Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1–6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35–0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32–0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.
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We thank all the physicians and data managers at the transplant centers who contributed data to the Japan Society for Hematopoietic Cell Transplantation, the Japan Marrow Donor Program, the Japan Cord Blood Bank Network, and the Japanese Society of Pediatric Hematology/Oncology.
Inherited Disease Working Group of the Japan Society for Hematopoietic Cell Transplantation
Katsutsugu Umeda, Hiromasa Yabe, Koji Kato, Kohsuke Imai, Nao Yoshida, Yoji Sasahara, Souichi Adachi, Tomohiro Morio.
Conflict of interest
The authors declare that they have no conflict of interest.
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Umeda, K., Yabe, H., Kato, K. et al. Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning. Bone Marrow Transplant 54, 1227–1236 (2019) doi:10.1038/s41409-018-0418-8