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What role for prednisone in prevention of acute graft-versus-host disease
in patients undergoing marrow transplants?
R Storb, M Pepe, C Anasetti, FR Appelbaum, P Beatty, K Doney, P Martin, P Stewart, KM Sullivan and R Witherspoon
Division of Clinical Research Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
One hundred forty-seven consecutive patients with leukemia, myelodysplastic
syndrome, or aplastic anemia were treated by marrow grafts from
genotypically HLA-identical siblings (n = 122) or HLA- haploidentical
family members (n = 25). Haploidentical recipients differed from their
donors for no more than one HLA locus on the nonshared haplotype. All were
given postgrafting immunosuppression with a combination of methotrexate and
cyclosporine. In a randomized study we explored whether prednisone
administered from day 0 through 35 along with methotrexate/cyclosporine
could improve prevention of acute graft- versus-host disease (GVHD). The
GVHD incidence in patients not given prednisone was comparable with that
previously reported with methotrexate/cyclosporine. Unexpectedly,
significant increases in acute and also chronic GVHD were seen in
HLA-identical recipients administered prednisone, but not in the small
number of patients administered HLA-nonidentical grafts. However, the
resultant increase in transplant-related mortality in patients administered
prednisone was offset by an increase in leukemic relapse in patients not
administered prednisone, presumably related to the absence of a
graft-versus- leukemia effect. Therefore, overall disease-free survival of
the two groups of patients was comparable, with slightly more than 50% of
the patients being alive at more than 2 years after transplantation. We
speculated that prednisone adversely affected GVHD prophylaxis, interfering
with methotrexate's cell cycle-dependent suppression of donor lymphocyte
proliferation in response to host antigens. In a pilot study we explored
whether beginning prednisone on day 15, after completion of methotrexate
administration, would avoid this adverse effect. The GVHD incidence in
patients administered methotrexate/cyclosporine along with "late"
prednisone was comparable with that in patients not administered
prednisone. We conclude that methotrexate/cyclosporine is effective in
decreasing the incidence of grade II through IV GVHD, and that the addition
of prednisone to this regimen is not beneficial in recipients of
HLA-identical marrow grafts.
Volume 76,
Issue 5,
pp. 1037-1045,
09/01/1990
Copyright © 1990 by The American Society of Hematology
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Related Letter in Blood Online:
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Cyclosporine (CSP) or CSP plus methylprednisolone for graft-versus-host-disease prophylaxis in patients with high-risk lymphohemopoietic malignancies: long-term follow-up of a randomized trial
- H. Joachim Deeg, Mary E. D. Flowers, Wendy Leisenring, Frederick R. Appelbaum, Paul J. Martin, and Rainer F. Storb
Blood 2000 96: 1194-1196.
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