Acute myeloid leukemia is the most common indication for an allogeneic hematopoietic cell transplant. The introduction of reduced intensity conditioning has expanded the recipient pool for transplantation, which has importantly made transplant an option for the more commonly affected older age groups. Reduced intensity conditioning allogeneic transplantation is currently the standard of care for patients with intermediate or high-risk acute myeloid leukemia and is now most often employed in older patients and those with medical comorbidities. Despite being curative for a significant proportion of patients, post-transplant relapse remains a challenge in the reduced intensity conditioning setting. Herein we discuss the studies that demonstrate the feasibility of reduced intensity conditioning allogeneic transplants, compare the outcomes of reduced intensity conditioning versus chemotherapy and conventional myeloablative conditioning regimens, describe the optimal donor and stem cell source, and consider the impact of post-remission consolidation, comorbidities, center experience, and more intensive (reduced toxicity conditioning) regimens on outcomes. Additionally, we discuss the need for further prospective studies to optimize transplant outcomes.
ABSTRACTas the backbone of most RIC regimens which also include either a reduced dose of an alkylating agent or a reduced dose of TBI. Fludarabine is generally well tolerated and synergizes well with alkylating agents to enhance inhibition of DNA repair mechanisms. 10 Multiple RIC regimens have been developed and described [12][13][14][15][16][17][18][19] (Table 1).In the late 1990s and early 2000s, the feasibility and efficacy of lower intensity conditioning regimens were demonstrated in several studies that showed successful engraftment in recipients of grafts from both related 19,20 and unrelated donors. 21,22 These regimens were also demonstrated to be a treatment modality that can be successful in older patients with hematologic malignancies. 23 McSweeney et al. described 45 patients with a median age of 56 years who had human leukocyte antigen (HLA)-identical sibling donors and relative contraindications to conventional conditioning for HCT. In these patients a conditioning regimen of TBI alone (200 cGy) produced a survival rate of >66% after a median follow-up of 417 days with a NRM rate of only 6.7%. The associated toxicities were mild, and over 50% of patients were able to have their transplant done completely in the outpatient setting. 23 This set the stage for future studies focusing on the potent immunological graft-versus-leukemia effect to induce cures as opposed to just on intensive pre-transplantation marrow ablative strategies.As the number of efficacious regimens grew, so did the number of patients for whom transplantation became a therapeutic option. Much enthusiasm has led to the widespread adoption of RIC HCT as a potentially curative option for older patients or those with comorbid disease, despite lack of supportive, prospective, randomized d...
