Blood Res.  2018 Jun;53(2):145-151. 10.5045/br.2018.53.2.145.

Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin

• Park BK
• Kim HS
• Kim S
• Lee JW
• Park YS
• Jang PS
• Chung NG
• Jeong DC
• Cho B

• KMID: 2451033
• DOI: http://doi.org/10.5045/br.2018.53.2.145

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.

Keyword

Hematopoietic stem cell transplantation; Myeloablative conditioning; Sickle cell disease; Thalassemia major

MeSH Terms

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
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Cyclosporine
Methotrexate

Figure

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  Fig. 1 Cumulative incidence of grade ≥2 acute graft-versus-host disease (aGVHD).Abbreviations: SCD, sickle cell disease; TM, thalassemia major.

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  Fig. 2 Cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD).Abbreviations: SCD, sickle cell disease; TM, thalassemia major.

• 

  Fig. 3 Overall survival of thalassemia major (TM) and sickle cell disease (SCD) after allogeneic hematopoietic stem cell transplantation.

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