TY - JOUR

T1 - C-Reactive Protein Levels at Diagnosis of Acute Graft-versus-Host Disease Predict Steroid-Refractory Disease, Treatment-Related Mortality, and Overall Survival after Allogeneic Hematopoietic Stem Cell Transplantation

AU - Minculescu, Lia

AU - Kornblit, Brian Thomas

AU - Friis, Lone Smidstrups

AU - Schiødt, Ida

AU - Petersen, Soeren Lykke

AU - Andersen, Niels Smedegaard

AU - Sengeloev, Henrik

PY - 2018

Y1 - 2018

N2 - Acute graft-versus-host disease (aGVHD) remains a cause of excessive morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Primary treatment consists of high-dose corticosteroids, but a small group of patients develop steroid-refractory disease, and their prognosis is especially poor. There is experimental evidence that coexisting inflammation aggravates aGVHD. Because C-reactive protein (CRP) is a systemic inflammatory marker, we aimed to investigate whether plasma CRP concentrations at the diagnosis of aGVHD can predict the risk of failing first-line therapy and developing steroid-refractory disease. We retrospectively studied 461 patients who underwent HSCT between 2010 and 2015. aGVHD grade II-IV was diagnosed in 148 patients (32%). CRP level and total white blood cell, lymphocyte, and neutrophil counts were available for all patients at the time of aGVHD diagnosis. According to local protocol, patients with failed response to high-dose steroid therapy (2 mg/kg) were treated with the TNF-α inhibitor infliximab and categorized as having steroid-refractory disease. Of 148 patients with grade II-IV aGVHD, 28 (19%) developed steroid-refractory disease. In these patients, plasma CRP concentration at diagnosis ranged between <1 and 253 mg/L. CRP levels were significantly higher in patients who developed steroid-refractory disease compared with those who responded to high-dose corticosteroid therapy (odds ratio, 1.50; 95% confidence interval, 1.18-1.93; P =.001). This translated into significantly increased transplantation-related mortality and decreased overall survival in the patients with high CRP levels. Total white blood cell, lymphocyte, and neutrophil counts were not associated with steroid resistance in the patients with aGVHD. These results suggest that CRP level at diagnosis is a valid predictor of the development of steroid-refractory disease in patients who develop grade II-IV aGVHD after HSCT.

AB - Acute graft-versus-host disease (aGVHD) remains a cause of excessive morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Primary treatment consists of high-dose corticosteroids, but a small group of patients develop steroid-refractory disease, and their prognosis is especially poor. There is experimental evidence that coexisting inflammation aggravates aGVHD. Because C-reactive protein (CRP) is a systemic inflammatory marker, we aimed to investigate whether plasma CRP concentrations at the diagnosis of aGVHD can predict the risk of failing first-line therapy and developing steroid-refractory disease. We retrospectively studied 461 patients who underwent HSCT between 2010 and 2015. aGVHD grade II-IV was diagnosed in 148 patients (32%). CRP level and total white blood cell, lymphocyte, and neutrophil counts were available for all patients at the time of aGVHD diagnosis. According to local protocol, patients with failed response to high-dose steroid therapy (2 mg/kg) were treated with the TNF-α inhibitor infliximab and categorized as having steroid-refractory disease. Of 148 patients with grade II-IV aGVHD, 28 (19%) developed steroid-refractory disease. In these patients, plasma CRP concentration at diagnosis ranged between <1 and 253 mg/L. CRP levels were significantly higher in patients who developed steroid-refractory disease compared with those who responded to high-dose corticosteroid therapy (odds ratio, 1.50; 95% confidence interval, 1.18-1.93; P =.001). This translated into significantly increased transplantation-related mortality and decreased overall survival in the patients with high CRP levels. Total white blood cell, lymphocyte, and neutrophil counts were not associated with steroid resistance in the patients with aGVHD. These results suggest that CRP level at diagnosis is a valid predictor of the development of steroid-refractory disease in patients who develop grade II-IV aGVHD after HSCT.

KW - Allogeneic hematopoietic stem cell transplantation

KW - C-reactive protein

KW - Graft-versus-host disease

KW - Inflammation

U2 - 10.1016/j.bbmt.2017.10.025

DO - 10.1016/j.bbmt.2017.10.025

M3 - Journal article

C2 - 29074374

AN - SCOPUS:85035105939

VL - 24

SP - 600

EP - 607

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 3

ER -