T-cell depleted haploidentical hematopoietic stem cell transplantation is the optimal graft source for patients with familial hemophagocytic lymphohistiocytosis who do not have matched family donors.

Abstract

Familial hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune regulation. When managed appropriately with systemic chemotherapy, cure can be achieved by subsequent allogeneic hematopoietic stem cell transplantation (HSCT). Although the best results are obtained with matched-family donors (MFD), alternative donor transplants may be necessary when such donors are not available. As there is urgency to proceed with curative therapy, T-cell depleted haploidentical HSCT could be a viable option as a parent or other haploidentical family member would be available instantly. Between August 2010 and September 2015 we performed haploidentical HSCT for six patients with HLH in this institution. These patients did not have MFDs, and in our center it was logistically easier to perform an haploidentical HSCT rather than to pursue with an unrelated donor or cord blood search from the international registries. The median age at transplant was 6 months (5–31 months) and all had perforin gene mutations. The first two patients had CD3/CD19 depleted procedures while the rest underwent TCR alpha/beta and CD19 depletion for faster immune reconstitution. All six patients engrafted following the transplant with minimal graft versus hot disease. Four patients are cured from the disease with a median follow-up of 3 years (7mths to 5 years). Two patients (siblings) who were transplanted in partial remission expired 2 months following transplant from multi-organ failure after successful engraftment. In the presence of an appropriate transplant laboratory facility, T-cell depleted haploidentical HSCT should be considered as the graft of choice for patients with HLH who do not have HLA-matched family donors.