Haemophagocytic lymphohistiocytosis: experience at two U.K. centres

Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappropriate 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 familial cases, defined by a previously affected sibling and/or history of consanguinity, age 3 d to 15 months at presentation. The age of the remaining 15 cases varied from 1 month to 9.5 years. A potential viral trigger was identified in four cases (EBV, two; parvovirus B19, one; echovirus II, one) including one familial case. Six of eight (75%) patients who received supportive care alone, including all four familial cases, 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 etoposide (150-250 mg/m2 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 achieved, though one child suffered a fatal 'tumour lysis' syndrome. Overall mortality in the treated group was 66.6%, being highest (75%) in patients under 2 years at presentation compared to 33% in those over 2 years. 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 11 months. Of the five remaining survivors, two received allogeneic bone marrow transplantation (one matched related, one haploidentical) 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 respectively. The high mortality of HLH supports a role for allogeneic BMT in selected cases, particularly those with a familial basis or under 2 years at presentation.