depletion. Male. Patient Selection. T-Lymphocytes / drug effects. T-Lymphocytes / immunology

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  • [CommentIn] Blood. 2008 Sep 1;112(5):2167 [18725576.001]
  • (PMID = 18039954.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00562770
  • [Publication-type] Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 0 / Antiviral Agents; 0 / valganciclovir; 3A189DH42V / alemtuzumab; P9G3CKZ4P5 / Ganciclovir
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36. Epling-Burnette PK, Bai F, Wei S, Chaurasia P, Painter JS, Olashaw N, Hamilton A, Sebti S, Djeu JY, Loughran TP: ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL). Oncogene; 2004 Dec 9;23(57):9220-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL).
  • Chronic NK lymphoproliferative disease of large granular lymphocytes (LDGL) is characterized by the expansion of activated CD3-, CD16+ or CD56+ lymphocytes.
  • The mechanism of survival of NK cells from LDGL patients is unknown but may be related to antigenic stimulation.
  • There is currently no standard effective therapy for LDGL, and the disease is characteristically resistant to standard forms of chemotherapy.
  • We found evidence of constitutive activation of extracellular-regulated kinase (ERK) in NK cells from 13/13 patients with NK-LDGL (one patient with aggressive and 12 patients with chronic disease).
  • Ablation of ERK activity by inhibitors or a dominant-negative form of MEK, the upstream activator of ERK, reduced the survival of patient NK cells.
  • Ras was also constitutively active in patient NK cells, and exposure of cells to the Ras inhibitor FTI2153 or to dominant-negative-Ras resulted not only in ERK inhibition but also in enhanced apoptosis in both the presence and absence of anti-Fas.
  • Therefore, we conclude that a constitutively active Ras/MEK/ERK pathway contributes to the accumulation of NK cells in patients with NK-LDGL.
  • These findings suggest that strategies to inhibit this signaling pathway may be useful for the treatment of the NK type of LDGL.

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  • (PMID = 15516985.001).
  • [ISSN] 0950-9232
  • [Journal-full-title] Oncogene
  • [ISO-abbreviation] Oncogene
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA098472; United States / NCI NIH HHS / CA / CA83947; United States / NIAID NIH HHS / AI / AI052613; United States / NCI NIH HHS / CA / CA94872; United States / NCI NIH HHS / CA / CA83146; United States / NCI NIH HHS / CA / CA90633
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] EC 2.7.11.24 / Mitogen-Activated Protein Kinases
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37. Monjanel H, Hourioux C, Arbion F, Colombat P, Lissandre S, Regner MP, Senecal D: Rapid and durable molecular response of refractory T-cell large granular lymphocyte leukemia after alemtuzumab treatment. Leuk Res; 2010 Aug;34(8):e197-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Rapid and durable molecular response of refractory T-cell large granular lymphocyte leukemia after alemtuzumab treatment.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Drug Resistance, Neoplasm. Leukemia, Large Granular Lymphocytic / drug therapy. Salvage Therapy
  • [MeSH-minor] Antibodies, Monoclonal, Humanized. Humans. Male. Middle Aged. Remission Induction. Treatment Outcome

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  • (PMID = 20211489.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 3A189DH42V / alemtuzumab
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38. Go RS, Tefferi A, Li CY, Lust JA, Phyliky RL: Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia. Blood; 2000 Nov 15;96(10):3644-6
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  • [Title] Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia.
  • Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia.
  • Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3(+)/CD8(+)/CD57(+) cells in the bone marrow were found in most cases.
  • After a median follow-up of 49 months, 5 patients had died from the disease or related complications.
  • Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia.
  • [MeSH-major] Anemia, Aplastic / etiology. Leukemia, T-Cell / diagnosis
  • [MeSH-minor] Adult. Aged. Bone Marrow Cells / immunology. Cyclophosphamide / administration & dosage. Cyclophosphamide / standards. Cytogenetic Analysis. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Immunophenotyping. Immunosuppressive Agents / administration & dosage. Immunosuppressive Agents / standards. Leukemia, Lymphoid / complications. Leukemia, Lymphoid / diagnosis. Leukemia, Lymphoid / drug therapy. Lymphoproliferative Disorders / complications. Lymphoproliferative Disorders / diagnosis. Lymphoproliferative Disorders / drug therapy. Male. Middle Aged. Prednisone / administration & dosage. Prednisone / standards. Survival Rate. Treatment Outcome

