Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure se ems possible only by allogeneic bone marrow transplantation (BMT), but matc hed sibling donors (MSD) are restricted and high mortality rates are associ ated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD, Five patients had signs of active HL H at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulp han, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivef old graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild i n 10, and moderate or severe in two patients undergoing unrelated transplan ts. One patient with URD experienced graft failure and was retransplanted o n day 37. Major toxicities were hepatic veno-occlusive disease in five, cap illary leak syndrome in two, pneumonia in three, sepsis in one, severe muco sitis in one and seizures in two patients. All patients are alive without H LH after a median follow-up of 24.5 months. One patient has chronic GVI-ID, another patient has severe retardation. Three patients show slight to mode rate development delay. These results indicate that in HLH, BMT from matche d unrelated donors should be performed. Incomplete resolution of disease ac tivity need not impede a successful outcome.