title: Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.
abstract: Acute GVHD has remained a significant cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The role of TNF-alpha 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-alpha 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-alpha, and that the magnitude of TNF-alpha 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.
authors.affiliation: Division of Hematology, Department of Medicine, CHU of Liége, Liége, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Willems
authors.forename: S
authors.initials: S
authors.lastname: Humblet-Baron
authors.forename: O
authors.initials: O
authors.lastname: Dengis
authors.forename: L
authors.initials: L
authors.lastname: Seidel
authors.forename: Y
authors.initials: Y
authors.lastname: Beguin
authors.forename: F
authors.initials: F
authors.lastname: Baron
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D006402:Hematologic Diseases / Q000401:mortality* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012008:Recurrence; D012269:Ribosomal Proteins; D012307:Risk Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D012269:Ribosomal Proteins; C087267:ribosome releasing factor