UNRELATED-DONOR BONE-MARROW TRANSPLANTATION FOR PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKEMIA IN CHILDREN - EXPERIENCE OF 8EUROPEAN COUNTRIES

From September 1988 to December 1995 forty-four children (age <17 year s) with Phl Chronic Myelogenous Leukemia (CML) received unrelated dono r marrow transplantation in 8 European Countries, Thirty-three evaluab le children were typed by serological testing on HLA-A, B, and DR loci , Thirty of them were further DR subtyped by DNA techniques, Twenty-fo ur pairs were 6 antigen matched, Seven were mismatched at 1 locus (2 p airs at A and B loci respectively and 3 at DR locus), Two out of 30 pa irs evaluated by molecular biology had one antigen mismatched at DRB1 locus, Thirty-two (96%) out of 33 evaluable children reached a sustain ed granulocyte count higher than 0.5 x 10(9)/I at a median of 21 (rang e 14-88) days after transplantation. The remaining child failed to eng raft. Two children developed secondary graft failure. A platelet count greater than 50 x 10(9)/I sustained for at least seven consecutive da ys without transfusion support was reached at a median of 25 (range: 2 0-144) days by 24 out of 33 evaluable children and 9 children never re covered to above 50 x 10(9)/I. Twenty-one out of 33 evaluable children developed grade I (n = 7), grade II (n = 8), grade III (n = 2) or gra de IV (n = 4) acute GvHD (63%), Seven of the 30 evaluable children sur viving more than 100 days developed chronic GvHD (20%) which was limit ed in 3 cases and extensive in 3, Relapse occurred in 3 of the 44 (7%) children at 2 to 24 months (median 14), Twenty-four month relapse rat e was 14%, Seventeen out of 44 children (38%) died of transplant relat ed mortality (TRM), 4 (9%) of secondary tumor, 4 (9%) of infections, 3 (7%) of organ failure, 1 (2%) of interstitial pneumonia, 5 (11%) of u nknown causes, Actuarial TRM was 61% for children grafted before Decem ber 1991 and 33% for children grafted after January 1992 (p =.01). EFS was 49.7%; it was 65% for children receiving more than 3.5 x 10(9)/Kg MNC.