A NOVEL conditioning regimen for haematopoietic stem cell transplantation in sickle cell disease demonstrates high survival, robust donor engraftment, and low graft versus host disease rates in adolescents and adults.
Conditioning Regimen and Transplant Outcomes
Myeloablative human leukocyte antigen matched related donor haematopoietic stem cell transplantation is a potentially curative treatment for individuals with sickle cell disease, with survival rates exceeding 90%. However, the optimal conditioning strategy for older patients remains uncertain.
In this prospective multicentre study, investigators evaluated a novel regimen comprising thymoglobulin, thiotepa, cyclophosphamide, fludarabine, and low dose total body irradiation. The aim was to improve donor engraftment, reduce graft versus host disease, and minimise treatment related toxicity.
A total of 25 patients were recruited across three centres, with the majority receiving fully matched sibling transplants (88%). A small proportion underwent transplantation from a one antigen mismatched sibling donor, and 12% had previously experienced a second graft failure following earlier transplantation. Stem cell sources included both bone marrow and peripheral blood, reflecting current clinical practice. The median age of participants was 26.7 years, with a median follow up of 42 months.
Engraftment and Survival Outcomes
The findings demonstrated strong efficacy, with an estimated 5-year event free survival rate of 96% and a 2-year overall survival rate of 100%. Notably, no graft failure was observed. Donor engraftment was robust, with median whole blood chimerism reaching 100% at day 28 and remaining high at 97% at one year. Among evaluable participants, 81% were able to discontinue immunosuppression one year after transplantation, indicating sustained graft function and immune tolerance.
Safety and Clinical Implications
The safety profile of the regimen was favourable. The one-year incidence of grade III to IV acute graft versus host disease was 4%, with only one reported case, and no chronic graft versus host disease was observed. These findings suggest that the conditioning approach effectively reduces the risk of severe immune complications while maintaining high engraftment rates.
Importantly, optimal donor engraftment is associated with a lower risk of secondary myeloid neoplasms, highlighting the broader clinical relevance of achieving stable chimerism. This study supports the use of an intensified yet well tolerated conditioning strategy in adolescents and adults with severe sickle cell disease, including those undergoing repeat transplantation, and may inform future standards of care.
Reference
Alasbali R et al. Excellent outcomes using a novel reduced intensity conditioning with thiotepa and post-transplant cyclophosphamide for HLA-matched related donor transplant in adolescents and adults with sickle cell disease. Bone Marrow Transplant. 2026;https://doi.org/10.1038/s41409-026-02876-3.
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