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.
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.
Choi
Sung W
SW
Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI 48109-5942, USA.
Kitko
Carrie L
CL
Braun
Thomas
T
Paczesny
Sophie
S
Yanik
Gregory
G
Mineishi
Shin
S
Krijanovski
Oleg
O
Jones
Dawn
D
Whitfield
Joel
J
Cooke
Kenneth
K
Hutchinson
Raymond J
RJ
Ferrara
James L M
JL
Levine
John E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019653:Myeloablative Agonists; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha