Unrelated donor marrow transplantation for inborn errors

From December 1989 to December 1997 40 children aged 1 year to 19 years with inborn errors other than severe combined immunodeficiencies underwent unrelated donor (UD) bone marrow transplantation (BMT) in one of 10 institutions of the Italian Bone Marrow Transplant Group participating in this program. The diseases leading to BMT included Fanconi Anemia (10), Thalassemia (8), Wiskott Aldrich syndrome (5), haemophagocytic lymphohystiocytosis (6), osteopetrosis (3), storage diseases (6), Chediak Higashi syndrome (1), Schwachman syndrome (1), Thirty-three pairs were A, B, DRB1 matched. Three pairs were one antigen mismatched and one pair was two antigens mismatched. The remaining three pairs lacked information on molecular biology. Twelve children underwent a preparative regimen including radiotherapy. The remaining 28 children were conditioned with a chemotherapy regimen which included Busulfan. GVHD disease prophylaxis included CSA and MTX alone (9) or associated with ALG (17) or in vivo Campath 1G (12). The remaining two children received CSA alone. Thirty-five children showed donor engraftment; three children with thalassemia and one with osteopetrosis failed to engraft. Five children developed secondary graft failure. Actuarial 5 year disease-free survival was 62%; grade III-IV acute GvHD developed in seven of 38 evaluable children (18%); chronic GvHD developed in seven of 27 evaluable children (26%). We confirm that Wiskott Aldrich syndrome, HLH, and osteopetrosis represent an absolute indication for UD-BMT. Prognosis of UD-BMT for FA could improve in children grafted in an early phase, but a better preparative regimen has to be identified. UD-BMT in thalassemia is acceptable only in a restricted subset of patients selected for poor compliance to therapy.