Evidence map›Paper›PMID 38283244›Full record

ArticleHeliyon2024

Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn's Disease.

George B McDonald, Ole J B Landsverk, Dermot P B McGovern, Anders Aasebø, Vemund Paulsen, Talin Haritunians, Henrik M Reims, Bernadette M McLaughlin, Timothy Zisman, Dalin Li and 4 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01570348 (Allogeneic Hematopoietic Cell Transplantation for Patients With Treatment-Refractory Crohn's Disease), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01570348 phase2terminatednot on this map

Allogeneic Hematopoietic Cell Transplantation for Patients With Treatment-Refractory Crohn's Disease: A Phase 2 Study

TypeinterventionalSponsorFred Hutchinson Cancer CenterRan2012 to 2019Enrolled2ConditionsCrohn DiseaseArmsAllogeneic Bone Marrow Transplantation, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Mycophenolate Mofetil
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

George B McDonaldClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Ole J B LandsverkDepartment of Pathology, Oslo University Hospital, Oslo, Norway.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Anders AasebøDepartment of Pathology, Oslo University Hospital, Oslo, Norway.
Vemund PaulsenDepartment of Transplantation Medicine, Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Norway.
Talin HarituniansF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Henrik M ReimsDepartment of Pathology, Oslo University Hospital, Oslo, Norway.
Bernadette M McLaughlinClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Timothy ZismanDepartment of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Dalin LiF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Elisabeth T M M ElholmClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Frode L JahnsenDepartment of Pathology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Norway.
George E GeorgesClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Tobias Gedde-DahlDepartment of Hematology, Oslo University Hospital, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Oslo University Hospital · NOCedars-Sinai Medical Center · USUniversity of Washington · USFred Hutch Cancer Center · US

Funding

Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2M
NIDDK NIH HHS U01 DK062413
6 · The paper itself

Abstract

Background & aims: Durable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications. Methods: DNA from patients and their HLA-matched unrelated donors was genotyped and Polygenic Risk Scores calculated. Donor marrow was infused following non-myeloablative conditioning. Patient symptoms and endoscopic findings were documented at intervals after transplant. Results: We screened 807 patients, 143 of whom met eligibility criteria; 2 patients received allografts. Patient 1 had multiple complications and died at day 332 from respiratory failure. Patient 2 had resolution of CD symptoms until day 178 when CD recurred, associated with persistent host chimerism in both peripheral blood and intestinal mucosa. Withdrawal of immune suppression was followed by dominant donor immune chimerism in peripheral blood and resolution of CD findings. Over time, mucosal T-cells became donor-dominant. At 5 years after allografting, Patient 2 remained off all medications but had mild symptoms related to a jejunal stricture that required stricturoplasty at 6 years. At 8 years, she remains stable off medications. Conclusions: The kinetics of immunologic chimerism after allogeneic marrow transplantation for CD patients depends on the intensity of the conditioning regimen and the magnitude of immune suppression. One patient achieved durable improvement of her previously refractory CD only after establishing donor immunologic chimerism in intestinal mucosa. Her course provides proof-of-principal for allografting as a potential treatment for refractory CD, but an immunoablative conditioning regimen should be considered for future studies.(ClinicalTrials.gov, NCT01570348).

Indexed as

Crohn's diseaseMucosal immune chimerismOutcomesPolygenic risk scoreReduced-intensity conditioning

Identifiers

PMID38283244
PMCPMC10818189
OpenAlexW4390563436

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.