HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS - REPORT OF 122 CHILDREN FROM THE INTERNATIONAL REGISTRY

Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disea se of early infancy. The diagnosis of HLH is frequently delayed or mad e at autopsy because no genetic or biologic marker has been identified . To improve the classification and treatment of HLH, the Histiocyte S ociety has established an 'International Registry for HLH'. Data colle cted included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypo fibrinogenemia, and hemophagocytosis without evidence of malignancy) w ere used for patient selection. One hundred and twenty-two patients (6 1 males, 61 females) were enrolled from 17 centers in II countries. Th e rate of parental consanguinity was 24%. A positive family history wa s reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference be tween familial and sporadic cases. Age at onset was similar in affecte d sibs from 10 of 14 families, but in four up to 3-year differences we re observed. Hemophagocytosis was present at diagnosis in 75%, An asso ciated infection (usually by common viral pathogens) was reported in 5 0 of the 122 (41%) cases, of which 25 had familial disease. Natural ki ller activity was impaired in 36 of 37 patients studied. Chromosome an alysis was normal in all tested patients, A decreased frequency of HLA -B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were obs erved. The estimated 5-year survival (SE) was 21% (18.7) for all patie nts. It was 66% (37.8) for patients who received allogeneic bone marro w transplant and 10.1% (9.6) for patients treated with chemotherapy al one (P = 0.0001). None of the previously proposed prognostic indicator s (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.