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CHRONIC LYMPHOCYTIC LEUKEMIA

Comparison of karyotype scoring guidelines for evaluating karyotype complexity in chronic lymphocytic leukemia

Leukemia volume 38, pages 676–678 (2024)Cite this article

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Karyotype complexity is established by enumerating the number of chromosome abnormalities present in a karyotype. In chronic lymphocytic leukemia (CLL), karyotype complexity, typically defined as ≥3 chromosome abnormalities, is an important prognostic indicator associated with poor outcomes [1]. Additionally, stratifying patients by highly complex karyotypes (≥5 chromosome abnormalities) has shown significantly poorer outcomes compared to patients with 3–4 abnormalities [2]. Further, we have previously shown that complexity is significant as a continuous variable enumerated up to 20 abnormalities [3]. In principle, counting chromosome abnormalities is straightforward; however, in practice it can be nuanced, and the number of abnormalities counted for the same karyotype can differ across laboratories [4]. A lack of standardized rules has resulted in variability with how complexity is evaluated across CLL studies [5]. We and others have previously adapted the international working group on myelodysplastic syndrome cytogenetics (IWGMC) framework [4] for counting chromosome abnormalities for use in CLL [1, 3]. Additionally, a separate set of guidelines were published in the 2020 International System for Human Cytogenomic Nomenclature (ISCN) [6]. These two guidelines differ in several ways, such as how to count unbalanced abnormalities and whether to sum abnormalities across multiple subclones. In a review by Nguyen-Khac et al. the discussion was raised that the differences between these two guidelines can result in discordant complexity assignments for patients [5], which may confound the ability to compare results across clinical trials. We sought to investigate what impact the use of different guidelines for counting chromosome abnormalities may have in CLL correlative studies. Here we evaluated karyotype complexity using both the IWGMC and ISCN guidelines in a previously reported, well-characterized, dataset with long term follow-up of patients with CLL treated with ibrutinib [3].

456 patient karyotypes underwent independent review by two cytogeneticists with enumeration of chromosomes abnormalities up to 20 using each set of guidelines. Discordant scores were discussed to reach consensus. Patients were categorized as not complex (0–2 abnormalities), complex (3–4), or highly complex (≥5). The weighted kappa statistic was used to evaluate agreement between the categories designated by the two guidelines. Progression free survival (PFS) and overall survival (OS) from ibrutinib start were evaluated by the Kaplan-Meier method. Univariable Cox regression model was used to associate the number of abnormalities as a continuous variable or a categorical variable with PFS and OS, and the discrimination power of the models were evaluated by Uno’s concordance statistic.

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Fig. 1: Survival curves of patients placed in discordant karyotype complexity categories depending on guideline used compared to the survival curves of patients with concordant karyotype complexity categorization.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Jondreville L, Krzisch D, Chapiro E, Nguyen-Khac F. The complex karyotype and chronic lymphocytic leukemia: prognostic value and diagnostic recommendations. Am J Hematol. 2020;95:1361–7.

    Article  PubMed  Google Scholar 

  2. Baliakas P, Jeromin S, Iskas M, Puiggros A, Plevova K, Nguyen-Khac F, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood. 2019;133:1205–16. https://doi.org/10.1182/blood-2018-09-873083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kittai AS, Miller C, Goldstein D, Huang Y, Abruzzo LV, Beckwith K, et al. The impact of increasing karyotypic complexity and evolution on survival in patients with CLL treated with ibrutinib. Blood. 2021;138:2372–82.

    Article  CAS  PubMed  Google Scholar 

  4. Chun K, Hagemeijer A, Iqbal A, Slovak ML. Implementation of standardized international karyotype scoring practices is needed to provide uniform and systematic evaluation for patients with myelodysplastic syndrome using IPSS criteria: An International Working Group on MDS Cytogenetics Study. Leuk Res. 2010;34:160–5.

    Article  PubMed  Google Scholar 

  5. Nguyen-Khac F, Bidet A, Daudignon A, Lafage-Pochitaloff M, Ameye G, Bilhou-Nabera C, et al. The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH). Leukemia. 2022;36:1451–66.

    Article  CAS  PubMed  Google Scholar 

  6. McGowan-Jordan J, Hastings RJ, Moore S (eds). ISCN 2020: an International System for Human Cytogenomic Nomenclature (2020). S. Karger AG, Basel, 2020.

  7. Chatzikonstantinou T, Demosthenous C, Baliakas P. Biology and treatment of high-risk CLL: significance of complex karyotype. Front Oncol. 2021;11:788761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nguyen-Khac F, Balogh Z, Chauzeix J, Veronese L, Chapiro E. Cytogenetics in the management of chronic lymphocytic leukemia: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH). Curr Res Transl Med. 2023;71:103410.

    CAS  PubMed  Google Scholar 

  9. Baliakas P, Espinet B, Mellink C, Jarosova M, Athanasiadou A, Ghia P, et al. Cytogenetics in chronic lymphocytic leukemia: ERIC perspectives and recommendations. Hemasphere. 2022;6:e707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, OH, USA

    Matthew R. Avenarius & Cecelia R. Miller

  2. Division of Hematology, The Ohio State University, Columbus, OH, USA

    Ying Huang, Adam S. Kittai, Seema A. Bhat, Kerry A. Rogers, Michael R. Grever & Jennifer A. Woyach

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  1. Matthew R. Avenarius
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  2. Ying Huang
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  7. Jennifer A. Woyach
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  8. Cecelia R. Miller
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Contributions

CRM and MRA designed the study and interpreted data. ASK, SAM, MRG, KAR, and JAW collected data. YH performed statistical analysis. All authors read and approved the manuscript.

Corresponding author

Correspondence to Cecelia R. Miller.

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Competing interests

ASK receives research funding from AstraZeneca and BeiGene, and has consulted for Abbvie, AstraZeneca, Beigene, BMS, Kite/Gilead, Janssen, and LOXO@Lilly, and is on the speaker’s bureau for BeiGene. SAB consulted for Pharmacyclics, Janssen, BeiGene, and AstraZeneca; received an honorarium from OncLive; and received a travel grant from ArQule. KAR receives research funding from Genentech, AbbVie, and Novartis and consults for Pharmacyclics, Janssen, Genentech, Abbvie, AstraZeneca, BeiGene, LOXO@Lilly, and Alpine Immune Science. MRG consults for Astra Zeneca, Pharmacyclics, Ascerta, Axio. Receives research funding from Hairy Cell Leukemia Foundation for Patient Data Registry, travel funding from Hairy Cell Leukemia Foundation and scientific honorarium from University of Pittsburgh. Serves as Board Chair for Scientific Board for Hairy Cell Leukemia Foundation (no reimbursement). JAW receives research funding from Karyopharm Therapeutics, Loxo@Lilly, Schrodinger, AbbVie, and MorphoSys, and consults for ArQule, AstraZeneca, BeiGene, Janssen, Pharmacyclics, Newave, AbbVie, MorphoSys, and Genentech. CRM receives funding from AbbVie. The remaining authors declare no competing interests.

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Avenarius, M.R., Huang, Y., Kittai, A.S. et al. Comparison of karyotype scoring guidelines for evaluating karyotype complexity in chronic lymphocytic leukemia. Leukemia 38, 676–678 (2024). https://doi.org/10.1038/s41375-024-02177-y

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