Our prior study using a less-intense conditioning regimen of fludarabine and melphalan 100 mg/m2 for allogeneic hematopoietic cell transplantation (HCT) showed promising results in lymphoma (Clin Lympphoma Myeloma Leuk 2015;15:655). In this retrospective study, we evaluated a Flu/Mel 100 conditioning regimen followed by allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH).


A total of 16 patients with HLH were included: six were enrolled in a prospective clinical trial (NCT00772811) and additional ten used the same conditioning regimen of fludarabine (30 mg/m2/day on days -6 to -2) and melphalan (100 mg/m2 on day -2). Antithymocyte globulin was added for unrelated or mismatched familial donor HCT.


Median age was 42 years (range, 18-64), and 12 patients had EBV-associated HLH. The hematopoietic cell donor was an HLA matched sibling for nine patients, an unrelated matched volunteer for five, and a mismatched family member for two. Median time from diagnosis to allogeneic HCT was 2.7 months. Except three patients who died early after HCT, 13 patients achieved an absolute neutrophil count > 500/μL on median day 12, and 12 achieved transfusion-independent platelet counts > 20,000/μL on median day 16. Five patients experienced acute graft-versus-host disease (GVHD): grade II in one and grade III/IV in four. Chronic GVHD occurred in three patients: moderate in one and severe in two. After a median follow-up of 33.8 months, one progressed, three relapsed, and nine died. Five deaths were not related to relapse or progression: infection (n=3), bleeding (n=1), and GVHD (n=1). No deaths or relapses were observed after 124 days post-transplant. Overall survival probability was 48.6%, and it was significantly different according to pre-transplant ferritin level (P=0.007) and cytopenia (P=0.021). Before allogeneic HCT, EBV-DNA was still positive in 10 of 12 EBV-associated HLH patients: six patients showed negative conversion of EBV-DNA after HCT, two showed persistent EBV-DNA, and two were not assessable due to early death.


Conditioning therapy with a lower dose of melphalan, combined with fludarabine, appears to be promising in allogeneic HCT for HLH. Strategies to prevent early death seem to be needed.


Park: Boehringer Ingelheim: Research Funding. Lee: Boehringer Ingelheim: Research Funding. Ko: Boehringer Ingelheim: Research Funding. Lee: Boehringer Ingelheim: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.