PARTIAL ENGRAFTMENT OF DONOR BONE-MARROW CELLS ASSOCIATED WITH LONG-TERM REMISSION OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

We used polymerase chain reaction amplification of minisatellite seque nces or of a Y chromosome-specific sequence and Southern blotting to a nalyse long-term engraftment (12-82 months) after bone marrow transpla ntation (BMT) for familial haemophagocytic lymphohistiocytosis (FHL). Six children aged from 1 to 18 months were transplanted with bone marr ow from an HLA-identical sibling in five cases and from an HLA-noniden tical related donor (one mismatched HLA antigen) in one. The condition ing regiment included VP 16-213 (900 mg/m2), busulfan (16 mg/kg), cycl ophosphamide (200 mg/kg) and, in one case, aracytine (2 g/m2). Four pa tients are alive without therapy more than 3 years after BMT; the othe r two relapsed 1 year after BMT. DNA was extracted from separated poly morphonuclear cells and mononuclear cells, as well as from separated E + and E- cells in one case and CD16+ (natural killer) and CD16- cells in two cases. Engraftment was partial in the four long-term survivors. Recipient cells were largely predominant in three of them as well as in one of the patients who relapsed (the donor also developed FHL 18 m onths after BMT). E+, E-, CD16+ and CD16- cells presented the same pat tern of chimaerism. Engraftment failed to occur in the patient who rec eived an HLA-nonidentical bone marrow. These results indicate that par tial engraftment is compatible with long-term remission of FHL and tha t the presence of a small proportion of cells of donor origin can prev ent FHL-related lymphocyte and macrophage activation.