Non-myeloablative matched sibling stem cell transplantation with the optional reinforced stem cell infusion for patients with hemoglobinopathies.
BACKGROUND
The NIH protocol for non-myeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low-dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft-versus-host disease. However, alloSCT using NMA conditioning had been rarely applied to β-thalassemia major (β-TM) patients.


METHODS
To avoid prolonged immunosuppression, we developed a two-stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH protocol. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immunosuppression or experiencing impending graft failure.


RESULTS
In this study, β-TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four β-TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion achieved complete (n = 4) or mixed chimerism (n = 1). The overall survival rate and event-free survival at 4 years were 91.7% (95% CI; 53.9-98.8) in both groups, with a thalassemia-free survival rate in β-TM patients of 87.5% (95% CI; 38.7-98.1).


CONCLUSION
This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult β-TM patients.
['Shin|Seung-Hwan|SH|https://orcid.org/0000-0002-8472-7041', 'Park|Sung-Soo|SS|', 'Park|Silvia|S|https://orcid.org/0000-0003-2845-2933', 'Jeon|Young-Woo|YW|', 'Yoon|Jae-Ho|JH|https://orcid.org/0000-0002-2145-9131', 'Yahng|Seung-Ah|SA|https://orcid.org/0000-0002-3044-3991', 'Cho|Byung-Sik|BS|', 'Kim|Yoo-Jin|YJ|', 'Lee|Seok|S|', 'Kim|Hee-Je|HJ|', 'Min|Chang-Ki|CK|', 'Cho|Seok-Goo|SG|', 'Kim|Dong-Wook|DW|', 'Lee|Jong-Wook|JW|', 'Eom|Ki-Seong|KS|']
D018380:Hematopoietic Stem Cell Transplantation D006453:Hemoglobinopathies D006801:Humans D011379:Prognosis D035781:Siblings D018183:Transplantation Chimera D019172:Transplantation Conditioning D014184:Transplantation, Homologous D016896:Treatment Outcome D017086:beta-Thalassemia
sickle cell disease β-thalassemia major non-myeloablative conditioning