Optimal induction and post-remission therapy for acute myeloid leukemia

Abstract

The approach to treatment of acute myeloid leukemia is substantially influenced by the age of the patient. Younger patients who are arbitrarily defined as those being o60 years, although comprising the minority of all patients with the disease, will always receive an intensive approach, whereas in older patients, an initial decision as to whether an intensive approach is appropriate or not has to be made. Standard chemotherapy for many years has been '3 þ 7', followed by consolidation with high-dose Ara-C at a daily dose level of 3 g/m 2 . It remains unclear as to what number of total treatment courses is optimal. Alternatives to this standard of care will be considered.Leukemia Supplements (2012) 1, S14--S15; doi:10.1038/leusup.2012.10Keywords: acute myeloid leukemia; induction; dose; immunoconjugate; consolidation; chemotherapy INDUCTION Daunorubicin doseThe question of whether daunorubicin (DA) should remain as a standard has been asked in randomized comparisons with idarubicin or mitoxantrone in several randomized trials without convincing evidence for substantial differences in survival being seen. There has always been an issue regarding dose equivalence of DA at doses of 45 mg/m 2 and 50 mg/m 2 . Recent studies have raised the issue of dose intensification of DA either by dose escalation to a 90-mg dose or daily dosing for 5 days. The E1900 trial, 1 which has been undertaken by the Eastern Cooperative Oncology Group in 657 younger patients, compared a DA dose of 90 mg/m 2 versus 45 mg/m 2 in a 3 þ 7 schedule for the first induction course. For those not in remission with course 1, an additional DA-containing course was recommended (with a 45 mg/m 2 dose). The higher doses achieved a higher overall remission rate (70% vs 56%, P ¼ o0.001) with more in complete remission (CR) after course 1 (83% vs 72%), and a better overall survival (23.7 months vs 15.7 months; P ¼ 0.003). A similar approach was taken by the HOVON-SAKK group 2 in older patients. In this study, the overall remission rate was similarly improved (64% vs 54%; P ¼ 0.002), but overall survival did not improve, except in patients in the 60-to 65-year subgroup (38% vs 23%).These data receive further support from a Korean trial 3 in 383 younger patients, in which the daunorubicin was intensified by giving DA (90 mg/m 2 vs 45 mg/m 2 ) by continuous infusion over 3 days which was also superior in the higher dose arm, CR 82% versus 72% (P ¼ 0.014)and overall survival 47% versus 35% (P ¼ 0.03).There has been discussion for a long time about dose equivalence between DA and alternatives such as idarubicin. A study from the French ALFA group 4 compared the effect of DA at a dose of 80 mg/m 2 on days 1 to 3 with idarubicin at a dose of 12 mg/m 2 for either 3 or 4 consecutive days in patients aged 50--70 years. In 468 randomized patients, idarubicin treatment for 3 or 4 days produced more remissions than DA (83% vs 78% vs 70%; P ¼ 0.04); however, this did not result in any difference in survival. A recent Japanese trial 5 in 1057 younger patients tested inte...

Survival of Patients with Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: An Experience in Developing Country

“…Post-remission therapy in patients with AML may consist of continuing chemotherapy or transplantation using either autologous or allogeneic stem cells 8 . Data on cytogenetic abnormalities and somatic mutations has provided important information that is essential for therapeutic decision making 9 . Patients with AML can be classified into three prognostic groups based on cytogenetic; good, intermediate, and high-risk [ 10 , 11 ].…”