Differential effects of two common GVHD prophylaxis regimens on the gut microbiome: Results from the BMT CTN 1801 study

作者：Jakob Wirbel, Wael Saber, Michael J. Martens, Jonathan U. Peled, Tessa M Andermann, Teng Fei, Erin F. Brooks, Boryana Doyle, Nathan B. Pincus, Robert R. Jenq, Merav Bar, Javier Bolaños-Meade, Brandi Bratrude, Saurabh Chhabra, Sung Won Choi, William Clark, Suman R. Das, Hany Elmariah, Mahasweta Gooptu, Shernan G. Holtan, Richard J. Jones, Levine Jp, Brent R Logan, Monzr M Al Malki, Hemant S. Murthy, Armin Rashidi, Andrew R. Rezvani, Marcie L. Riches, Lyndsey Runaas, Karamjeet Sandhu, Ashley Spahn, Anthony D. Sung, Marcel R.M. van den Brink, MM Horowitz, Mehdi Hamadani, Leslie S. Kean, Miguel-Angel Perales, Ami S. Bhatt · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.02.19.706769 · 被引用次数：1 · 研究领域：Gut microbiota and health、Neutropenia and Cancer Infections、Clostridium difficile and Clostridium perfringens research

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14–28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable acr...