An International Learning Collaborative Phase 2 Trial for Haploidentical Bone Marrow Transplant in Sickle Cell Disease
AUTHORS
- PMID: 38493482 [PubMed].
ABSTRACT
In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that non-myeloablative related haploidentical BMT with thiotepa and post-transplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants (median age 19.1 (IQR 14.1 – 25.0) were evaluable based on the conditioning protocol. Graft failure occurred in 11.4% (8/70) and only in participants <18 years (p=0.001); all had autologous reconstitution. After a median follow-up of 2.4 years (IQR 1.5-3.9), the 2-year Kaplan-Meier-based probability of event-free survival was 82.6% (95% CI 71.4%-89.7%). The 2-year overall survival was 94.1% (95% CI 84.9%-97.7%) with no difference between the child and adult participants (p=0.889). After excluding participants with graft failure (n=8), participants with engraftment had median whole blood donor chimerism values at D+180 and D+365 post-transplant of 100.0% (IQR 99.8 – 100.0%; n=59) and 100.0% (IQR 100.0 – 100.0%; n=58), respectively, and 96.6% (57/59) were off immunosuppression at 1-year post-transplant. The 1-year grades III-IV acute graft versus host disease (GvHD) rate was 10.0% (95% CI 4.6 – 18.6%), and the 2-year moderate-severe chronic GvHD rate was 10.0% (95% CI 4.6 – 18.6%). Five participants (7.1%) died from infectious complications. We demonstrate that non-myeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, instead of the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates (ClinicalTrials.gov identifier NCT01850108).
Tags: 2024 Alumni Publications