Evidence map›Paper›PMID 41282159›Full record

ArticleResearch square2025

CAR19 therapy drives expansion of clonal hematopoiesis and associated cytopenias.

Mark P Hamilton, Nick Phillips, Troy Noordenbos, Jan Boegeholz, Takeshi Sugio, Brian J Sworder, Stefan K Alig, Zinaida Good, Joseph G Schroers-Martin, John Tamaresis and 27 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

37 authors.

Mark P HamiltonMD Anderson Cancer Center, Department of Lymphoma and Myeloma, Division of Cancer Medicine, Houston, TX 77030, USA.
Nick PhillipsDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Troy NoordenbosDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jan BoegeholzDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Takeshi SugioDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Brian J SworderDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stefan K AligDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-6825-702X
Zinaida GoodCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-2343-5771
Joseph G Schroers-MartinDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
John TamaresisDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mohammad S EsfahaniDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ying LuDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mari OlsenDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chih Long LiuDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-6577-5427
Zach EhlingerCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Moksha DesaiCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lori MufflyCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-9887-6136
Robert S NegrinCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sally AraiCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-1993-4172
Laura JohnstonCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Robert LowskyCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Everett MeyerCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Andrew RezvaniCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Judith ShizuruCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-3246-4726
Wen-Kai WengCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Parveen ShirazCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-6721-0358
Surbhi SidanaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-3288-7614
Sushma BharadwajCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Melody SmithCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-2702-0381
Saurabh DahiyaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bita SahafCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Matthew J FrankCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0001-6323-4304
Maximilian DiehnDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-2032-0581
David M KurtzDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-6382-4651
David B MiklosCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0003-0717-4305
Ash A AlizadehDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-5153-5625

Funding

TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos, Robert S Negrin · 1989 to 2026
$73.3M
A Genomic Framework for Molecular Risk Prediction & Individualized Lymphoma TherapyR01CA233975 · NCI · STANFORD UNIVERSITY · PI ALIZADEH, ASH ARASH, DIEHN, MAXIMILIAN · 2019 to 2023
$2.8M
NCI NIH HHS P01 CA049605NCI NIH HHS R01 CA233975
6 · The paper itself

Abstract

CD19-directed chimeric antigen receptor T-cell therapy (CAR19) improves survival in patients with relapsed/refractory large B-cell lymphoma (rrLBCL) compared to immunochemotherapy with intent for autologous hematopoietic cell transplantation (HCT). However, major toxicities of CAR19 therapy include prolonged cytopenias, infection, and secondary hematologic malignancies. To investigate the mechanisms underlying these toxicities we studied a cohort of lymphoma patients receiving CAR19. CAR19-treated patients exhibited impaired immune reconstitution and increased infection compared to propensity-matched HCT-treated controls. Bone marrow analysis revealed prolonged post-CAR cytopenias is associated with clonal cytopenias of undetermined significance (CCUS) and is characterized by interferon-mediated inflammation. Despite durable lymphoma remissions, clonal hematopoiesis (CH) commonly expanded following CAR19 infusion and was associated with impaired immune reconstitution and the development of treatment related myeloid malignancy (tMN). The molecular composition and clinical outcomes of post-CAR tMN were comparable to those of post-HCT tMN. Single-cell DNA analysis revealed that most post-CAR CH clones harbored a single independent mutation and that CAR integration into T cells with CH mutations may drive persistence. These findings broadly implicate CH mutation burden and CH expansion in the development of post-CAR cytopenias and malignancies as well as mechanistically suggest these expansions occur in a background of marrow inflammation. Together, our results provide insight into the origins of key CAR19-associated toxicities, including infection and tMN.

Identifiers

PMID41282159
PMCPMC12633523

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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.