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  • (PMID = 11071666.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone
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39. Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F, Hjorth-Hansen H, Höglund M, Kovanen P, Laurinolli T, Liesveld J, Paquette R, Pinilla-Ibarz J, Rauhala A, Shah N, Simonsson B, Sinisalo M, Steegmann JL, Stenke L, Porkka K: Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia; 2009 Aug;23(8):1398-405
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  • [Title] Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy.
  • Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses.
  • We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy.
  • An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy.
  • Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype.
  • All T-cell expansions were clonal.
  • Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis.
  • Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia.
  • In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Killer Cells, Natural / drug effects. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Lymphocytosis / chemically induced. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Protein Kinase Inhibitors / pharmacology. Pyrimidines / pharmacology. T-Lymphocyte Subsets / drug effects. T-Lymphocytes, Cytotoxic / drug effects. Thiazoles / pharmacology

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  • [CommentIn] Acta Haematol. 2016;136(4):219-228 [27656875.001]
  • (PMID = 19295545.001).
  • [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 / Antineoplastic Agents; 0 / Neoplasm Proteins; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Thiazoles; RBZ1571X5H / Dasatinib
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40. Maruo T, Namikawa K, Kunihiro A, Lynch J, Shida T, Kishikawa S: Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog. J S Afr Vet Assoc; 2009 Dec;80(4):261-3
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  • [Title] Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog.
  • Findings from the complete blood count revealed a marked lymphocytosis (113000/ml).
  • Examination of Wright-Giemsa-stained films of peripheral blood revealed the presence of large granular lymphocytes (LGL).
  • Seventy-two per cent (81360/ml) of the lymphocytes were found to be 12-17 microm in diameter, containing nuclei with mature clumped chromatin and abundant lightly basophilic cytoplasm with a variable number of fine azurophilic granules.
  • Based on these findings this case was diagnosed as LGL leukaemia.
  • As a result of multiple-agent chemotherapy, the markedly elevated levels of lymphocytes gradually decreased to 7500/ml on day 122 and the patient maintained a good quality of life for the following 3 months.
  • Shortly after diagnosis, the dog developed sudden onset of central nervous system signs and died on day 270.
  • A common outcome of canine LGL is the development of acute blast crisis or lymphoma.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Histiocytic Sarcoma / veterinary. Leukemia, Large Granular Lymphocytic / veterinary
  • [MeSH-minor] Animals. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Dog Diseases. Dogs. Fatal Outcome. Male

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  • (PMID = 20458870.001).
  • [ISSN] 1019-9128
  • [Journal-full-title] Journal of the South African Veterinary Association
  • [ISO-abbreviation] J S Afr Vet Assoc
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] South Africa
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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41. Kwong YL: Natural killer-cell malignancies: diagnosis and treatment. Leukemia; 2005 Dec;19(12):2186-94
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  • [Title] Natural killer-cell malignancies: diagnosis and treatment.
  • Natural killer (NK)-cell malignancies are uncommon diseases.
  • Previously known as polymorphic reticulosis or angiocentric T-cell lymphomas, they are classified by the World Health Organization as NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia.
  • Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with an angioinvasive and angiodestructive pattern.
  • T-cell receptor gene is germline, and clonal Epstein-Barr virus (EBV) infection is almost invariably.
  • Clinically, they can be divided into nasal, non-nasal, and aggressive lymphoma/leukemia subtypes.
  • Most nasal NK-cell lymphomas present with stage I/II disease, and frontline radiotherapy is the most important key to successful treatment.
  • Many stage I/II patients treated with radiotherapy fail systemically, implying that concomitant chemotherapy may be needed.
  • Chemotherapy is indicated for advanced nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes.
  • However, treatment results are unsatisfactory.
  • High-dose chemotherapy with hematopoietic stem cell transplantation may be beneficial to selected patients.
  • The International Prognostic Index and presentation EBV DNA load is of prognostic significance and may be useful in the stratification of patients for various treatment modalities.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia. Lymphoma
  • [MeSH-minor] Combined Modality Therapy. Herpesvirus 4, Human. Humans. Treatment Outcome

