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Circulating low CD4+/CD8+ ratio is associated with poor prognosis in Waldenstrom macroglobulinemia patients

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Abstract

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of β2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.

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Code availability

SPSS ver. 23.0 software (SPSS Inc., Chicago, IL), GraphPad Prism 8

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Acknowledgements

We would like to thank all the members of the hematology department of the First Affiliated Hospital of Nanjing Medical University for the comprehensive support of our efforts to conduct this research and all the patients for completing this work.

Funding

This study was supported by the National Natural Science Foundation of China (81600130, 81770166, 81720108002), Jiangsu Province’s Medical Elite Program (ZDRCA2016022), Project of National Key Clinical Specialty, National Science & Technology Pillar Program (2014BAI09B12), Jiangsu Provincial Special Program of Medical Science (BE2017751) and National Science and Technology Major Project (2018ZX09734007), and Jiangsu Province’s Young Medical Talents Program (QNRC2016683).

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Author notes

  1. Xin Cao and Yi-Lin Kong contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

    Xin Cao, Yi-Lin Kong, Li Wang, Jin-Hua Liang, Yi Xia, Hua-Yuan Zhu, Lei Fan, Jian-Yong Li & Wei Xu

  2. Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China

    Xin Cao, Yi-Lin Kong, Li Wang, Jin-Hua Liang, Yi Xia, Hua-Yuan Zhu, Lei Fan, Jian-Yong Li & Wei Xu

  3. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, China

    Xin Cao, Yi-Lin Kong, Li Wang, Jin-Hua Liang, Yi Xia, Hua-Yuan Zhu, Lei Fan, Jian-Yong Li & Wei Xu

  4. Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 226000, China

    Xin Cao, Sheng-Hua Jiang & Hong Liu

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  1. Xin Cao
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Contributions

C.X. and K.Y.L. created the concept and wrote the paper. W.L. and L.J.H. performed the statistical analysis and analyzed the data. X.Y., Z.H.Y., F.L, and C.X. performed raw data collection. C.X., K.Y.L., J.S.H., L.H., L.J.Y., and X.W. assisted with interpretation of the data and critical revision of the manuscript.

Corresponding author

Correspondence to Wei Xu.

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This research was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University and met the requirements of the institutional, national, and Helsinki declaration.

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Cao, X., Kong, YL., Wang, L. et al. Circulating low CD4+/CD8+ ratio is associated with poor prognosis in Waldenstrom macroglobulinemia patients. Ann Hematol 100, 995–1002 (2021). https://doi.org/10.1007/s00277-021-04474-3

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  • DOI: https://doi.org/10.1007/s00277-021-04474-3

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