Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia.
The association of mixed (donor/host) chimerism with graft-versus-host disease (GVHD), graft rejection, disease recurrence and survival was investigated in 116 patients with aplastic anemia and 197 patients with chronic myelogenous leukemia (CML) transplanted with unmodified marrow from an HLA-identical sibling donor of opposite sex. Patients with aplastic anemia were conditioned with cyclophosphamide (CY), patients with CML were conditioned with a combination of CY and total body irradiation (TBI) or busulfan. Sixty-three of the patients with aplastic anemia (54%) and 100 patients with CML (51%) were categorized as mixed chimeras based on the concurrent presence of donor and host lymphohematopoietic cells 14 days or later after transplantation. The TBI dose used for conditioning was inversely correlated with the development of mixed chimerism (P < 0.0001) among CML patients. No other patient- or transplant-related parameter was identified which contributed significantly to the development of mixed chimerism. The incidence of rejection was higher but not significantly so in patients with aplastic anemia who were mixed chimeras. The incidence of leukemic relapse in patients with CML who were mixed chimeras was increased only if mixed chimerism occurred after day 100 (P = 0.015). The incidence of acute GVHD (grades II-IV) was lower in mixed chimeras than in complete chimeras, but this difference was statistically significant only for patients with aplastic anemia given single-agent GVHD prophylaxis (P = 0.0008). Mixed chimeras in that group also had a better survival than complete chimeras, while no significant difference was observed in patients with aplastic anemia given drug combinations for GVHD prophylaxis. Among patients with CML, both overall survival (P = 0.03) and relapse-free survival (P = 0.04) were significantly superior in mixed than in complete chimeras. Thus, mixed chimerism was frequent among patients with aplastic anemia and with CML and was not uniformly associated with graft failure or leukemic relapse. The interaction between conditioning regimen, GVHD prophylaxis and chimerism are complex. The survival advantage of mixed chimeras is only in part related to a lower incidence of GVHD and other factors are likely to contribute.
Huss
R
R
Clinical Research Division, Fred Hutchinson Cancer Research Center. Seattle, WA 98104, USA.
Deeg
H J
HJ
Gooley
T
T
Bryant
E
E
Leisenring
W
W
Clift
R
R
Buckner
C D
CD
Martin
P
P
Storb
R
R
Appelbaum
F R
FR
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology* / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002678:Chimera / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D006680:HLA Antigens; D006801:Humans; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous
D006680:HLA Antigens