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Lymphomas

Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease: an independent biological prognostic marker

Leukemia volume 15, pages 458–464 (2001)Cite this article

Abstract

Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie ⩾15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult.

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Acknowledgements

The authors wish to thank the following pathologists for their help in contributing paraffin material: Dr PC de Bruin, Dr N Hofstee, and Dr A Rijlaarsdam. We thank the following hematologists for their help in collecting clinical data: Dr E Balk, Dr J van de Berg, Dr J Mol, Dr SC Riemens, and Dr F De Vries.

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  1. Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    RL ten Berge, JJ Oudejans, DF Dukers & CJLM Meijer

  2. Department of Hematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    GJ Ossenkoppele

  3. Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands

    JWR Meijer

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ten Berge, R., Oudejans, J., Dukers, D. et al. Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease: an independent biological prognostic marker. Leukemia 15, 458–464 (2001). https://doi.org/10.1038/sj.leu.2402045

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