The Effectiveness of Once-Daily Intravenous Busulfan as Conditioning for Hematopoietic Stem Cell Transplantation in Children with Acute Myelogenous Leukemia.
Authors: Park Seong Shik , Kim Seong Heon , Lim Young Tak 
Published: October 2019

Abstract
High-dose busulfan (Bu) is a frequent component of cytotoxic preparative regimens for hematopoietic stem cell transplantation (HSCT). An intravenous (IV) Bu has been used with the traditional 4 times daily dosing because of high compliance, predictable bioavailability and reduced toxicities compared with oral Bu. Recently, there have been some reports suggesting that once-daily IV Bu possibly reduces toxicities without influencing clinical outcome compared with the 4 times daily dosage schedule. We report the clinical outcome of once-daily IV Bu as conditioning regimens of HSCT in children with acute myelogenous leukemia (AML) at single center in Korea. Nine AML children who received HSCT using the conditioning regimen which containing once-daily IV Bu at department of Pediatrics, Pusan National University Hospital from March 2003 to July 2007 were analyzed retrospectively. IV Bu was administered on 4 consecutive days in once-daily schedule of 110–130 mg/m2 and lorazepam was also given together. We analyzed a engraftment status, transplant-related toxicities, GVHD and relapse after HSCT.
FAB classification of nine AML patients were M1 (n=3), M2 (n=4) and M4Eo (n=1). Male were seven and female were two. The mean age at diagnosis and at HSCT were 9.14 and 9.94 years. Eight patients were in first complete remission (CR) and one patient was in second CR at the time of HSCT. HLA matched sibling peripheral HSCT were four, HLA matched unrelated bone marrow transplantation (BMT) were two, related cord blood transplantation (CBT) was one, unrelated CBT was one and autologous HSCT was one. As for conditioning regimens, HLA matched sibling peripheral HSCT (n=4) were Flu (fludarabine)/Bu, CBT and unrelated BMT (n=4) were Flu/Bu/ATG (antithymocyte globulin) and autologous HSCT (n=1) was Bu/Cy (cyclophosphamide). The average dose of infused nucleated cells and CD34+ cells except CBT were 7.7x108/kg and 5.9x106/kg. There was only one case of primary graft failure in unrelated donor CBT recipient. The median time to neutrophil engraftment was 14 days (range, 12–19 days) and platelet engraftment 19 days (range, 13–33 days). Transplant-related toxicities were acceptable; there was no case with CNS toxicity, grade 3–4 mucositis occurred in seven patients and grade 2–3 hepatotoxicity in all, but transient. Veno-occlusive disease (VOD) was observed in two cases; 1 mild VOD and 1 moderate VOD. Acute GVHD was noted in two cases; grade 1 and grade 4. With a median follow up of 21 months, there were two cases of relapse of leukemia after HSCT and two cases of death; one developed disease progression after relapse and another one resulted from grade 4 acute GVHD. Once-daily IV Bu as conditioning regimens of HSCT in children with AML was well tolerated, convenient with relatively moderate toxicities, but additional studies are needed to determine the therapeutic efficacy and pharmacokinetics of once-daily IV Bu in children undergoing HSCT.