nelarabine and Neutropenia

The Cancer and Leukemia Group B (CALGB) has performed a series of studies evaluating different aspects of remission induction and postremission treatment in adults with acute lymphocytic leukemia (ALL). In recent years, these clinical trials have been supplemented by systematic morphologic, immunophenotyping, cytogenetic, and molecular genetic studies leading to the identification of different risk groups of patients who may warrant individualized treatments. These protocols have enrolled all adult patients older than 15 years with ALL, without an upper age restriction, and did not exclude Philadelphia (Ph) chromosome-positive patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Asparaginase; Bacterial Proteins; Cell Lineage; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Disease-Free Survival; Escherichia coli; Follow-Up Studies; Humans; Immunophenotyping; Lymphoma, Non-Hodgkin; Middle Aged; Multicenter Studies as Topic; Neutropenia; Philadelphia Chromosome; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Remission Induction; Risk; Survival Analysis; Treatment Outcome; United States

Nelarabine (506U78) is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m(2)/day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL.

Topics: Adolescent; Adult; Aged; Arabinonucleosides; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Salvage Therapy; Survival Analysis; Thrombocytopenia; Treatment Outcome