Allogeneic bone marrow transplantation with related donors other than HLA MLC-matched siblings, and the use of antithymocyte globulin, prednisone, and methotrexate for prophylaxis of graft-versus-host disease.
Fifteen patients ranging in age from 1-29 years (median age 9 years) had bone marrow transplantations (BMT) from related donors other than HLA mixed lymphocyte culture (MLC) identical siblings. Donors were selected on the basis of HLA similarity and low reactivity in the MLC. Posttransplant immunosuppression consisting of methotrexate (MTX), antithymocyte globulin (ATG), and prednisone was used in an effort to decrease graft-versus-host disease (GVHD). Seven children were treated for aplastic anemia, 7 for hematologic malignancy, and 1 for osteopetrosis. Primary engraftment failure contributed to death in 3 patients, all of whom had aplastic anemia. Nine of 12 engrafted patients developed moderate-to-severe acute graft-versus-host disease. Of the 15 patients, 7 developed interstitial pneumonitis. Three patients demonstrated mixed chimerism (at or beyond 3 months posttransplant). Two of the seven patients treated for aplastic anemia are currently alive six months and more than five years posttransplant; the latter patient has chronic GVHD. Four of the seven patients treated for hematologic malignancy are currently alive more than 500 days posttransplantation. Three have chronic GVHD. Analysis of patient outcome according to the degree of similarity in histocompatibility testing revealed that patients with low reactivity in the MLC (less than 5% relative response in both directions) had a better prognosis (5/6, 83% long-term survival) than patients with maximum donor vs. recipient mixed lymphocyte culture relative response greater than 5% (1/9, 12% long-term survival), P = .016.
Filipovich
A H
AH
Ramsay
N K
NK
Arthur
D C
DC
McGlave
P
P
Kim
T
T
Kersey
J H
JH
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D014019:Tissue Donors
D000961:Antilymphocyte Serum; D006680:HLA Antigens; D011241:Prednisone; D008727:Methotrexate