Allogeneic Hematopoietic Stem Cell Transplantation Using An Intravenous Busulfan Based Myeloablative Conditioning without Total Body Irradiation for Pediatric Patients with Acute Lymphoblastic Leukemia

Abstract 3547

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukaemia (ALL) has been most commonly performed using a myeloablative, total body irradiation (TBI)-based preparative regimen; however, there are emerging concerns about long-term sequelae of TBI in pediatric patients. The availability of intravenous (i.v.) busulfan (Bu) prompted us to evaluate the effectiveness of i.v. Bu-based preparative regimens on pediatric patients who underwent allo-SCT for ALL. We retrospectively evaluated the outcomes of 31 children with ALL transplanted with i.v. Bu-based preparative regimens at our institution between January 2005 and May 2010. Twenty-one patients were in first complete remission (CR1), 8 in CR2, 1 in CR3, and 1 in advanced disease. The donors were HLA-matched siblings (n=9), matched unrelated (n=20), or 1-antigen mismatched related donors (n=2). The median age of the patients was 4.8 years (range, 2 months-16.7 years). Twenty patients received bone marrow, 8 peripheral blood stem cells, and 3 cord blood. Busulfan was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16–23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Busulfan administration was followed by Cyclophosphamide and VP-16 in 21 patients, Cyclophosphamide and Thiotepa in 6, Cyclophosphamide and Melphalan in 2 and Cyclophosphamide and Fludarabine in 2 patients. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine A and Methotrexate in all patients transplanted with blood or marrow stem cells, while Methotrexate was omitted in those patients who underwent cord blood allo-HSCT. Anti-thymocyte globulin was added in patients transplanted from an unrelated donor. All patients but one achieved sustained engraftment. Median time to ANC>500, and platelets>20.000 was 19 days (range14-29), and 21.5 days (range 12–44) respectively. One patient died on day 10 and another patient relapsed on day 22; both were considered invaluable for engraftment. There were 6 cases of mild veno-occlusive disease, and 5 cases of hemorrhagic cystitis. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15/31 and 5/31 patients, respectively. At median follow-up of 27 months, 23 patients are alive and diseases free. Four patients died of relapse and 4 died of transplant-related mortality (TRM). The overall survival (OS) rate, relapse rate, and TRM rate were 67 %, 24%, and 10%, respectively. These results are comparable to those reported with TBI-based preparative regimens and suggest that it is time to re-evaluate the use of TBI in ALL patients.