Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial

Abstract

Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.

The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach

“…The latter applies to most patients with the so-called core binding factor leukemias-AML t(8;21), and AML inv(16)/t(16;16). Meanwhile, continued study of alloHSCT in intermediate risk AML is warranted, because of a continuous trend of progessiviely improved survival following autologous HSCT and/or chemotherapy as consolidation therapy (15)(16)(17)(18).…”

“…While that discussion is underpinned with mature survival data from a number of studies, late, persistent morbidity and quality of life were not taken into account. However, this issue cannot be disregarded especially when chemotherapeutic approaches and/or autologous HSCT, which 15 are associated with less morbidity continue to improve outcome in intermediate risk AML (15)(16)(17)(18). Several studies in recipients of alloHSCT have addressed the issue of late morbidity and late mortality occurring in patients, who were alive and well at 2 years after alloHSCT (102)(103)(104)(105)(106).…”

Improved outcome of patients with low‐ and intermediate‐risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine

“…26 This was suggested also by the MRC15 trial results, which showed a benefit of GO in patients treated with FLAG-Ida. 22 Moreover, a recent publication 26 reported in vitro synergy between mitoxantrone and GO, which was used in combination with GO in 64% of the patients in our study.…”

“…However, there are no conclusive data supporting a real difference of outcome between intermediate-and high-dose AraC alone. 22,23 Recently, disappointing results from frontline comparative studies testing the addition of GO to induction/ consolidation chemotherapy in previously untreated patients have been reported. 22,24,25 How can we explain the differences with our results?…”

Questions regarding frontline therapy of acute myeloid leukemia

“…They observed that the addition of GO improved outcome in selected patient subsets. 20 Overall, the results from multiple investigations using different induction approaches (high-dose cytarabine induction; high-dose daunorubicin induction; idarubicin instead of daunorubicin; the addition of GO, chlorodeoxyadenosine, or lomustine) suggest that better regimens than ''3 þ 7 regimens'' are available. These regimens should be investigated further in the context of AML heterogeneity and the emerging prognostic knowledge concerning cytogenetic and molecular abnormalities (FLT3 abnormalities, nucleophosmin [NPM1] mutations, others) and the properties of the AML stem cell.…”