HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS - EXPERIENCE AT 2 UK CENTERS

Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappr opriate macrophage activation. Both familial and sporadic forms, which may be infection-associated, are recognized. Between 1985 and 1991 we treated 23 cases of HLH (12 male, 11 female). There were eight famili al cases, defined by a previously affected sibling and/or history of c onsanguinity, age 3 d to 15 months at presentation. The age of the rem aining 15 cases varied from 1 month to 9.5 years. A potential viral tr igger was identified in four cases (EBV, two; parvovirus B19, one; ech ovirus II, one) including one familial case. Six of eight (75%) patien ts who received supportive care alone, including all four familial cas es, died within 6 months of presentation. Both long-term survivors in this group presented at an older age (7.5 and 8 years) and had proven or suspected virus-associated HLH. 15 patients were treated with etopo side (150-250 mg/m(2) days 1-3 every 21 d) and methylprednisolone; 10 patients received intrathecal methotrexate in addition. In nine (60%) of these cases a complete (six) or partial (three) response was achiev ed, though one child suffered a fatal 'tumour lysis' syndrome. Overall mortality in the treated group was 66.6%, being highest (75%) in pati ents under 2 years at presentation compared to 33% in those over 2 yea rs. Two of three familial and one of five sporadic cases relapsed-and died 3 d to 20 months from diagnosis. Only one familial case survives at follow-up of II months. Of the five remaining survivors, two receiv ed allogeneic bone marrow transplantation (one matched related, one ha ploidentical) and are alive at 11 and 29 months. Three cases aged 2.5, 7.5 and 9.5 years remain in remission at 11, 20 and 25 months respect ively. The high mortality of HLH supports a role for allogeneic BMT in selected cases, particularly those with a familial basis or under 2 y ears at presentation.