Optimizing the conditioning regimen for allogeneic stem-cell transplantation in acute myeloid leukemia; Dose intensity is still in need

Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in AML by providing both dose-intensive chemo-radiotherapy and induction of graft-versus-leukemia (GvL) effect. Historically, more emphasis was given to the intensity of conditioning. Over the last decade the pendulum turned more towards induction of GvL as the primary goal. A plethora of non-myeloablative (NMA) and reduced-intensity conditioning regimens (RIC) were introduced trying to reduce transplant-related toxicities and allow SCT in elderly and medically infirm patients. In addition, reduced-toxicity myeloablative regimens (RTC) based on fludarabine and myeloablative alkylating-agent doses were designed to allow safer administration of dose-intensive therapy. Conditioning dose-intensity is highly correlated with outcome after SCT. Increased dose-intensity is associated with reduced relapse risk, but also with higher non-relapse mortality. Overall outcome is determined by the net effect of these opposing effects as may be predicted by patient age, comorbidities and disease status at transplantation. Retrospective comparative trials showed that while outcome may be similar with the various regimens in patients given SCT in remission, NMA/RIC are inferior when SCT is given in advanced disease, due to high relapse risk. RTC regimens may be more effective in this setting yet better tolerated by patients not eligible for myeloablative conditioning. Randomized studies are needed to define the role of different regimens. Future studies will also focus on the design of more accurate models to select the best regimen in each setting. A search for novel regimens or post-transplant approaches with more intensive anti-leukemic activity, but limited toxicity will also be of marked benefit.