A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia

The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m²/day × 5 days as an infusion and mitoxantrone, 10 mg/m²/day × 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-α (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived ≥1 year. Toxicity was primarily hematologic. The objective response rate was 61% (8/13) among those who did not die TETE and 40% among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.