Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect (Jan 2025, n=20) 3 patients developed severe aGVHD from Donor 1 FMT

[Michael Harrop]

https://www.nature.com/articles/s41467-025-56375-y

Mainly a group from the University of Washington, plus Alexander Khoruts from the University of Minnesota.

Abstract​

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD.

Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes.

Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371

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Donor 1 was a 34-year-old woman with a body mass index (BMI) of 23.5, donor 2 was a 36-year-old man with a BMI of 24.9, and donor 3 was a 40-year-old woman with a BMI of 26.4.

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Absolutely ridiculous that they think these are the important donor factors to list.

0 results for "stool type". And I don't see any information about the pool these 3 donors were chosen from, and why. IE: Were the 3 donors chosen from a pool of 20 applicants? 200 applicants? You chose them based on their age and BMI?

Ah, at the end it's noted:

Donor screening, stool testing for infectious agents, and product manufacturing (Compound MTP101-C; FDA IND #15071) were conducted at the University of Minnesota using Good Manufacturing Practices (cGMP) protocols, as described in our previous trial

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Which is a well-known, poor donor source that keeps being used.

This is infuriating and incompetent because they've already been given the answers. Yet they continued to ignore them and harmed those patients anyway.

They're treating engraftment as "the prize", even though engraftment is not associated with patient outcomes, because this study was another failure and that's the only thing left they have to go on.

They failed, harmed their patients, and they're going to be given more money to keep failing.

the best approach to donor selection remains unknown

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More money being poured down the drain, and more patients being harmed.

The press coverage is all positive and clueless. https://evrimagaci.org/tpg/fecal-microbiota-transplantation-shows-promise-against-graftversushost-disease-161710