Unrelated 5/6-locus matched umbilical cord blood transplantation in a 23-month-old child with hemophagocytic lymphohistiocytosis.

A diagnosis of familial hemophagocytic lymphohistiocytosis (FHL) was established in an 18-month-old boy who presented with prolonged fever of unknown origin, severe pancytopenia, hepatosplenomegaly and hypofibrinogenemia. Serum levels of ferritin and soluble interleukin-2 receptor (SIL2R) were highly elevated, and the number of natural killer (NK) cells was markedly decreased. An allogeneic stem cell donor was neither found in the family nor in unrelated donor registries; however, an umbilical cord blood (UCB) donor request revealed a 5/6 HLA-matched UCB. After conditioning with busulphan 16 mg/kg body weight (BW), cyclophosphamide 120 mg/kg BW and etoposide (VP-16) 900 mg/m2 the patient received 19.6 x 10(7)UCB nucleated cells/kg BW. White blood count (WBC) reached 1.0 x 10(9)/l on day +45. Chimerism studies showed full and permanent hematopoietic and lymphopoietic engraftment on day +16. However despite full engraftment the patient still experienced two severe relapses of his disease after stem cell transplantation with the highest ferritin level in the range of 10 3967 microg/l (n = 7-142). NK cell function appeared only 6 months after UCB transplantation followed by a decrease of FHL markers and resolution of disease activity. This clinical outcome indicates that unless competent immunologic engraftment after transplantation is established, FHL is capable of relapsing even if complete three-lineage engraftment is achieved.