Improved survival with bufulfan-cyclophosphamide combination vs total body irradiation

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1. IV busulfan combined with cyclophosphamide (BuCy) is associated with better leukemia-free and overall survival in acute myeloid leukemia (AML) than total body irradiation (TBI).

2. Improved outcomes and greater ease of administration favor BuCy over Cy/TBI for AML patients in first complete remission (CR) undergoing hematopoietic cell transplantation (HCT).

Evidence Rating Level: 2 (Good)

Study Rundown: The most common myeloablative conditioning regimens for allotransplant in AML patients include cyclophosphamide combined with TBI (Cy/TBI) or busulfan (BuCy). However, there are few comparisons of the outcomes of patients receiving these treatments, particularly in light of recent improvements in busulfan administration. Therefore, the goal of this study was to examine the long-term outcomes between these different treatment approaches. The authors found that IV Bu had significantly better outcomes in terms of leukemia free and overall survival. Given the reduced technical requirements of Bu administration compared to TBI, this supports further investigation into the uses of Bu in lieu of the traditional Cy/TBI therapy for this particular patient population. These results benefit from the large number of patients enrolled and the involvement of multiple institutions. However, it should be noted that this was a retrospective study, and patients were not randomly assigned to specific conditioning regimes. Though multivariate analysis corrected for demographic differences between the two treatment groups, several patient characteristics did vary such as age and year of transplantation. There was also variation in the dose of TBI, Bu and Cy. Therefore, future prospective studies into these treatment options may be necessary.

Click to read the study in Blood

Relevant Reading: One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

In-Depth [retrospective cohort study]: The authors of this study conducted a large, retrospective review of patients from over 500 transplant centers who had undergone first allogeneic HCT with HLA-identical siblings or unrelated donors between 2000 and 2006 for AML in first remission. They examined a total of 1230 patients who had undergone Cy/TBI or BuCy without additional agents, with a median follow-up of surviving patients of 5 years. The primary outcome measured was survival. Other information collected included relapse as defined by hematologic criteria, time to neutrophil and platelet recovery and graft-versus-host disease. The estimated leukemia-free survival and overall survival at 5 years was 41% (95% CI: 37-46%) and 43% (95% CI: 39-47%) for the TBI group, 54% (95% CI: 49-60%)and 61% (95% CI: 56-66%) for oral Bu and 57% (95%CI: 50-64%) and 58% (95% CI: 51-65%) for IV Bu (P < 0.001 for each).

By Monica Parks and Andrew Bishara

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