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.


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.
Cesaro
Simone
S
Oncoematologia Pediatrica, Dipartimento di Pediatria, Università di Padova, Via Giustiniani 3,35128, Padova Italy. simone.cesaro@unipd.it
Locatelli
Franco
F
Lanino
Edoardo
E
Porta
Fulvio
F
Di Maio
Lucia
L
Messina
Chiara
C
Prete
Arcangelo
A
Ripaldi
Mimmo
M
Maximova
Natasha
N
Giorgiani
Giovanna
G
Rondelli
Roberto
R
Aricò
Maurizio
M
Fagioli
Franca
F