COMPLETE HEMATOLOGIC REMISSIONS IN CHRONIC-PHASE, PHILADELPHIA-CHROMOSOME-POSITIVE, CHRONIC MYELOGENOUS LEUKEMIA AFTER 2-CHLORODEOXYADENOSINE

Background. 2-Chlorodeoxyadenosine (Cladribine, Leustatin, Ortho Biote ch, Raritan, NJ) (2-CdA) is a purine analog with activity in the treat ment of lymphoid neoplasms. Interferon induces cytogenetic remissions in chronic myeloid leukemia (CML) and partial remissions in hairy cell leukemia, a disorder in which single courses of 2-CdA induce complete remissions. In vitro clonal growth of immature myeloid progenitors fr om normal marrow is markedly inhibited by 2-CdA.Methods. 2-CdA was adm inistered to 12 patients with Philadelphia-chromosome-positive CML, 11 chronic phase, and 1 accelerated phase, at 0.1 mg/kg/day by continuou s intravenous infusion for 7 days every 28-35 days, until maximum peri pheral hematologic response. Results. Of 12 patients, 10 (83%) achieve d complete hematologic responses and 2 (17%) partial hematologic respo nses after a median of two courses of 2-CdA. The median first hematolo gic response duration was 3 months. Of the seven patients who relapsed and were retreated with a median of two further courses of 2-CdA, fiv e obtained responses (four complete and one partial) and two did not r espond. The median second hematologic response duration was 4 months. No patient had significant Philadelphia-chromosome suppression. Revers ible myelosuppression and severe cumulative T-cell immunosuppression a ssociated with opportunistic infections in four patients were the prin cipal toxicities. Conclusions. 2-CdA is active in CML, inducing comple te hematologic responses, but the absence of cytogenetic responses and severe immunosuppression may limit its clinical use.