Favorable Outcomes Following Allogeneic Transplantation in Adults with Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome marked by a severe hyperinflammatory state characterized by aberrant T-cell and NK cell activity leading to prolonged hypercytokinemia and can be rapidly fatal if not diagnosed and treated early. While upfront therapy is aimed at reducing hyperinflammation and controlling possible triggers, allogeneic hematopoietic stem-cell transplantation (HSCT) is indicated for primary and relapsed/refractory cases to attain sustained remission. While this has been explored extensively in the pediatric population, there are limited data on adults undergoing HSCT for HLH. We analyzed transplant outcomes in an adult HLH population in the modern era who were transplanted at Dana-Farber Cancer Institute from 2010 onwards. Patients were uniformly transplanted on a reduced intensity platform incorporating early administration of alemtuzumab with standard infectious and graft-versus host disease prophylaxis. Engraftment was documenyed for all patients. At 3 years post-transplantation, overall survival (OS) was 75% (95% CI 51,89) while 3-year progression-free survival was 71% (95% CI 46,86). The 3-year cumulative incidence (CI) of relapse was 15% (95% CI 3.4,33). There were no isolated HLH relapses without relapse of malignancy. CI of non-relapse mortality at 3 years was 15% (95% CI 3.5,34). Infectious complications and GVHD outcomes were comparable to standard RIC transplantation at our institute. Mixed chimerism was common but did not correlate with transplant outcomes. Our data suggests that the immune defect in HLH can be abrogated with allogeneic transplantation using a reduced intensity regimen with early administration of alemtuzumab as pre-conditioning, providing a potentially curative option for this difficult disease.