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XRCC1 399GG genotype predicts significantly longer overall survival in resistant lymphoma patients treated with Benda-EAM and ASCT

Bone Marrow Transplantation volume 55, pages 818–820 (2020)Cite this article

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Advanced-stage non-Hodgkin (NHL) and Hodgkin lymphoma (HL) are chemotherapy-responsive tumors, but many patients either relapse or never achieve remission after standard treatment. For those patients, high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is considered the golden standard treatment [1]. BEAM (carmustine, etoposide, cytarabine, and melphalan) has been, for a long time, the most commonly used regimen in R/R HL/NHL, given its acceptable efficacy and tolerability. However, due to a sudden shortage of carmustine in recent years, the replacement of carmustine with other agents has become a major challenge worldwide, resulting in the development of new HDT schemes [1, 2]. Starting from in vitro data on lymphoma cell lines, we demonstrated the safety and efficacy of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (Benda-EAM) prior to ASCT in R/R HD and NHL [3, 4]. However, other clinical experiences with these regimen [5,6,7] were not all concordant, with one of them reporting an higher toxicity of Benda-EAM, mainly renal and cardiac [5]. In this light, the identification of biological markers, able to predict response to Benda-EAM, would significantly help the clinical decision making, favouring its use in patients with a high probability of a significant clinical benefit, if compared to other HDT regimens.

Cytotoxic activity of Bendamustine is enhanced by inhibition of the base excision repair (BER) DNA-damage response pathway, suggesting that the BER enzymes play a key role in the repair of DNA damage caused by Bendamustine. We thus analyzed three different genetic variants in BER genes, in order to evaluate their possible prognostic significance in lymphoma patients treated with Benda-EAM/ASCT.

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Acknowledgements

The study was supported in part by AIL Pesaro Onlus.

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  1. These authors contributed equally: Giuseppe Visani, Federica Loscocco and Alessandro Isidori

Authors and Affiliations

  1. Hematology and Stem Cell Transplant Center, Marche Nord Hospital, Pesaro, Italy

    Giuseppe Visani, Federica Loscocco & Alessandro Isidori

  2. Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Urbino, Italy

    Irene Bagaloni, Annamaria Ruzzo & Mauro Magnani

  3. Genetics and Genome Biology, Paediatric Laboratory Medicine (PLM), The Hospital for Sick Children, Toronto, Canada

    Fabio Fuligni

  4. Oncology, Marche Nord Hospital, Pesaro, Italy

    Francesco Graziano

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  1. Giuseppe Visani
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  2. Federica Loscocco
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  4. Annamaria Ruzzo
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  8. Alessandro Isidori
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Correspondence to Giuseppe Visani.

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Visani, G., Loscocco, F., Bagaloni, I. et al. XRCC1 399GG genotype predicts significantly longer overall survival in resistant lymphoma patients treated with Benda-EAM and ASCT. Bone Marrow Transplant 55, 818–820 (2020). https://doi.org/10.1038/s41409-019-0572-7

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