Carboplatin-Based High-Dose Therapy for Refractory Acute Myeloid Leukaemia
A combination of carboplatin plus high-dose ara-C and either mitoxantrone or idarubicin (crossover) was used in 26 adults with refractory or relapsed AML and the following high-risk features: primary refractory 38%, > 2nd relapse 23%, 1st CR < 12 mos. 11%, age > 60 years 19%, FAB M5/secondary AML 23%, prior high-dose ara-C 35%, prior bone marrow transplant 27%. The first regimen (12 patients) with carboplatin 300 mg/m2/d (24-hour infusion) on days 1–4, high-dose ara-C 1 g/m2/bd on days 1–5, mitoxantrone (idarubicin) 12 (6) mg/m2/d on days 1–3 was highly toxic resulting in the early death of 7 patients. With a reduced intensity regimen (14 patients) consisting of carboplatin as above, high-dose ara-C on alternate days (1, 3, 5), and mitoxantrone (idarubicin) reduced to 8 (5) mg/m2/dose, the response rate was 64% (7 complete and 2 partial remissions). Complete remissions were consolidated with lower-intensity chemotherapy and autologous (n = 5) or allogeneic (n = 2) bone marrow/peripheral blood cell transplants. Overall survival was 2.1 months, responders living longer (median 11 months, 2-year probability 0.34) than nonresponders (p < 0.001). The second carboplatin-based regimen was effective in the management of patients with advanced-stage AML and ≤2 high-risk features. Mobilization of CD34+ circulating blood cells for autografting was possible and a prolonged remission was obtained in some of these patients.
KeywordsToxicity Leukemia Etoposide Cytosine Carboplatin
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