title: Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies Using a Tailored Busulfan-Based Conditioning Regimen: Single-Center Experience.
abstract: Hematopoietic stem cell transplantation (HSCT) is the only proven curative option for patients with hemoglobinopathies, both thalassemia and sickle cell anemia (SCA). A busulfan-based myeloablative conditioning regimen is the standard of care for HSCT in these patients, although increased treatment-related morbidity, including veno-occlusive disease (VOD), has been demonstrated. Thirty-eight pediatric patients, median age 8 years (range, 6 months to 22 years), suffering from hemoglobinopathy were treated at Rambam Medical Center in Haifa, Israel, between 1998 and 2011. Thirty-four patients had thalassemia major and 4 had SCA. The 38 patients underwent 40 HSCTs, 34 of which were first transplants and 6 second transplants. Most transplants (32/40) were from matched sibling donors. Sources of stem cells were peripheral blood in 30 transplants, bone marrow in 7 transplants, and cord blood in 3 transplants. All received different customized busulfan-based conditioning regimens tailored by pharmacokinetic analysis of busulfan levels. Primary engraftment occurred in 37 of 40 transplants. Neutrophil engraftment (>.5 × 10(9)/L) occurred at a median of 15.3 days post-transplantation (range, 10 to 45). Platelet transfusion independence (>20 × 10(9)/L) occurred at a median of 22.3 days (range, 11 to 60). The rate of 5-year overall survival for thalassemia patients after first transplantation was 90.5% ± 5.3%. The rate of 5-year thalassemia-free survival was 81.7% ± 6.8%. Cumulative incidence of acute graft-versus-host disease (GVHD) was 17.6%. Rate of grades III to IV GVHD was 8.8%. Cumulative incidence of chronic GVHD was 23.5%, with 11.8% incidence of extensive chronic GVHD. One patient developed VOD. Full donor chimerism occurred in 36.4% of patients with class 1 + 2 thalassemia, compared with 78.6% in class 3 thalassemia (P = .049). Overall survival above 90% in patients undergoing their first transplant was demonstrated using busulfan-based conditioning regimens. The low incidence of VOD was probably due to busulfan area under the curve measurements and dose adjustment.
authors.affiliation: Department of Pediatric Hematology Oncology, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Zaidman
authors.affiliation: Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.affiliation: Department of Pediatric Hematology Oncology, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Abdalla
authors.initials: A
authors.lastname: Khalil
authors.affiliation: Department of Pediatric Hematology Oncology, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ben-Arush
authors.affiliation: Department of Pediatric Hemato-Oncology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel. Electronic address: ronite@tasmc.health.gov.il.
authors.forename: Ronit
authors.initials: R
authors.lastname: Elhasid
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000401:mortality / Q000628:therapy; D002066:Busulfan / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006453:Hemoglobinopathies / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007223:Infant; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology; D055815:Young Adult; D017086:beta-Thalassemia / Q000401:mortality / Q000628:therapy
chemical_list: D002066:Busulfan
keywords: Busulfan; Chimerism; Stem cell transplantation; Thalassemia major; VOD