Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide for Rescuing Patients With Graft Failure

Prognosis of patients with graft failure is dismal, and re-transplantation is the sole option for long-term survival. Currently, there is no consensus concerning therapeutic options in patients with primary or secondary (within the 60 days post-transplantation) graft failure and finding a new donor within an acceptable delay is challenging. Literature is poor on the subject while the overall survival of such patients is about 30% at 1 year. This situation thus represents today a very challenging unmet medical need.

Recently, haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy, which targets alloreactive T cells generated early after an HLA-mismatched transplant, sparing regulatory T cells and leaving unaffected the non-dividing hematopoietic stem cells) and standard post-transplant immune suppression with a calcineurin inhibitor (CNI) and mycophenolate mofetil. Our group re-transplanted a patient who experienced two consecutive graft failures and was successfully managed through a third haplo-SCT from her son using PTCy. We then retrospectively collected and analyzed data from 26 primary graft failure patients transplanted between 2011 and 2017 in 15 centers on behalf of French Society for Stem Cell Transplantation and Cell Therapy (SFGM-TC). The study population consisted mainly of patients with primary or secondary (within the 60 days post-transplantation) graft failure who underwent haplo-SCT and received PTCy as graft-versus-host-disease prophylaxis. The 1-year overall survival was about 60% suggesting that this approach might be a valid option in this particular poor clinical situation but now need validation through a phase II multicenter, national, prospective cohort study.