Evidence map›Paper›PMID 42010448›Full record

ArticleJournal of hematology & oncology2026

Uncoupling toxicity from efficacy in donor selection for allogeneic hematopoietic cell transplantation: a retrospective cohort study using double machine learning.

Rohtesh S Mehta, Yosra M Aljawai, Warren Fingrut, Portia Smallbone, Gabriela Rondon, Amanda Olson, Betul Oran, Partow Kebriaei, Richard E Champlin, Elizabeth J Shpall

Abstract read
In one paragraph

Article in Journal of hematology & oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  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

10 authors.

Rohtesh S MehtaDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA. rmehta1@mdanderson.org.
Yosra M AljawaiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Warren FingrutDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Portia SmallboneDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Gabriela RondonDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Amanda OlsonDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Betul OranDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Partow KebriaeiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Richard E ChamplinDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.
Elizabeth J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0423, Houston, TX, 77030, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Haploidentical hematopoietic cell transplantation (HCT) offers potent graft-versus-tumor effects but is historically limited by higher non-relapse mortality (NRM) compared to matched unrelated (MUD) or related donors (MRD). To algorithmically decouple the competing risks of NRM and relapse, we analyzed 1,713 adult patients (MD Anderson discovery cohort) and 6,829 patients (registry replication cohorts) using a double machine-learning framework of Causal Survival Forests to estimate individualized treatment effects, while Random Survival Forests defined absolute prognostic risk. We found biological uncoupling of relapse and NRM: relapse was driven by disease biology, while NRM was governed by physiological reserve. Specifically, cardiovascular or cerebrovascular comorbidities acted as selective amplifiers of haploidentical toxicity-a "vascular penalty" that doubled mortality risk in the bootstrapped model (sub-distribution hazard ratio 2.09, 95% confidence interval 1.26-3.35). We developed a 3-factor nomogram (recipient age, vascular comorbidity, B-leader matching status) to identify an "Optimized Haploidentical" phenotype. Exploratory multivariable modeling suggested MUD consistently maximized predicted disease-free survival across all subgroups. Among haploidentical versus MRD comparisons, B-leader mismatch appeared to favor MRD across ages, while B-leader matched haploidentical donors in older patients (≥ 60 years) modeled near-equivalent DFS to MRD, representing a hypothesis-generating "zone of equivalence" requiring prospective validation.

Indexed as

Donor SelectionHematopoietic Stem Cell TransplantationMachine LearningAdultFemaleHumansMaleMiddle AgedRetrospective StudiesTransplantation, HomologousDisease-free survivalHaploidenticalHCTHematopoietic cell transplantationMatched related donorMatched unrelated donorNon-relapse mortalityNRMPost-transplantation cyclophosphamidePTCyRelapse

Identifiers

PMID42010448
PMCPMC13094119

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.