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Microbiota dysbiosis after high-dose melphalan and autologous hematopoietic cell transplantation in multiple myeloma

Bone Marrow Transplantation volume 58, pages 1275–1278 (2023)Cite this article

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The impact of gut microbiota composition on patients’ outcomes after allogeneic hematopoietic cell transplantation (alloHCT) is now well established. In particular, a large study including patients treated in four centers across three continents confirms that loss of gut microbiota diversity at engraftment is associated with a lower overall survival (OS) [1]. Similarly, the role of the gut microbiota on patients’ outcomes after autologous (auto) HCT was recently investigated in a cohort of 534 patients with lymphoma, multiple myeloma (MM) and amyloidosis [2]. They found that an above median fecal intestinal diversity in the peri-engraftment period was associated with decreased risk of death or progression, adjusting for disease and disease status. Nevertheless, little data are available regarding the durability of microbiota changes after autoHCT. It was recently shown that after induction chemotherapy for acute myeloid leukemia and despite major reductions in antibiotic pressure after hospital discharge, the trajectory of microbiota recovery yielded new communities that were highly dissimilar to baseline [3]. Whether the microbiota follows a similar pattern after autoHCT remains to be confirmed. With this background we performed a study to evaluate gut microbiota composition up to day 90 (D90) after high- dose melphalan (HDM) and autoHCT for MM.

This retrospective analysis included 23 adult patients who underwent HDM and autoHCT for MM between May 2016 and October 2018 in our institution (Saint-Antoine University Hospital, Paris, France) and who had at least two evaluable fecal samples, one collected before HDM and the second after autoHCT. Fecal sample collection was planned before HDM (D-2 sample, D0 being the day of autoHCT) and then at day 7 (D7 sample), at neutrophil recovery (D14 sample), at day 60 (D60), and at D90. Infection prophylaxis, monitoring, and supportive care, stool collection, DNA extraction, 16S DNA sequencing, 16S sequence analysis, and statistical analyses are described in the Supplementary Methods. Patient and transplant characteristics are detailed in Table 1. Written informed consent was obtained from each patient. The study was approved by the local institutional review board.

Table 1 Study population and transplant characteristics.
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Fig. 1: Gut microbiota diversity during transplantation period.

References

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Acknowledgements

The authors acknowledge the « af3m, Association Française des Malades du Myélome Multiple » and the « IFM, Intergroupe Francophone du Myélome » for their support. The authors acknowledge the “Tumorothèque” of the Clinical Haematology Department at Saint-Antoine hospital for logistical support for handling of samples. The authors acknowledge the Association for Training, Education and Research in Hematology, Immunology and Transplantation for the generous and continuous support of the research work. We thank our nursing staff for offering the best care to our patients.

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Authors and Affiliations

  1. Sorbonne Université, APHP, Hôpital Saint Antoine, Service d’Hématologie Clinique et de Thérapie cellulaire, Paris, France

    Florent Malard, Giorgia Battipaglia, Zoe van de Wyngaert, Agnes Bonnin, Rémy Duléry, Anne Banet, Nicolas Stocker, Laure Ricard, Eolia Brissot & Mohamad Mohty

  2. INSERM, Centre de Recherche Saint-Antoine (CRSA), F-75012, Paris, France

    Florent Malard, Giorgia Battipaglia, Béatrice Gaugler, Lama Siblany, Zoe van de Wyngaert, Agnes Bonnin, Rémy Duléry, Anne Banet, Nicolas Stocker, Laure Ricard, Eolia Brissot & Mohamad Mohty

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  1. Florent Malard
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Contributions

FM designed the study, recruited patients, performed experimental work, collected, assembled and analyzed data, and wrote and revised the manuscript. GB recruited patients, collected and assembled data, and helped write the manuscript. BG, LS, NS and LR, performed experimental work, collected, assembled, analyzed data, and helped write the manuscript. ZW, ABo, RD, ABa and EB recruited patients, collected data and helped write the manuscript. MM designed the study, supervised research, analyzed data and helped write the manuscript.

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Correspondence to Florent Malard.

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Competing interests

FM reports lecture honoraria from, Therakos/Mallinckrodt, Janssen, Sanofi, JAZZ Pharmaceuticals, Gilead, Novartis, and Bristol Myers Squibb, all outside the submitted work. MM reports grants and lecture honoraria from Janssen, Sanofi, Maat Pharma and JAZZ Pharmaceuticals, lecture honoraria from Celgene, Amgen, BMS, Takeda, and Pfizer, grants from Roche, all outside the submitted work. The other authors declare no competing financial interests. RD reports research funding from Ligue contre le Cancer, Arthur Sachs, Monahan Foundation, Servier Foundation, Philippe Foundation, DCP AP-HP, honoraria from Novartis and Takeda, non-financial support from Kite Pharma/Gilead, all outside the submitted work.

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Malard, F., Battipaglia, G., Gaugler, B. et al. Microbiota dysbiosis after high-dose melphalan and autologous hematopoietic cell transplantation in multiple myeloma. Bone Marrow Transplant 58, 1275–1278 (2023). https://doi.org/10.1038/s41409-023-02078-1

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