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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1539-1542.
Prepublished online as a Blood First Edition Paper on May 23, 2008; DOI 10.1182/blood-2008-02-138867.


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TRANSPLANTATION

Brief Report

Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival

Sung W. Choi1,2, Carrie L. Kitko1,2, Thomas Braun3, Sophie Paczesny4, Gregory Yanik1,2, Shin Mineishi2, Oleg Krijanovski2, Dawn Jones1, Joel Whitfield4, Kenneth Cooke1, Raymond J. Hutchinson1, James L. M. Ferrara1,2, and John E. Levine1,2

Departments of1 Pediatrics and 2 Internal Medicine, Blood and Marrow Transplantation Program, 3 Biostatistics, and 4 Comprehensive Cancer Center, University of Michigan, Ann Arbor

Acute graft-versus-host disease (GVHD) remains a significant cause of mortality after hematopoietic cell transplantation (HCT). Tumor necrosis factor–alpha (TNF-{alpha}) mediates GVHD by amplifying donor immune responses to host tissues and by direct toxicity to target organs. We measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-{alpha} in 438 recipients of myeloablative HCT before transplantation and at day 7 after transplantation. Increases in TNFR1 levels more than or equal to 2.5 baseline correlated with eventual development of GVHD grade 2 to 4 (58% vs 32%, P < .001) and with treatment-related mortality (39% vs 17%, P < .001). In a multivariate analysis including age, degree of HLA match, donor type, recipient and donor sex, disease, and status at HCT, the increase in TNFR1 level at day 7 remained a significant predictor for outcome. Measurement of TNFR1 levels early after transplantation provides independent information in advance of important clinical outcomes, such as GVHD and death.


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