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.
KeywordsAcute Myeloid Leukemia Complete Remission Complete Remission Rate Acute Nonlymphocytic Leukemia Refractory Acute Myeloid Leukemia
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- 2.Hiddemann W, Martin WR, Sauerland CM, Hei-necke A, Buchner T (1990) Definition of refractoriness against conventional chemotherapy in acute myeloid leukemia: a proposal based on the results of retreatment by thioguanine, cytosine arabinoside, and daunorubicin (TAD 9) in 150 patients with relapse after standardized first line therapy. Leukemia 4: 184–188PubMedGoogle Scholar
- 4.Bloomfield CD, Lawrence D, Arthur DC, Berg DT, Schiffer CA, Mayer RJ (1994) Curative impact of intensification with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) varies by cytogenetic group. Blood 81 (Suppl 1): 111aGoogle Scholar
- 5.to Boekhorst P, Löwenberg B, van Kapel J, Noo-ter K, Sonneveld P (1995) Multidrug resistant cells with high proliferative capacity determine response to therapy in acute myeloid leukemia. Leukemia 9: 1025–1031Google Scholar
- 12.Reed E (1993) Platinum analogs. In: De Vita VT Jr, Hellman S, Rosenberg ST (eds) Cancer. Principles and practice of oncology. Lippincott, Philadelphia, pp 390–400Google Scholar
- 22.Bonanad S, Blanquer A, Martin G, Martinez J, Sanz JF, Sanz MA (1994) Carboplatin-based regimens for treatment of myelodisplastic syndromes (MDS) and secondary acute myeloblastic leukemias (S-AML). Br J Haematol 87 (Suppl 1): 3Google Scholar
- 23.Bonanad S, Blanquer A, Martin G, Martinez J, Senent L, Sanz MA (1994) Carboplatin plus ARA-C in the treatment of high-risk acute myeloid leukemia. BR J Haematol 87 (Suppl 1): 4Google Scholar
- 24.Spiers A, Ballester O, Saba H et al. (1994) The CADET regimen (carboplatin/Ara-C/daunorubicin/etoposide/thioguanine): an active combination in poor prognosis acute myeloid leukemia ( AML ). Proc ASCO 13: 307Google Scholar
- 26.Reiffers J, Attal M, Michallet M et al. (1995) Comparison of allogenic bone marrow transplantation, autologous stem cell transplantation and chemotherapy in patients with acute myeloid leukemia (AML) in first remission: the BGMT experience. Bone Marrow Transplant 15 (Suppl 2): S54Google Scholar