Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients.
OBJECTIVE
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 > or = 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.
Ouachée-Chardin
Marie
M
Department of Pediatric Immuno-Hematology, Necker-Enfants Malades Hospital, Paris, France.
Elie
Caroline
C
de Saint Basile
Geneviève
G
Le Deist
Françoise
F
Mahlaoui
Nizar
N
Picard
Capucine
C
Neven
Bénédicte
B
Casanova
Jean-Laurent
JL
Tardieu
Marc
M
Cavazzana-Calvo
Marina
M
Blanche
Stéphane
S
Fischer
Alain
A
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006648:Histocompatibility; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000401:mortality / Q000628:therapy*; D008297:Male; D015996:Survival Rate; D019172:Transplantation Conditioning