Bone marrow transplantation for severe aplastic anemia from genotypically HLA-nonidentical relatives. An update of the Seattle experience.
This report updates the results of marrow transplantation at the Fred Hutchinson Cancer Research Center for patients with severe aplastic anemia whose donors were HLA-nonidentical relatives. Between 1970 and 1993, 40 patients received transplants for severe aplastic anemia from related donors other than HLA genotypically matched siblings. Nine patients (group 1) were conditioned with cyclophosphamide (Cy) at 50 mg/kg for 4 doses and received marrow from phenotypically HLA-matched relatives. With the exception of one accidental death, all patients are alive and disease free 3-18 years after transplantation. Thirty-one patients received marrow from HLA-mismatched relatives who differed by one or more loci. Fifteen of these patients (group 2) received Cy at 50 mg/kg for 4 doses without total body irradiation (TBI) and none survived. Because of failure to sustain engraftment in 9 of 14 evaluable patients in group 2, the regimen for HLA-mismatched patients was changed in 1984 to include Cy at 60 mg/kg for 2 doses and TBI was added at 1200 cGy to increase immunosuppression (group 3). Sixteen patients in group 3 received marrow grafts after failure to respond to immunosuppressive therapy. Eight of the 16 patients in group 3 remain alive without disease between 1.5 and 11.3 years after transplantation. In conclusion, transplants from phenotypically HLA-identical related donors can be carried after Cy alone and results are comparable to those observed with genotypically HLA-identical siblings. Transplants from related donors mismatched for one or more HLA loci require a more intensive conditioning regimen, for example, one containing TBI, to achieve sustained engraftment.
Wagner
J L
JL
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Deeg
H J
HJ
Seidel
K
K
Anasetti
C
C
Doney
K
K
Sanders
J
J
Sullivan
K M
KM
Storb
R
R
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D014481:United States
D006680:HLA Antigens