Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin.
- Author:
Bo Kyoung PARK
1
;
Hyo Sup KIM
;
Seongkoo KIM
;
Jae Wook LEE
;
Young Shil PARK
;
Pil Sang JANG
;
Nack Gyun CHUNG
;
Dae Chul JEONG
;
Bin CHO
Author Information
- Publication Type:Original Article
- Keywords: Hematopoietic stem cell transplantation; Myeloablative conditioning; Sickle cell disease; Thalassemia major
- MeSH: Anemia, Sickle Cell; Antilymphocyte Serum*; beta-Thalassemia; Bone Marrow; Bronchiolitis Obliterans; Busulfan; Child; Chimerism; Cyclophosphamide; Cyclosporine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation*; Hematopoietic Stem Cells*; Hemoglobinopathies*; Herpesvirus 4, Human; Humans; Incidence; Methotrexate; Mortality; Siblings; Stem Cells; Tissue Donors; Transplants
- From:Blood Research 2018;53(2):145-151
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for β-thalassemia major (TM) and sickle cell disease (SCD) in children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain significant challenges to improving survival after HSCT. Here, we analyzed the outcome of TM and SCD patients, who received allogeneic HSCT with myeloablative conditioning at our institution. METHODS: Twenty-two patients (15 TM, 7 SCD), with a median age of 9 years (range, 1.6–16.9), underwent allogeneic HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based conditioning. Cells were derived from either the bone marrow (8 patients), or peripheral blood stem cells (14 patients). The majority of patients received HSCT from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and short course methotrexate. RESULTS: All patients achieved donor engraftment. Two SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in 8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disease (PTLD) occurred in 1 patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all patients achieving transfusion independence, while 8 achieved complete donor chimerism. CONCLUSION: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD.
