Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Abstract

Introduction Acute GVHD is one of the most common serious complications of allogeneic HSCT and remains a leading cause of mortality in HSCT recipients all over the world. Various publications showed the association of acute GVHD with higher risk of infectious complications. There is lack of data on risk factors for developing an episode of infection and spectrum of infections in patients with acute GVHD after allogeneic HSCT. Objective to determine the risk factors and spectrum of infectious complications in patients with acute GVHD after allogeneic HSCT. Methods An ambispective observational study was performed to evaluate the risk factors and characteristics of infectious complications in adult patients having acute GVHD after HSCT. Proven case of infection (bacterial, viral or fungal) was taken as a primary outcome in the study. There were totally 68 adult patients with II-IV grades of acute GVHD after allogeneic HSCT included in the study. As a covariates included in multivariate analysis were taken: procedure of MCSs transplantation; type of allogeneic HSCT (related/non-related), main disease progression, absolute neutrophil count (ANC) on the first day of infectious complication, GVHD-involved organs. Results Microbiological data concerning the causes of infectious complications in patients with acute GVHD has shown the major impact of viral infections (CMV) and invasive pulmonary aspergillosis. There were no bloodstream infections caused by Candida spp. registered in the study. Bacterial infections were mostly presented by bloodstream infections (caused by K. pneumoniae, E. faecalis, E. coli) and pneumonia. Progression of main disease (OR 5.52; 95% CI 1.21-25.06; p=0.0270) was found to be an independent risk factor for development of invasive pulmonary aspergillosis and bacterial infectious complications. Patients with hematopoietic stem cell transplant from unrelated donor remain in a group with high risk for bacterial infections in case of developing acute GVHD (OR 3.50; 95% CI 1.12-10.97; p=0.0316). The procedure of MSCs transplantation as a potential treatment of GVHD showed no influence on risk of invasive aspergillosis (OR 3.25; 95% CI 0.64-16.47; p=0.1536) or CMV-reactivation (reciprocal OR 0.42; 95% CI 0.12-1.49; p=0.1802) in the study. Conclusion Among the most frequent infections in acute GVHD we have described CMV, invasive aspergillosis and bacterial infections. Among risk factors for infectious complications in patients with acute GVHD are progression of main disease and neutropenia below 500 cells/mm3 (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia). MSCs transplantation as a treatment strategy for acute GVHD has shown no statistically significant association with risk of infectious complications in a performed multivariate analysis.