Outcome of Hematopoietic Cell Transplant for Hemophagocytic Lymphohistiocytosis in Adults: A Single Center Experience

Background: Hemophagocytic lymphohistiocytosis (HLH), a group of immunodeficiency disorder characterized by defective lymphocyte cytotoxicity and immune dysregulation leading to hyper inflammatory state. If untreated, this condition is potentially fatal. Currently, allogeneic hematopoietic cell transplantation (HCT) is the only definitive curative therapy for HLH. Recently, with increased awareness, HLH is being diagnosed in adults. However, there is very limited data on HCT outcome for adults with HLH. Here we report our experience of allogeneic HCT for HLH in adults (≥18 years). 

Methods:  We retrospectively analyzed the outcomes of 10 adult patients with HLH (7 male and 3 female) who had undergone allogeneic HCT between January 2004 and September 2012 in our institution. Genetic diagnosis was made in 4 patients (2 perforin defect, one MUNC 13-4, one XIAP). CNS involvement at diagnosis was noted in 5 patients, all of them received some form of induction therapy based on HLH-2004 protocol, and at the time of transplant HLH was well controlled in seven patients. The median age at transplantation was 20.2 years (range: 18.1-27.2). Majority (9/10) underwent reduced-intensity conditioning (RIC) regimen consisting of alemtuzumab, fludarabine, and melphalan. One underwent myeloablative preparative regimen consisting of busulfan, cyclophosphamide, and ATG. Nine patients received transplants from HLA- matched donors (8-MUD and 1 MSD). Bone marrow was the source of stem cell in seven patients and PBSC in another three. In most patients (9/10) cyclosporine and prednisone was used as GvHD prophylaxis.

Result: Overall survival was 50% (5/10) at a median follow-up of 17 months post-transplant (range: 6 -82). In patients who received RIC the survival was 56% (5/9).  The median time for neutrophil engraftment was 11 days (range: 9-15). Grade II to IV acute GvHD developed in two patients. Mixed donor chimerism was noted in 33% (3/9) of patients who received RIC. Of the five patients who died one died prior to engraftment on day 9, and other on day 45, three other died after day+ 100( range: 193 -324). The cause of death was bacterial sepsis with multi-organ failure in three patients, and acute gut GvHD with intestinal perforation and candidemia in one, and progressive necrotizing leukoencephalopathy in another. Of the surviving five patients, NK cell function had normalized in all of them and none have developed chronic GvHD.

Conclusion: Overall survival of 56% with RIC in young adults with HLH is lower than the 88% survival reported  in patients less than 18 years of age from our center (p<.05). Prospective multicenter study is warranted to validate the present finding, and also better identify the risk factors in adults to improve HCT outcome for HLH.