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Evidence that sustained growth suppression of intestinal anaerobic bacteria
reduces the risk of acute graft-versus-host disease after sibling marrow
transplantation
DW Beelen, E Haralambie, H Brandt, G Linzenmeier, KD Muller, K Quabeck, HG Sayer, U Graeven, HK Mahmoud and UW Schaefer
Department of Bone Marrow Transplantation, University Hospital of Essen,
Germany.
The influence of intestinal bacterial decontamination on the occurrence of
grades II to IV acute graft-versus-host disease (GVHD) was retrospectively
analyzed in 194 predominantly adult patients treated by genotypically
identical sibling marrow transplantation under conditions of strict
protective isolation and intestinal antimicrobial decontamination.
Forty-five patients (23%) developed acute GVHD and univariate analysis
identified four features that significantly increased the risk for this
reaction: chronic myeloid leukemia as the underlying disease, as compared
with all other disease categories (P < .0001); female marrow donors for
male recipients, as compared with other gender combinations (P < .005);
ineffective, as compared with sustained growth suppression of intestinal
anaerobic bacteria (P < .006); and methotrexate as the sole
immunoprophylactic compound, as compared with cyclosporine containing
regimens (P < .05). Using the duration of anaerobic growth suppression
as a time-dependent explanatory variable, proportional hazards regression
analysis confirmed these features as independent predictors for acute GVHD
with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to
2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3
to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to
2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1
to 1.6) for the donor/recipient gender combination (P < .008),
respectively. Best subset selection modeling also identified the quality of
anaerobic decontamination as the third most important predictor for acute
GVHD, when all four significant features were included. Estimates of acute
GVHD stratified by the quality of anaerobic bacterial growth suppression
showed a strong influence of anaerobic decontamination in patients burdened
by at least one of the other unfavorable factors (P < .009). In
conclusion, this study provides strong evidence that sustained growth
suppression of intestinal anaerobic bacteria after clinical sibling marrow
transplantation can independently modulate the occurrence of grades II to
IV acute GVHD, which is in concordance with previous results from animal
transplantation models. Antimicrobial chemotherapy specifically targeted to
the intestinal anaerobic bacterial microflora may be complementarily useful
in preventing acute GVHD and should be investigated in a prospective trial.
Volume 80,
Issue 10,
pp. 2668-2676,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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