Published online March 20, 2006
PEDIATRICS Vol. 117 No. 4 April 2006, pp. e743-e750 (doi:10.1542/peds.2005-1789)
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Hematopoietic Stem Cell Transplantation in Hemophagocytic Lymphohistiocytosis: A Single-Center Report of 48 Patients

Marie Ouachée-Chardin, MDa, Caroline Elie, MDb, Geneviève de Saint Basile, MD, PhDc,d, Françoise Le Deist, MD, PhDc,d, Nizar Mahlaoui, MDa, Capucine Picard, MD, PhDa, Bénédicte Neven, MDa, Jean-Laurent Casanova, MD, PhDa,e, Marc Tardieu, MDf, Marina Cavazzana-Calvo, MD, PhDc,g, Stéphane Blanche, MD, PhDa and Alain Fischer, MD, PhDa,c

a Department of Pediatric Immuno-Hematology, Necker-Enfants Malades Hospital, Paris, France
b Department of Biostatistics, Necker-Enfants Malades Hospital, Paris, France
c Inserm Unit 429, Necker-Enfants Malades Hospital, Paris, France; University René Descartes, Paris, France
d Laboratory of Immunodeficiencies, Necker-Enfants Malades Hospital, Paris, France
e Inserm Unit 550, Faculty of Medicine Necker, Paris, France
f Department of Pediatric Neurology, Kremlin Bicêtre Hospital, Paris, France
g Department of Biotherapy, Necker-Enfants Malades Hospital, Paris, France

OBJECTIVES. Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically determined disorder characterized by the early onset of fever, hepatosplenomegaly, central nervous system disease, thrombocytopenia, coagulation disorders, and hemophagocytosis. It is caused by genetic defects that impair T cell–mediated and natural cytotoxicity. Chemotherapy- or immunotherapy-based treatments can achieve remission. Hematopoietic stem cell transplantation (HSCT), however, is the only curative option, but optimal modalities and long-term outcome are not yet well known.

METHODS. We retrospectively analyzed the outcome of HSCT that was performed in 48 consecutive patients who had FHLH and were treated in a single center between 1982 and 2004.

RESULTS. The overall survival was 58.5% with a median follow-up of 5.8 years and extending to 20 years. A combination of active disease and haploidentical HSCT had a poor prognosis because in this situation, HLH disease is more frequently associated with graft failure. Twelve patients received 2 transplants because of graft failure (n = 7) or secondary graft loss that led to HLH relapse (n = 5). Transplant-related toxicity essentially consisted in veno-occlusive disease, which occurred in 28% of transplants and was associated with young age, haploidentical transplantation, and the use of antithymocyte globulin (ATG) in the conditioning regimen. A sustained remission was achieved in all patients with a donor chimerism ≥20% of leukocytes. Long-term sequelae were limited, because only 2 (7%) of 28 patients experienced a mild neurologic disorder.

CONCLUSIONS. This survey demonstrates the long-term efficacy of HSCT as a cure of FHLH. HSCT preserves quality of life. It shows that HSCT should be performed as early as a complete remission has been achieved. Additional studies are required to improve the procedure and reduce its toxic effects.

Key Words: hemophagocytic lymphohistiocytosis • allogeneic hematopoietic stem cell transplantation • chimerism • veno-occlusive disease

Abbreviations: HLH—hemophagocytosis lymphohistiocytosis • FHLH—familial HLH • CNS—central nervous system • ATG—antithymocyte globulins • HSCT—hematopoietic stem cell transplantation • CR—complete remission • URD—unrelated donor • PR—partial remission • AD—active disease • MSD—matched sibling donor • TCD—T cell depleted • GVHD—graft-versus-host disease • VOD—veno-occlusive disease • PHTN—pulmonary hypertension • TRM—transplant-related mortality

Accepted Sep 23, 2005.




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H. Lackner, C. Urban, P. Sovinz, M. Benesch, A. Moser, and W. Schwinger
Hemophagocytic lymphohistiocytosis as severe adverse event of antineoplastic treatment in children
Haematologica, February 1, 2008; 93(2): 291 - 294.
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