10 Changes in TNFR1 Levels in the First Week Post-Myeloablative Allogeneic BMT Correlate with GVHD and TRM in Pediatric Pts.

摘要

Tumor necrosis factor (TNF) plays a crucial role in the pathogenesis of graft-vs-host disease (GVHD), the major cause of treatment-related mortality (TRM) after allogeneic bone marrow transplantation (BMT). We tested the hypothesis that early rises in TNF (on day 7 following BMT) predict the development of significant GVHD and TRM. Ratios of soluble TNF receptor 1 (TNFR1) levels (day 7 level/pre-BMT level) was used as a surrogate marker for TNF in 440 myeloablative allogeneic BMT pts with a median age of 42y (range 0-65y). There were 269 (61%) related donors pts and 171 (39%) unrelated donors pts. 82 pts (19%) of this cohort were children 17y and younger of whom 38 were related donor pts (46%), 38 unrelated donor pts (46%) and 6 cord blood pts (8%). The median day of onset of GVHD 2-4 was 27d. For the entire cohort, the mean day 7 TNFR1 ratio correlated with severity of GVHD (p<0.001). When analyzed for pediatric pts only, higher TNFR1 ratio continued to correlate with increasing severity of GVHD (p = 0.01). The highest quartile of day 7 TNFR1 ratios also strongly correlated with likelihood of GVHD 2-4, 1yTRM, and 1y survival in the complete cohort and children only.We conclude that the magnitude of rise in early post-transplant TNFR1 ratios correlates with the subsequent severity of GVHD, TRM and survival. These informative changes are detectable often two to three weeks in advance of clinical manifestations of GVHD and may therefore provide the basis for development of a predictive laboratory test.