Original Article
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Blood Res 2018; 53(2):
Published online June 25, 2018
https://doi.org/10.5045/br.2018.53.2.145
© The Korean Society of Hematology
Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin
1Department of Pediatrics, Catholic Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
Correspondence to : Nack-Gyun Chung, M.D., Ph.D. Department of Pediatrics, Catholic Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. cngped@catholic.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords Hematopoietic stem cell transplantation, Myeloablative conditioning, Sickle cell disease, Thalassemia major
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Original Article
Blood Res 2018; 53(2): 145-151
Published online June 25, 2018 https://doi.org/10.5045/br.2018.53.2.145
Copyright © The Korean Society of Hematology.
Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin
Bo-Kyoung Park1, Hyo-Sup Kim1, Seongkoo Kim1, Jae-Wook Lee1, Young Shil Park2, Pil-Sang Jang1, Nack-Gyun Chung1*, Dae-Chul Jeong1, and Bin Cho1
1Department of Pediatrics, Catholic Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
Correspondence to:Nack-Gyun Chung, M.D., Ph.D. Department of Pediatrics, Catholic Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. cngped@catholic.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Hematopoietic stem cell transplantation, Myeloablative conditioning, Sickle cell disease, Thalassemia major
Fig 1.
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Abbreviations: SCD, sickle cell disease; TM, thalassemia major.
Fig 2.
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Abbreviations: SCD, sickle cell disease; TM, thalassemia major.
Fig 3.
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Table 1 .
Patient characteristics. .Abbreviations: HSCT, hematopoietic stem cell transplantation; SCD, sickle cell disease; TM, thalassemia major..
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Table 2 .
Transplantation characteristics. .a)HLA-A, -B, -C, -DR matching with DNA typing. b)With the exception of one haploidentical transplantation HSCT, conditioning was performed with total body irradiation, busulfan, fludarabine and ATG..
Abbreviations: ATG, anti-thymocyte globulin; BM, bone marrow; GVHD, graft-versus-host disease; HLA, human leukocyte antigen; PBSC, peripheral blood stem cell; SCD, sickle cell disease; TM, thalassemia major..
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Table 3 .
Transplantation outcomes. .a)Days after stem cell transplantation..
Abbreviations: CMV, cytomegalovirus; EBV, Epstein-Barr virus; GVHD, graft-versus-host disease; SCD, sickle cell disease; TM, thalassemia major..
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