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

Haematologica. 2008 Nov;93(11):1694-701. doi: 10.3324/haematol.13142. Epub 2008 Sep 2.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Graft vs Host Disease / epidemiology
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Infant, Newborn
  • Italy
  • Lymphohistiocytosis, Hemophagocytic / surgery*
  • Retrospective Studies
  • Survival Analysis
  • Survivors

Substances

  • Antineoplastic Agents