Allogeneic Hematopoietic Stem Cell Transplantation Using An Intravenous Busulfan Based Myeloablative Conditioning without Total Body Irradiation for Pediatric Patients with Acute Lymphoblastic Leukemia
Authors: Goussetis Eugene , Paisiou Anna , Peristeri Ioulia , Kitra Vassiliki , Vessalas George , Dimopoulou Maria N , Baltathakis Ioannis , Graphakos Stelios 
Published: October 2019

Abstract
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.

Disclosures:
No relevant conflicts of interest to declare.