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Stem cell mobilization after bendamustine in indolent lymphomas: a multicenter study on behalf of the Fondazione Italiana Linfomi

Bone Marrow Transplantation volume 55, pages 2350–2353 (2020)Cite this article

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Bendamustine is an alkylating agent with unique chemical structure, including a purine-like benzimidazole ring, and consequent peculiar molecular mechanism of action resulting in high cytotoxic activity [1]. In the last 15 years the association of bendamustine and rituximab (BR) emerged as the worldwide most popular treatment for patients with indolent non-Hodgkin Lymphomas (iNHL), i.e., follicular lymphoma (FL), marginal-zone lymphoma (MZL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). BR if of value either in first-line [2, 3] or in relapsed/refractory (r/r) setting [4]. Autologous stem-cell transplant (ASCT) is a standard option for young fit patients with r/r iNHL [5]. Bendamustine has structural similarities with the purine analog fludarabine, which has been associated with stem-cell toxicity and peripheral blood stem cells (PBSC) mobilization impairment [6]. For these reasons, some caution has emerged in using bendamustine for young iNHL patients who could potentially benefit from ASCT in case of relapse. Preliminary data did not raise major concerns [7,8,9]. However, PBSC mobilization efficiency in patients previously exposed to bendamustine has not been extensively investigated in large multicenter series.

To address this issue, we retrospectively analyzed rates of PBSC mobilization in consecutive patients with iNHL who have previously received bendamustine (in the same or in previous lines of therapy) within 14 Italian centers belonging to the Fondazione Italiana Linfomi network, from 2012 to 2019. The primary objective was the rate of patients achieving a PBSC harvest greater than 2 × 106 CD34+ cells/Kg of body weight at first mobilization attempt (defined as successful). Complete inclusion criteria and end-points of the study, mobilization, collection, and transplant procedures, as well as statistical methods, are described in the Supplementary Online Material.

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Fig. 1: Outline of stem cells mobilization attempts in 50 patients with indolent lymphomas previously treated with bendamustine.

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Acknowledgements

The Varese group was supported by grants of the Fondazione Regionale Ricerca Biomedica (FRRB), Milan, Italy (FRRB project no. 2015-0042, genomic profiling of rare hematologic malignancies, development of personalized medicine strategies, and their implementation into the Rete Ematologica Lombarda clinical network), by Fondazione Matarelli (Milano, Italy) and AIL Varese ONLUS.

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Authors and Affiliations

  1. Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi—ASST Sette Laghi, University of Insubria, Varese, Italy

    Michele Merli, Andrea Ferrario, Benedetta Bianchi, Barbara Mora, Lorenza Bertù & Francesco Passamonti

  2. Hematology Unit, Azienda USL IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Stefano Luminari

  3. Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy

    Stefano Luminari

  4. Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Lucia Farina

  5. Department of Hematology, S. Gerardo University Hospital, Monza, Italy

    Federica Cocito & Silvia Bolis

  6. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Irene Defrancesco & Luca Arcaini

  7. Department of Hematology, Ospedali Riuniti, Ancona, Italy

    Guido Gini

  8. Hematology Unit, Ospedale Guglielmo da Saliceto, Piacenza, Italy

    Annalisa Arcari

  9. Hematology Unit, Department of Medicine—DIMED, University of Padova, Padova, Italy

    Greta Scapinello

  10. Onco-hematology, Hematology Unit, Azienda Ospedaliera of Cosenza, Cosenza, Italy

    Massimo Gentile

  11. Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Maria Goldaniga & Francesca Gaia Rossi

  12. Hematology, IRCCS Ospedale Oncologico Giovanni Paolo II, Bari, Italy

    Giacomo Loseto

  13. Hematology, Azienda Ospedaliera Senese, University of Siena, Siena, Italy

    Emanuele Cencini

  14. Division of Hematology, Ospedale G. Panico, Tricase, Lecce, Italy

    Antonino Greco

  15. Hematology, Ospedale degli Infermi, Rimini, Italy

    Anna Lia Molinari

  16. Apheresis Unit of Immunohematology and Transfusional Service, University Hospital Ospedale di Circolo e Fondazione Macchi—ASST Sette Laghi, Varese, Italy

    Vincenzo Saturni

  17. Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Fabio Bergamini, Nicole Fabbri & Luca Arcaini

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  1. Michele Merli
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Corresponding author

Correspondence to Michele Merli.

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Conflict of interest

SL has reported advisory role for Roche, Celgene, Sandoz, and Gilead Science. LA has reported consultancy or advisory role for Roche, Bayer, Celgene, Sandoz, Verastem and Gilead Sciences, has received research funding from Gilead Sciences and travel expenses from Roche, Celgene, Gilead Sciences and EUSA Pharma and is a member of the speaker’s bureau for Celgene. The remaining authors declare no conflict of interest.

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Merli, M., Luminari, S., Farina, L. et al. Stem cell mobilization after bendamustine in indolent lymphomas: a multicenter study on behalf of the Fondazione Italiana Linfomi. Bone Marrow Transplant 55, 2350–2353 (2020). https://doi.org/10.1038/s41409-020-0967-5

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  • DOI: https://doi.org/10.1038/s41409-020-0967-5

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