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A retrospective analysis of therapy for acute graft-versus-host disease:
initial treatment
PJ Martin, G Schoch, L Fisher, V Byers, C Anasetti, FR Appelbaum, PG Beatty, K Doney, GB McDonald and JE Sanders
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
We have reviewed results of therapy in 740 patients with grades II-IV acute
graft-versus-host disease (GVHD) after allogeneic marrow transplantation.
At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had
liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was
with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte
globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n =
633) or in combination (n = 107). Parameters of GVHD severity in each organ
were recorded weekly, and evaluation of response was made using values at
the initiation of secondary treatment or, for patients without such
treatment, using values on day 29 of primary treatment or the last recorded
value before death, whichever occurred first. Minimal criteria for
improvement or progression were defined for each organ, but no attempt was
made to define liver or gut outcome if another complication such as
venocclusive disease or infectious enteritis was present. Improvement rates
were 43% for skin disease, 35% for evaluable liver disease and 50% for
evaluable gut disease. Overall complete or partial responses were seen in
44% of patients. Multivariate analyses were carried out to identify
patient, disease or treatment factors associated with likelihood of overall
improvement and likelihood of response in at least one organ. A similar
analysis was also carried out to identify covariates associated with time
to treatment failure (defined as initiation of secondary therapy or death
not due to relapse of malignancy). In all three models, GVHD prophylaxis
using cyclosporine combined with methotrexate was associated with favorable
GVHD treatment outcome compared to prophylaxis with either agent alone, and
treatment with glucocorticoids or cyclosporine was more successful than
treatment with ATG. Other factors associated with unfavorable outcome in
the model of time to treatment failure and also entered in one of the
response models were recipient HLA disparity with the donor, presence of a
liver complication other than GVHD, and early onset of GVHD. Results of
this analysis indicate that glucocorticoids represent the best initial
therapy available for treatment of acute GVHD, although much room for
improvement remains.
Volume 76,
Issue 8,
pp. 1464-1472,
10/15/1990
Copyright © 1990 by The American Society of Hematology
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