Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP)

BACKGROUND: Hemophagocytic lymphohistiocytosis is a life-threatening disease. Hematopoietic stem cell transplantation still represents the treatment of choice for most patients with this disease. DESIGN AND METHODS: We retrospectively analyzed 61 patients with hemophagocytic lymphohistiocytosis who underwent HSCT over a 17-year period at nine centers affiliated to the Italian Pediatric Hematology Oncology Association (AIEOP). The median time from diagnosis to hematopoietic stem cell transplantation was 0.6 years (range, 0.13-5). The donor for the first hematopoietic stem cell transplantation was either a relative (43%) or an unrelated volunteer (57%). Fifty-four patients (89%) had a complete genetic study, which led to the diagnoses of FHL2, due to perforin defect (21 patients), FHL3, due to Munc 13-4 defect (14 patients), Griscelli disease (2 patients), X-linked lymphoproliferative disease (1 patient), and CATCH22 syndrome (1 patient). No mutations were found in the remaining 15 patients. Twenty-one patients had neurological involvement at diagnosis. RESULTS: Three patients failed to engraft. Grade II-IV acute and chronic graft-versus-host disease occurred in 31% and 17% of patients, respectively. Overall, 39 patients are alive (64%), 15 died of toxicity, 6 of progressive disease and 1 of sudden death. The 8-year overall survival probability was 58.6% (95% confidence interval, 42-72), while the cumulative incidence of transplantation-related mortality was 25.7% (95% confidence interval, 16-40). The outcome of patients with a known genetic defect was comparable to that of patients without mutation. Neurological sequelae were reported in seven patients, six of whom had central nervous system disease at diagnosis. CONCLUSIONS: These data confirm that hematopoietic stem cell transplantation represents a curative treatment for a large proportion of patients with hemophagocytic lymphohistiocytosis, irrespective of the underlying genetic defect.