Comparison of Two Busulphan-Based Conditioning Regimens Outcomes for Children and Young Adults with Acute Myeloid Leukemia in a Silgle Center in Brazil

Introduction: As well as best allogeneic donor choice is imperative to bone marrow transplant (BMT), best conditioning regimen is one of the major cornerstones of the treatment success. Although high-dose busulfan have been employed along with cyclophoshamide (BuCy) for more than two decades as one of the best options for allogeneic BMT in acute myeloid leukemia patients (AML), we were unable to attain the best published outcomes in our center, which led us to pursue new treatment strategies, including alternative conditioning regimens. We chose to use a combination of Busulfan and Melphalan (BuMel) together with Busulfan plasma concentration monitoring.

Objective: to compare outcomes of children and young adults who underwent allogeneic BMT for AML using two different myeloablative conditioning regimens without radiotherapy.

Methods: retrospective analysis of data.

Results: from September, 1999, to July, 2016, 40 patients (30 male), median age 4,6 yo (1,2 to 20,7) underwent allogeneic BMT at Instituto de Oncologia Pediatrica (GRAACC - IOP - UNIFESP). Third-four patients had matched related donors. Median follow-up was 472 days. BuCy (oral busulfan 16 mg/kg or intravenous equivalente dose and cyclophosphamide 200 mg/kg) was the conditioning regimen for 15 patients, and BuMel (oral busulfan 16 mg/kg or intravenous equivalent dose and melphalan 140 mg/m2) for the other 25. Graft versus host disease (GVHD) prophylaxis included rabbit antithymocyte globulin for six matched unrelated transplants. Half of the patients were in first, 19 in second and one in third remission. Bone marrow stem cells were used in the majority of the procedures (38). Only two out of 15 patients who received BuCy as conditioning regimen are alive (OS 13%), versus 15 of the 25 who were transplanted using BuMel (OS 60%). Leukemia relapse was cause of death in 70% for BuCy, followed by transplant-related mortality (TRM) in 23% and GVHD in 7% of the cases. In BuMel group, main cause of death was GVHD (50%), followed by leukemia relapse (20%), TRM (20%) and one disseminated fusariosis. Busulphan pharmacokinetics was available for 18 procedures (17 BuMel and one BuCy). Death rate for those patients was 44%, against 68% for those who had not their busulphan plasmatic levels monitored. However, BuCy was the chosen conditioning regimen for 14 of the 22 patients in the latter group.

Conclusion: in view of the unsatisfactory results obtained with BuCy for allogeneic BMT in AML patients in our center urgent measures were required. The choice of a different conditioning regimen as well as busulphan pharmacokinetics monitoring from May, 2012 on, have led us to attain overall survival rates comparable to Center for International Blood and Marrow Transplant Research (CIBMTR) data. Longer follow up will be required to confirm our current data