pentostatin and Leukemia--Large-Granular-Lymphocytic

T-cell large granular lymphocytic leukaemia (T-LGLL) is an incurable leukaemia characterised by clonal proliferation of abnormal cytotoxic T cells that can result in severe neutropenia, transfusion-dependent anaemia and pancytopenia requiring treatment. The most commonly used agents, methotrexate (MTX), cyclophosphamide (Cy) and cyclosporine primarily produce partial remissions (PRs), with few complete responses (CRs). We evaluated the clinical course and treatment response of 60 consecutive patients with T-LGLL to evaluate clinical outcomes and future potential treatment directions. Impaired overall survival was noted among male patients, patients with elevated lactate dehydrogenase, and those without rheumatoid arthritis. Cy was the most efficacious second-line agent, with a 70% overall response rate (ORR; three CR, four PR). All patients who failed frontline MTX responded to second-line Cy. In the relapsed or Cy-refractory setting, alemtuzumab (n = 4) and pentostatin (n = 3) had an ORR of 50% and 66%, respectively, while duvelisib induced a long-term response in one patient. In this large, retrospective analysis, our results suggest Cy is a highly effective therapy for second-line treatment in T-LGLL and should be considered a strong candidate for up-front therapy in select high-risk patients. Prospective studies evaluating pentostatin, alemtuzumab and novel agents, such as duvelisib, are needed for patients with relapsed/refractory T-LGLL.

Topics: Aged; Alemtuzumab; Antineoplastic Agents; Cyclophosphamide; Cyclosporine; Female; Follow-Up Studies; Humans; Leukemia, Large Granular Lymphocytic; Male; Methotrexate; Middle Aged; Pentostatin; Prognosis; Retrospective Studies

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.

Topics: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Leukemia, Large Granular Lymphocytic; Male; Methotrexate; Middle Aged; Pentostatin; Survival Rate; Treatment Outcome

We report a 25-year-old woman with T-cell large granular lymphocytic leukaemia presenting with severe neutropenia, anaemia and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+, TCRgamma delta+, CD4-, CD5+, CD7+, CD8+, CD57+ large granular lymphocytes. Clonality was demonstrated with T-gamma polymerase chain reaction analysis which revealed clonal rearrangement of the TCRgamma chain gene. Cyclosporine, granulocyte colony-stimulating factor, methothrexate and a combination of cyclophosphamide, vincristine and prednisolone failed to correct the neutropenia and the anaemia. Finally, treatment with 2-deoxycoformycin resulted in both clinical and haemotological complete responses, despite molecular evidence of the persistence of the abnormal T-cell clone.

Topics: Adult; Antineoplastic Agents; Female; Humans; Leukemia, Large Granular Lymphocytic; Pentostatin