Optimization of allogeneic transplant conditioning: not the time for dogma

Numerous reduced-intensity conditioning regimens for allogeneic hematopoietic cell transplantation are currently being explored, primarily in older patients and in individuals with comorbid conditions who are not eligible for conventional myeloablative conditioning regimens. There is agreement that these approaches have reduced early transplant-related (non-relapse) toxicity and mortality. It is unclear, however, whether these strategies improve long-term survival. Furthermore, as most trials with reduced-intensity regimens have enrolled older patients and patients with comorbid conditions, it is not appropriate to compare the results of these trials to those obtained with more conventional approaches. It remains to be determined whether younger patients, and patients without comorbid conditions, will derive significant long-term benefits from reduced-intensity regimens when compared to conventional strategies. It may be that the different approaches are complementary and in the end will preferentially serve specific patient populations based on age, comorbid conditions and malignancy type. To determine the role of reduced-intensity approaches, controlled prospective trials are needed, with enrolled patients being stratified according to comorbid conditions, disease characteristics, pre-transplant therapy and source of stem cells, at a minimum.