pentostatin and Leukopenia

Eighty-five hairy cell leukemia (HCL) patients who had failed initial therapy with recombinant alpha interferon were enrolled for pentostatin therapy. All had HCL confirmed by central pathology review and were eligible for evaluation. The median age was 55 years (range 31-83 years). Fifteen patients were between 31- and 40-years-old. There were 72 males (85%) and 13 females (15%). Fifty-four patients (64%) had prior splenectomy. All had been previously treated with interferon; nine had achieved a complete response (CR), 36 had a partial response (PR), 35 had stable disease (SD), and five patients had progressive disease. Patients with a CALGB performance status (PS) of 0-2 (78 patients) received 4 mg/m2 i.v. on days 1 and 15, repeated every 4 weeks. Patients with a performance status of 3 or 4 (seven patients) were started at 2 mg/m2 i.v. in the absence of grade 3 toxicity, the dose was escalated. Complete responses were seen in 36 patients (42.4%) and 35 patients had partial responses (41.2%) for an overall response rate of 83.6%. Median time to best response was 6.5 months. Eight patients had stable disease, and one patient had progressive disease. Three patients died early during the treatment phase and two were not evaluable due to treatment violations. Of seven patients with a CALGB performance status of 3 or 4, there were no CRs and only two PRs. Of 31 evaluable PS 0-2 patients who had previously achieved only stable disease on interferon, 13 had a CR on pentostatin and 12 had a PR. Based on PS 0-2 patients, the median follow-up is 44 months and 36 month remission duration and survival rates and 95% confidence intervals are 84% (CI 68-93%) and 91% (CI 81-96%). The 36 month survival rate was 29% (CI 10-58%) for PS 3-4 patients. Drug dosage was modified in 39 (51%) of 76 evaluable patients. Leukopenia and/or infection were the most frequent toxicities leading to a dose modification. Pentostatin is an effective agent and induces an excellent response in relapsed HCL patients previously treated with alpha-interferon (alpha-IFN).

Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Interferon Type I; Leukemia, Hairy Cell; Leukopenia; Male; Middle Aged; Pentostatin; Recombinant Proteins; Remission Induction; Survival Rate; Thrombocytopenia; United States

The immune function of patients with hairy cell leukemia (HCL) and solid tumors was evaluated before and after treatment with the investigational drug 2'-deoxycoformycin (pentostatin; dCF). Thirteen HCL patients received doses of dCF of 2 to 4 mg/m2 intravenously at 2- to 6-week intervals for up to 15 courses. After completion of treatment, 12 of 13 patients had resolution of severe monocytopenia and five of nine had normal monocyte antibody dependent cellular cytotoxicity. There was statistically significant depression of total lymphocytes, T cells, and B cells. Evaluation of T subsets showed a decrease in CD4+ cells. Immunoglobulin G (IgG) in sera were decreased from baseline, while IgM and IgA were unaffected. There was no significant effect on skin-test reactivity or large granular lymphocyte numbers. Lymphoblastic transformation was variably affected. Natural-killer (NK) cell function was improved or unchanged after dCF treatment. Reevaluation of seven patients at 21 to 119 weeks after receiving dCF demonstrated that recovery to normal T- and B-cell numbers and subsets does occur. Five solid tumor patients were given dCF at 4 mg/m2 intravenously at 1- to 2-week intervals for up to five courses. There was significant reduction in T cells, B cells, CD4+, and CD8+ cells with no statistically significant effect on the other immune parameters. We conclude that low doses of dCF can cause persistent immunosuppression though recovery may occur after the drug is stopped. In patients followed after completion of dCF, there was no associated increase in second malignancies or unusual infections.

Topics: Antibody-Dependent Cell Cytotoxicity; B-Lymphocytes; Humans; Immune Tolerance; Killer Cells, Natural; Leukemia, Hairy Cell; Leukocyte Count; Leukopenia; Lymphocyte Activation; Neoplasms; Pentostatin; Prospective Studies; T-Lymphocytes

We have investigated the use of 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase (ADA), in the treatment of 4 patients with advanced mycosis fungoides (MF). Since DCF has demonstrated an adverse effect in vitro and in vivo on the survival of leukemia T-cell lines, it appeared reasonable to examine its effect in patients with advanced cutaneous T-cell lymphoma. A total of 8 courses of DCF were given to the 4 patients. Since this study was part of an ongoing phase I investigation, each patient received a fixed dose (varying from 4 mg/sq m to 10 mg/sq m daily for 3 consecutive days) on a 28-day schedule. One patient had reversible renal insufficiency. Three patients had reversible myelosuppression. Two patients had a complete remission of disease for 7+ and 9+ mo. respectively. Two additional patients had partial remissions for 4 and 9 mo, respectively. We concluded that effective antitumor activity in advanced MF can be achieved with DCF at doses that may not be associated with prohibitive toxicity. We would encourage further investigation of this agent in patients with advanced cutaneous T-cell lymphoma.

Topics: Adenosine Deaminase; Coformycin; Humans; Immunosuppression Therapy; Kidney Diseases; Leukopenia; Mycosis Fungoides; Pentostatin; Ribonucleosides