TREATMENT OF FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS WITH BONE-MARROW TRANSPLANTATION FROM HLA GENETICALLY NONIDENTICAL DONORS

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic di sorder associated with the onset early in life of overwhelming activat ion of T lymphocytes and macrophages invariably leading to death. Allo geneic bone marrow transplantation (BM) from an HLA-identical related donor is the treatment of choice in patients with this disease. Howeve r, fewer than 20% of patients have a disease-free HLA-identical siblin g. BMT from HLA-nonidentical related donors has previously met with po or results, with graft rejection a major obstacle in all cases. We des cribe BMTs from HLA-nonidentical related donors (n = 13) and from a ma tched unrelated donor (n = 1) performed in two centers in 14 consecuti ve cases of FHL. Remission of disease was achieved before BMT in 10 pa tients. Marrow was T-cell-depleted to minimize graft-versus-host disea se (GVHD). Antiadhesion antibodies specific for the cu chain of the le ukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molec ules were infused pre-BMT and post-BMT to help prevent graft rejection , in addition to a conditioning regimen of busulfan (BU), cyclophospha mide [CP], end etoposide (VP16) or antithymocyte globulin (ATG). Susta ined engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-u p period of 8 to 69 months (mean, 331. Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-fr ee survival within the limitations of the small sample. We conclude th at an immunologic approach in terms of drugs used to obtain disease re mission and a conditioning regimen that includes antiadhesion molecule s in T-cell-depleted BMT from HLA genetically nonidentical donors is a n alternative treatment that warrants further study in FHL patients wh o lack a suitable HLA genetically identical donor. (C) 1997 by The Ame rican Society of Hematology.