Allogeneic Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide in Patients With Large Paroxysmal Nocturnal Hemoglobinuria Clones.

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for paroxysmal nocturnal hemoglobinuria (PNH). Post-transplant cyclophosphamide (PTCy) has improved HSCT safety in other diseases, but its use in PNH is poorly characterized.

METHODS

In this retrospective study, we analyzed outcomes of 19 patients with large PNH clones (≥ 50%) undergoing HSCT (2016-2025). Seven patients received a PTCy-based platform (fludarabine-busulfan-cyclophosphamide conditioning with PTCy-based graft-versus-host disease [GvHD] prophylaxis), whereas 12 received conventional prophylaxis.

RESULTS

Patients' median age was 32 years; 68% had PNH with bone marrow failure. After a median follow-up of 1349 days, overall and event-free survival rates were 100% and 94.4%, respectively. All patients engrafted rapidly with full donor chimerism. No cases of chronic or grades II-IV acute GvHD occurred in the PTCy group (0/7); however, chronic GvHD and grades II-IV acute GvHD occurred in 15.8% and 10.5% of patients in the conventional group, respectively. No transplant-related mortality or thrombotic events occurred.

CONCLUSION

This study, representing the largest reported experience with PTCy-based HSCT for PNH, suggests that this platform is feasible and associated with excellent survival and a promising GvHD profile. These preliminary findings support further investigation of PTCy in transplant strategies for PNH.