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Graft-Versus-Host Disease

Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning

Bone Marrow Transplantation volume 45, pages 1442–1448 (2010)Cite this article

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Abstract

Acute GVHD has remained a significant cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The role of TNF-α in the biology of acute GVHD after nonmyeloablative conditioning has not been studied thus far. Here, we measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-α in 106 patients before the start of the conditioning regimen (baseline) and 7 days after allogeneic HCT with nonmyeloablative conditioning. The nonmyeloablative regimen consisted of 2 Gy TBI alone (n=15), 2 Gy TBI plus fludarabine 90 mg/m2 (n=73), or 4 Gy TBI plus fludarabine 90 mg/m2 (n=18). TNFR1 levels increased significantly from baseline to day 7 after nonmyeloablative HCT (P<0.0001). Patients conditioned with 4 Gy TBI had higher TNFR1 day 7/baseline ratio than those conditioned with 2 Gy TBI (median 1.65 versus 1.25; P=0.01). In a multivariate Cox model, high TNFR1 day7/baseline ratio was associated with grades II–IV (HR=2.2, P=0.01) and grades III–IV (HR=2.9, P=0.007) acute GVHD, but had no impact on overall survival (P=0.8). In summary, our data suggest that nonmyeloablative conditioning induces the generation of TNF-α, and that the magnitude of TNF-α generation depends on the conditioning intensity (2 Gy versus 4 Gy TBI). Further, assessment of TNFR1 levels before and on day 7 after nonmyeloablative HCT provided useful information on subsequent risk of experiencing acute GVHD.

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Acknowledgements

We are grateful to physicians, physicians’ assistants, and clinical staff for their dedicated care of the patients. FB is a senior research associate and YB a research director of the National Fund for Scientific Research (F.R.S.-FNRS) Belgium. The study was in part supported by funds from the FNRS, the Anti-Cancer Center from the University of Liége, and by the Belgian Federation against Cancer (FBC).

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Author notes

  1. E Willems and S Humblet-Baron: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, CHU of Liége, Liége, Belgium

    E Willems, O Dengis, Y Beguin & F Baron

  2. Groupe Interdisciplinaire de Génoprotéomique Appliquée (Giga)-Research, Hematology Unit, University of Liége, Liége, Belgium

    E Willems, S Humblet-Baron, O Dengis, Y Beguin & F Baron

  3. Department of Statistics, University of Liége, Liége, Belgium

    L Seidel

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Willems, E., Humblet-Baron, S., Dengis, O. et al. Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. Bone Marrow Transplant 45, 1442–1448 (2010). https://doi.org/10.1038/bmt.2009.360

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