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  • (PMID = 16179910.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Number-of-references] 83
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42. Moosig F, Schoch R, Kneba M: [T-large granular lymphocyte leukaemia. An important differential diagnosis to Felty's syndrome]. Z Rheumatol; 2006 Sep;65(5):447-51
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [T-large granular lymphocyte leukaemia. An important differential diagnosis to Felty's syndrome].
  • [Transliterated title] Die T-large Granular Lymphocyte Leukämie (T-LGL-Leukämie). Eine wichtige Differenzialdiagnose zum Felty-syndrom.
  • T-Large Granular Lymphocyte (T-LGL) leukaemia is a rare clonal disease characterized by neutropenia and/or anaemia.
  • Because of its strong association with rheumatoid arthritis (RA), T-LGL leukaemia is an important differential diagnosis to Felty's syndrome.
  • This differentiation might be especially difficult since, in severe RA with extraarticular manifestations, there is often an expanded memory effector T-cell population which can hardly be separated from T-LGL leukaemia cells by means of immunophenotyping.
  • The main criterion for T-LGL leukaemia is the detection of a clonal T-cell-receptor rearrangement by PCR.
  • First-line therapy consists of weekly low-dose methotrexate.
  • There are very limited data from therapy studies.
  • The German CLL study group has initiated a protocol using parenteral low-dose methotrexate as first-line therapy and fludarabine as second-line medication.
  • [MeSH-major] Leukemia, Lymphoid / diagnosis. Leukemia, T-Cell / diagnosis
  • [MeSH-minor] Antirheumatic Agents / therapeutic use. Antiviral Agents / therapeutic use. Arthritis, Rheumatoid / diagnosis. Arthritis, Rheumatoid / drug therapy. Diagnosis, Differential. Felty Syndrome / diagnosis. Humans. Immunosuppressive Agents / therapeutic use. Methotrexate / therapeutic use. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use

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  • (PMID = 16450150.001).
  • [ISSN] 0340-1855
  • [Journal-full-title] Zeitschrift fur Rheumatologie
  • [ISO-abbreviation] Z Rheumatol
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antirheumatic Agents; 0 / Antiviral Agents; 0 / Immunosuppressive Agents; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; YL5FZ2Y5U1 / Methotrexate
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43. Ino K, Masuya M, Nakamori Y, Suzuki K, Mizutani M, Sekine T, Yamaguchi M, Nakase K, Kaida K, Ogawa H, Katayama N: [Aggressive NK-cell leukemia with sustained relapse-free survival after allogeneic peripheral blood stem cell transplantation]. Rinsho Ketsueki; 2010 Apr;51(4):258-63
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  • [Title] [Aggressive NK-cell leukemia with sustained relapse-free survival after allogeneic peripheral blood stem cell transplantation].
  • A bone marrow examination showed several hemophagocytic macrophages, and a diagnosis of hemophagocytic syndrome was made.
  • A repeat bone marrow examination demonstrated that 28.4% of marrow nucleated cells were atypical lymphocytes, which were positive for CD2, CD7, CD16, CD56, and HLA-DR.
  • Clonality of these proliferating NK cells was confirmed by an analysis of EB virus terminal repeat sequence and cytogenetic analysis, and final diagnosis of aggressive NK-cell leukemia was made.
  • After induction chemotherapy consisting of dexamethasone, etoposide, ifosfamide, and L-asparaginase, the patient achieved partial remission.
  • He received allogeneic peripheral blood stem cell transplantation from his one locus mismatched son, and is alive with no evidence of disease 20 months after transplantation.
  • [MeSH-major] Killer Cells, Natural. Leukemia, Lymphoid / therapy. Peripheral Blood Stem Cell Transplantation
  • [MeSH-minor] Antigens, CD. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Disease-Free Survival. Herpesvirus 4, Human / genetics. Humans. Male. Middle Aged. Remission Induction. Terminal Repeat Sequences. Transplantation, Homologous


