Transplantation in Adult Patients with Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis: Yes or No?

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by aberrant immunological activity with a dismal prognosis. Epstein-Barr virus-associated HLH (EBV-HLH) is the most common type among adults. Patients with EBV infection to B cells could benefit from rituximab, whereas lethal outcomes may occur in patients with EBV infection to T cells, nature killer (NK) cells, or multilineages. The necessity of allogeneic hematopoietic stem cell transplantation (HSCT) in adult EBV-HLH patients remains controversial. A total of 356 adult EBV-HLH patients entered this study. Eighty-eight received HSCT under medical recommendation. Four received salvage HSCT. The 5-year overall survival (OS) rate of HSCT group was 48.7% (vs 16.2% in non-transplanted patients, p<0.001). There was no difference in OS between patients who received transplantation at first complete remission (CR1) and those at first partial remission (PR1) nor between patients at CR1 and CR2. Patients who received transplantation at PR2 had inferior survival. The rate of reaching CR2 was significantly higher in patients with CR1 than PR1 (p=0.014). Higher sCD25 levels, higher EBV-DNA loads in plasma after HSCT, poorer remission status, more advanced acute graft-versus-host disease (aGVHD), and the absence of localized chronic GVHD (cGVHD) were associated with an inferior prognosis (p<0.05). HSCT improved the survival of adult EBV-HLH significantly. For patients who achieved PR after initial treatment, HSCT was recommended. A wait-and-see strategy could be adopted for patients who achieved CR after initial treatment, but with the risk of failing to achieve a second CR.