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Lymphocyte subpopulation imbalances, bone marrow hematopoiesis and histopathology in rituximab-treated lymphoma patients with late-onset neutropenia

Leukemia volume 22, pages 1446–1449 (2008)Cite this article

Several observations implicate the administration of rituximab in the development of severe late-onset neutropenia (LON) in some patients with lymphoma treated with rituximab±chemotherapy.1, 2, 3, 4, 5 The incidence of LON varies between series; this might be explained, at least in part, by the failure to detect some neutropenic episodes due to their short duration, the relatively long time to onset and the usually uncomplicated course. However, there is a gradual increase in the frequency of rituximab-related LON probably due to the widespread use of rituximab in the standard treatment of lymphomas and also due to the ongoing awareness for this event.

Several groups, including ours, have provided indirect evidence to implicate an immune-mediated mechanism in the pathogenesis of rituximab-associated LON.1, 2, 3, 6 However, published data are mainly based on small series and are often contradictory, perhaps due to the selective evaluation of isolated parameters. Our previous studies suggesting that LON in rituximab-treated lymphoma patients may be associated with T-cell large granular lymphocytic (T-LGL) proliferation1, 2 alluded to the possibility of altered T-cell responses associated with B-cell depletion induced by rituximab. To probe this hypothesis further, in the present study, we performed a detailed immunological and immunohistological study looking for quantitative changes and/or an activated profile of lymphocytes in rituximab-treated patients with LON, focusing on the possibility of T-cell-mediated suppression of bone marrow (BM) hematopoiesis.

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Acknowledgements

We thank Mrs Athina Damianaki, Mrs Claudia Gemetzi and Mrs Helen Koutala, at the University of Crete, and Mrs Varvara Tachynopoulou, at the G. Papanicolaou Hospital, for their valuable technical assistance.

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Authors and Affiliations

  1. Hematology Department and HCT Unit G. Papanikolaou Hospital, Thessaloniki, Greece

    K Stamatopoulos, I Athanasiadou, N Stavroyianni, I Batsis & A Anagnostopoulos

  2. Department of Hematopathology, Evangelismos Hospital, Athens, Greece

    T Papadaki & D Anagnostou

  3. Department of Hematology, University of Crete School of Medicine, Heraklion, Crete, Greece

    C Pontikoglou, K Pyrovolaki & H A Papadaki

  4. Blood Service West of the German Red Cross, Hagen, Germany

    J Bux

  5. Immunology Laboratory, G. Gennimatas Hospital, Athens, Greece

    G Paterakis

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  1. K Stamatopoulos
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  2. T Papadaki
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  3. C Pontikoglou
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  4. I Athanasiadou
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  7. I Batsis
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  8. K Pyrovolaki
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  9. G Paterakis
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  11. A Anagnostopoulos
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  12. H A Papadaki
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Correspondence to K Stamatopoulos.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Stamatopoulos, K., Papadaki, T., Pontikoglou, C. et al. Lymphocyte subpopulation imbalances, bone marrow hematopoiesis and histopathology in rituximab-treated lymphoma patients with late-onset neutropenia. Leukemia 22, 1446–1449 (2008). https://doi.org/10.1038/sj.leu.2405077

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