44. Mohan SR, Clemente MJ, Afable M, Cazzolli HN, Bejanyan N, Wlodarski MW, Lichtin AE, Maciejewski JP: Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia. Haematologica; 2009 Oct;94(10):1407-14
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  • [Title] Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia.
  • BACKGROUND: T-cell large granular lymphocytic leukemia is a clonal proliferation of cytotoxic T-lymphocytes which often results in severe cytopenia.
  • Current treatment options favor chronic immunosuppression.
  • Alemtuzumab, a humanized monoclonal antibody against glycophosphatidylinositol-anchored CD52, is approved for patients refractory to therapy in other lymphoid malignancies.
  • DESIGN AND METHODS: We retrospectively examined treatment outcomes in 59 patients with CD8+ T-cell large granular lymphocytic leukemia, 41 of whom required therapy.
  • Eight patients with severe refractory cytopenia despite multiple treatment regimens had been treated with subcutaneous alemtuzumab as salvage therapy.
  • Flow cytometry was used to monitor expression of glycophosphatidylinositol-anchored CD52, CD55, and CD59 as well as to characterize T-cell clonal expansions by T-cell receptor variable beta-chain (Vbeta) repertoire.
  • RESULTS: Analysis of the effects of alemtuzumab revealed remissions with restoration of platelets in one of one patient, red blood cell transfusion independence in three of five patients and improvement of neutropenia in one of three, resulting in an overall response rate of 50% (4/8 patients).
  • Clonal large granular lymphocytes exhibited decreased CD52 expression post-therapy in patients refractory to treatment.
  • Samples of large granular lymphocytes collected prior to therapy also unexpectedly had a significant proportion of CD52-negative cells while a healthy control population had no such CD52 deficiency (p=0.026).
  • CONCLUSIONS: While alemtuzumab may be highly effective in large granular lymphocytic leukemia, prospective serial monitoring for the presence of CD52-deficient clonal cytotoxic T-lymphocytes should be a component of clinical trials investigating the efficacy of this drug.
  • CD52 deficiency may explain lack of response to alemtuzumab, and such therapy may confer a survival advantage to glycophosphatidylinositol-negative clonal cytotoxic T-lymphocytes.

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  • [CommentIn] Haematologica. 2009 Oct;94(10):1341-5 [19794080.001]
  • (PMID = 19794084.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA113972; United States / NCRR NIH HHS / RR / U54 RR019397; United States / NCRR NIH HHS / RR / U54 RR 019397
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / CD52 antigen; 0 / Glycoproteins; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ PMC2754957
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45. Dearden CE, Matutes E, Catovsky D: Alemtuzumab in T-cell malignancies. Med Oncol; 2002;19 Suppl:S27-32
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  • [Title] Alemtuzumab in T-cell malignancies.
  • Alemtuzumab is a humanized monoclonal antibody directed against the CD52 antigen, which is abundantly expressed on all normal and most malignant T-lymphocytes.
  • We summarize the results of our experience using alemtuzumab to treat a range of clinically aggressive, mature, post-thymic, T-cell malignancies, including T-cell prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), T-cell large granular lymphocyte (T-LGL) leukemia, and human T-cell lymphotropic virus I (HTLV-I) associated adult T-cell leukemia-lymphoma (ATLL).
  • Alemtuzumab was administered at a dose of 30 mg, three times a week until maximum response.
  • Apart from first-dose reactions, which were common, treatment was well tolerated, the main complication being infection and viral reactivation associated with the prolonged lymphopenia.
  • Overall response rates were 76% (60% complete response) in 39 patients with T-PLL and 100% in 3 patients with CTCL, of duration up to 4 yr.
  • Experience in T-LGL and ATLL is limited to single cases only and further studies are required to better define the role of alemtuzumab in these subgroups.
  • Our results indicate that alemtuzumab has activity in T-cell malignancies, particularly in T-PLL and in patients with predominantly blood and bone marrow disease.
  • It may be possible to prolong response duration by the use of high-dose therapy and stem cell transplantation.
  • Alemtuzumab may also have a role in purging minimal residual disease following other chemotherapy and prior to transplantation.
  • We conclude that treatment with alemtuzumab may offer new hope to patients who otherwise have a bleak prognosis.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antigens, CD / drug effects. Antigens, Neoplasm / drug effects. Antineoplastic Agents / therapeutic use. Glycoproteins / drug effects. Lymphoma, T-Cell / drug therapy

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  • (PMID = 12180489.001).
  • [ISSN] 1357-0560
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / Antineoplastic Agents; 0 / CD52 antigen; 0 / Glycoproteins; 3A189DH42V / alemtuzumab
  • [Number-of-references] 18
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