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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1150-1156
Graft-versus-host disease and donor-directed hemagglutinin
titers after ABO-mismatched related and unrelated marrow
allografts: evidence for a graft-versus-plasma cell effect
Marco Mielcarek,
Wendy Leisenring,
Beverly Torok-Storb, and
Rainer Storb
From the Transplantation Biology and Clinical Statistics Programs,
Clinical Research Division, Fred Hutchinson Cancer Research Center; and
the Departments of Medicine and Biostatistics, University of
Washington, Seattle, WA.
The gradual disappearance of host antidonor isohemagglutinins after
major ABO-mismatched hematopoietic stem cell (HSC) allografts has been
attributed to the gradual destruction of host plasma cells by
graft-versus-host effects. To corroborate this hypothesis, we
retrospectively analyzed results from 383 major or major/minor ABO-mismatched unrelated and related HSC allografts performed between
1983 and 1998. All patients were conditioned by high-dose pretransplant
therapy and given methotrexate/cyclosporine for graft-versus-host
disease (GvHD) prophylaxis. Of the 383 patients, 155 had HLA-matched
related and 228 had unrelated grafts. We asked whether unrelated
recipients experienced a more rapid disappearance of isohemagglutinins
than related recipients, and whether, within the groups of related and
unrelated recipients, the titer disappeared faster in patients with
GvHD than in those without GvHD. The median time to reach undetectable
antidonor IgG and IgM titers was significantly shorter in unrelated
recipients (46 versus 61 days; P = .016). In addition,
related recipients with GvHD had a 2.2-fold increased likelihood
(1.12-4.39,95% CI; P = .02) of reaching undetectable titers within 100 days than patients without GvHD. The persistence of
antidonor isohemagglutinins led to significantly increased red blood
cell (RBC) transfusion requirements in the ABO-mismatched related
patients compared with ABO-matched counterparts. However, time to
neutrophil and platelet engraftment, incidence of GvHD, and survival
were not influenced by ABO incompatibility. In conclusion, our results
corroborate the hypothesis that the rate of disappearance of antidonor
isohemagglutinins after ABO-mismatched allogeneic HSC grafts is
influenced by the degree of genetic disparity between donor and
recipient, suggesting a graft-versus-plasma cell effect.
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