☆ 4.2 Article

Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION (2020)

Journal

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

Volume 26, Issue 9, Pages 1670-1678

Publisher

ELSEVIER SCIENCE INC

DOI: 10.1016/j.bbmt.2020.06.006

Keywords

Haploidentical related donor hematopoietic cell transplantation; Cytokine release syndrome; Infections; Bacterial infections; Post-transplantation cyclophosphamide

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Abstract

An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity. In our study cohort, which was stratified into 3 groups by severity of CRS, 80% of the patients developed infections within 180 days of HCT. Significantly higher proportions of patients with CRS grade 2 (89%) and grade >= 3 (90%) than patients with CRS grade 0-1 (68%) had at least 1 infection in the first 100 days (P = .04). Bloodstream infections (BSIs) were seen more frequently in patients with CRS grade 2 and grade >= 3 in the first 6 months. Multivariable analysis for time to infection showed that CRS grade >= 3 was independently associated with an elevated risk of any infection compared with CRS grade 0-1 (hazard ratio [HR], 3.05; P = .007). CRS grade >= 3 was also associated with a higher hazard of viral (HR, 3.42; P = .04) and bacterial infections (HR, 2.83; P = .03) compared with CRS grade 0-1. After adjusting for time to neutrophil engraftment as a time-dependent covariate, CRS grade >= 3 still had a significant effect on viral infections (HR, 2.49; P = .03), but not on bacterial infections (HR, 1.32; P = .57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day +100 was higher in patients with severe CRS. Severe CRS developing after post-transplantation cyclophosphamide-based haploHCT is independently associated with viral infections and an increased risk of bacterial infections, likely through delayed neutrophil engraftment. (C) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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Invasive Yeast Infection after Haploidentical Donor Hematopoietic Cell Transplantation Associated with Cytokine Release Syndrome

Jessica S. Little, Roman M. Shapiro, Muneerah M. Aleissa, Austin Kim, Jun Bai Park Chang, David W. Kubiak, Guohai Zhou, Joseph H. Antin, John Koreth, Sarah Nikiforow, Corey S. Cutler, Rizwan Romee, Nicolas C. Issa, Vincent T. Ho, Mahasweta Gooptu, Robert J. Soiffer, Lindsey R. Baden

Summary: This study aimed to evaluate the incidence and risk factors for invasive fungal disease (IFD) after haploidentical donor hematopoietic cell transplantation (haploHCT). The identification of acute myelogenous leukemia and cytokine release syndrome (CRS) as risk factors for early invasive yeast infection (IYI) after haploHCT raises questions about their potential association with other infections. Recognition of key risk factors for infection may permit the development of individualized strategies for prevention and intervention.

TRANSPLANTATION AND CELLULAR THERAPY (2022)