Unrelated donor marrow transplantation for genetic diseases

From December '89 to July '96, 36 children aged 1 month-9 years with genetic diseases underwent BMT from unrelated donor (UD) in one of the 7 Italian Institutions participating in this program. The diseases leading to BMT included immunodeficiencies (17), Fanconi Anemia (7), storage diseases (6), thalassemia (3), FEL (2) and osteopetrosis (1). Twenty-seven pairs were A, B, DRB1 matched. The remaining 9 pairs received the marrow from a donor mismatched for one (5) or more (4) antigens. Nine patients received a radiation containing regimen, 26 patients were conditioned with chemotherapy alone, the remaining patient was infused with donor marrow without any conditioning therapy. GvHD prophylaxis included CSA, MTX, and serotherapy (ALG or 'in vivo' Campath 1G) prior to BMT in 23 cases, CSA and MTX in 4 cases, CSA alone (7) or in combination with T-cell depletion (2) in the remaining 9 cases. Thirty-five children (97%) showed donor engraftment; the remaining child failed to engraft. Four children developed secondary graft failure. Actuarial 2 year disease-free survival was 57%; grade III-IV acute GvHD developed in 7 of 35 evaluable patients (20%); chronic GvHD developed in 5 of 22 (23%). We conclude that severe immunodeficiencies, FEL and osteopetrosis represent an absolute indication for UD-BMT. Prognosis of UD BMT for FA could improve in patients grafted in an early phase, UD BMT in thalassemia is acceptable only in a restricted subset of patients, selected for very serious reasons such as poor compliance to desferoxamine or alloimmunization to minor blood group antigens.