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Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2024 Mar;59(3):373-379

Date

01/05/2024

Pubmed ID

38177221

DOI

10.1038/s41409-023-02178-y

Scopus ID

2-s2.0-85181508004 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

The reduced risk of chronic graft-versus-host-disease (GVHD) with posttransplant cyclophosphamide (ptCy) in the setting of haploidentical related donor and more recently, with HLA-matched related and matched and mismatched unrelated donor allogeneic transplantation has been established. There is, however, paucity of data to show if ptCy impacts chronic GVHD pathogenesis, its phenotype and evolution after HCT regardless of the donor status. We examined the differences in chronic GVHD incidence and presentation in 314 consecutive patients after receiving their first allogeneic transplantation (HCT) using ptCy-based GVHD prophylaxis (ptCy-HCT; n = 120; including 95 with haploidentical related donor) versus conventional calcineurin inhibitor-based prophylaxis (CNI-MUD; n = 194) between 2012 and 2019. The 1-year cumulative incidence of all-grade chronic GVHD and moderate/severe chronic GVHD was 24% and 12%, respectively, after ptCy-HCT and 40% and 23% in the CNI-MUD recipients (p = 0.0003 and 0.007). Multivariable analysis confirmed that use of CNI-based GVHD prophylaxis and peripheral blood stem cell graft as the risk factors for chronic GVHD. The cumulative incidence of visceral (involving ≥1 of the following organs: liver, lungs, gastrointestinal tract, serous membranes) chronic GVHD was significantly higher with CNI-MUD vs. ptCy-HCT (27% vs. 15% at 1 year, p = 0.009). The incidence of moderate/severe visceral chronic GVHD was 20% in CNI-MUD group vs. 7.7% in the ptCy-HCT group at 1 year (p = 0.002). In addition, significantly fewer ptCy-HCT recipients developed severe chronic GVHD in ≥3 organs (0.8%) vs. 8.8% in the CNI-MUD group at 1-year posttransplant (p = 0.004). There was no significant different in relapse, non-relapse mortality, and relapse-free and overall survival between the two groups. Further investigation is needed to confirm that reduced risk and severity of chronic GVHD, less visceral organ distribution with ptCy-HCT leads to improved quality of life.

Author List

Chhabra S, Jerkins JH, Monahan K, Szabo A, Shah NN, Abedin S, Runaas L, Fenske TS, Pasquini MC, Shaw BE, Drobyski WR, Saber W, D'Souza A, Dhakal B, Mohan M, Longo W, Hamadani M

Authors

Sameem Abedin MD Associate Professor in the Medicine department at Medical College of Wisconsin
Anita D'Souza MD Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Meera Mohan MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Lyndsey Runaas MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Calcineurin Inhibitors
Cyclophosphamide
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Methotrexate
Quality of Life
Retrospective Studies
Unrelated Donors