HEMATOLOGIC REMISSION AND CYTOGENETIC IMPROVEMENT AFTER TREATMENT OF STABLE-PHASE CHRONIC MYELOGENOUS LEUKEMIA WITH CONTINUOUS-INFUSION OF LOW-DOSE CYTARABINE

Prolonged exposure to low concentrations of cytarabine preferentially inhibits in vitro growth of neoplastic myeloid progenitors from patien ts with chronic myelogenous leukemia (CML) compared to that of normal myeloid progenitors. Continuous infusions of cytarabine in doses of 15 -30 mg/m2/day were therefore administered for extended periods to pati ents with CML in stable phase to determine if this treatment could ach ieve selective cytoreduction of Philadelphia chromosome (Ph)-positive cells. Five patients demonstrating > 90% Ph-positive metaphases before treatment received a total of 43 cycles of cytarabine infusional ther apy. Cytarabine was administered on an outpatient basis using a portab le, battery-operated syringe pump until the total leukocyte count reac hed 2500/mul or the platelet count reached 75,000/mul. A new cycle was begun when the total leukocyte count exceeded 4,000/mul and the plate let count exceeded 100,000/mul. The median duration of cytarabine admi nistration per cycle was 29 days (range 15-72 days). Leukocytosis was readily controlled by low-dose cytarabine therapy in all patients. All five patients experienced complete hematologic responses during cytar abine therapy. The fraction of Ph-positive metaphases in the marrow of the five patients was reduced to 0, 10%, 43%, 72%, and 84%, respectiv ely, during therapy. The median time to achieve optimal cytogenetic re sponse was 4.8 months (range 2.8-8.6 months). One patient demonstrated a complete cytogenetic response after three cycles of cytarabine. Ano ther patient demonstrated persistent cytogenetic improvement during 20 cycles of cytarabine, with a median 38% Ph-positive marrow metaphases (range 10-53%) over 32 months. Cytarabine therapy was generally well- tolerated, but was discontinued in one patient because of persistent a symptomatic elevations in hepatic enzymes, which resolved within 2 mon ths after discontinuing therapy. There were no episodes of fever durin g neutropenia, and platelet transfusions were not required. However, s ymptomatic anemia requiring transfusion of red cells occurred during m ost cycles of treatment. In summary, treatment of CML with low-dose cy tarabine can induce prolonged cytogenetic improvement in some patients with acceptable toxicity. Further evaluation is needed to ascertain t he effects of this treatment on duration of stable phase and overall s urvival.