Evidence map›Paper›PMID 41528026›Full record

ArticleBlood2026

The landscape and evolution of clonal hematopoiesis in chronic lymphocytic leukemia.

Othman Al-Sawaf, Benjamin N Locher, Friederike Christen, Raphael Hablesreiter, Anantharamanan Rajamani, Sandra Robrecht, Can Zhang, Anna Maria Fink, Eugen Tausch, Christof Schneider and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Othman Al-SawafDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0001-9895-0570
Benjamin N LocherDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID 0000-0002-8482-4984
Friederike ChristenDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID 0000-0001-8868-2533
Raphael HablesreiterDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Anantharamanan RajamaniDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0001-9439-612X
Sandra RobrechtDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0001-8848-6655
Can ZhangDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Anna Maria FinkDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Eugen TauschDivision of CLL, Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
Christof SchneiderDivision of CLL, Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
Matthias RitgenDepartment of Internal Medicine II (Hematology/Oncology), University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Karl-Anton KreuzerDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Klara KoppDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID 0009-0008-8912-6115
Marie-Elisa MertzDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Coral Fustero-TorreDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Karsten KleoDepartment of Pathology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
John SeymourPeter MacCallum Cancer Center, Melbourne, Australia.ORCID 0000-0003-2188-6835
Piers BlomberyPeter MacCallum Cancer Center, Melbourne, Australia.
Lars BullingerDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Brenda ChylaAbbVie Inc, North Chicago, IL.
Hyun Yong JinGenentech, Inc, South San Francisco, CA.
Yanwen JiangGenentech, Inc, South San Francisco, CA.
Stephan StilgenbauerDivision of CLL, Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
Michael HallekDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0002-7425-4455
Barbara EichhorstDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Petra LangerbeinsDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.ORCID 0000-0002-6654-0304
Kirsten FischerDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
Frederik DammDepartment of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID 0000-0001-5553-1173

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractChronic lymphocytic leukemia (CLL) and clonal hematopoiesis (CH) both commonly occur in older individuals. To characterize CH in CLL, 620 patients were analyzed (CLL12 [ibrutinib vs placebo] and CLL14 [venetoclax-obinutuzumab (Ven-Obi) vs chlorambucil-obinutuzumab (Clb-Obi)]) using error-corrected next-generation sequencing with a variant allele frequency (VAF) threshold of 0.5%. Median follow-up was 76.1 months, and median age was 68 years. CH was detected in 58.2% of patients, most commonly affecting DNMT3A, TET2, TP53, and ASXL1. Longitudinal analysis in CLL14 revealed persistence of the majority of CH clones during follow-up, whereas in more than half of the patients, additional CH mutations were detected. BAX- and U2AF1-mutated CH emerged during Ven-Obi exposure, and PPM1D-mutated CH emerged during Clb-Obi exposure, highlighting treatment gene-specific selection. Clonal fitness analyses revealed accelerated CH clone expansion during therapy, followed by slower growth after treatment. In vitro, genetically modified CD34+ hematopoietic stem/progenitor cells harboring BAX mutations showed enhanced survival and decreased apoptosis. CH was associated with neutropenia, and all patients with Richter transformation (RT; n = 11) had CH. Whole-exome sequencing delineated the contribution of CH mutations in 2 of 4 investigated patients with RT. Large CH clone size (>10% VAF) was independently associated with shorter overall survival with placebo (P = .049) and shorter progression-free survival with Clb-Obi after adjusting for age, immunoglobulin heavy chain variable status, and del(17p). In contrast, CH had no prognostic impact in patients receiving targeted therapies. This study demonstrates the high prevalence of CH, highlights its differential impact across CLL therapies, and underscores its adverse influence on patient outcomes.

Indexed as

Clonal HematopoiesisLeukemia, Lymphocytic, Chronic, B-CellAgedAged, 80 and overFemaleHumansMaleMutation

Identifiers

PMID41528026
PMCPMC13014086

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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.