Matched unrelated donor marrow transplantation in patients with advanced acute leukemia

Patients with advanced acute leukemia (AL) have a poor prognosis with death due to disease or complications of therapy. High-dose chemoradiotherapy fo llowed by allogeneic marrow transplantation (BMT) has been used to overcome resistance of the leukemic clone resulting in long-term survival of up to 20%. Due to lack of suitable related donors BMT fi om an HLA-compatible unr elated donor (MUD) has been increasingly applied in these patients during t he last years. Between January 1991 and August 1997 twenty five patients wi th advanced acute myeloid (n=19) or lymphoid (n=6) leukemia, 11 males and 1 4 females, age 22 to 41 (median 32) years received MUD (n=22) or I-antigen mismatched unrelated donor (n=3) grafts. In four patients an autologous BMT had been performed previously. For conditioning all patients were given to tal body irradiation containing regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region compatibil ity was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by hybridizati on of amplified DNA with ligation based typing. In 2 patients HLA-DR typing was performed by two colour fluorescence cytotoxicity test and mixed lymph ocyte cultures. As of November 1997 10/25 patients (40%) are surviving leuk emia-free after a median observation time of 17 (range, 3; to 38) months. T ransplant-related mortality was an overall of 36% and 28% in patients recei ving their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 month s after BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse projected at 3 years was 35%. High-dose chemoradiotherapy follo wed by MUD marrow infusion has a curative potential for patients with advan ced acute leukemia and offers the chance of long-term leukemia-free surviva l.