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STEM CELL TRANSPLANTATION

Outcome prediction in myelodysplastic neoplasm undergoing hematopoietic cell transplant in the molecular era of IPSS-M

Leukemia volume 37, pages 717–719 (2023)Cite this article

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Outcome of patients with myelodysplastic neoplasms/syndromes (MDS) is closely related to the biology and molecular genetics of the disease as well as its status prior to allogeneic hematopoietic stem cell transplant (HSCT), which remains the only curative option in younger patients [1]. However, early in the management of MDS the ability for general prognostication in terms of HSCT planning is crucial [2], as only 10–15% of all MDS cases are generally eligible for this procedure [3]. Nonetheless, HSCT is potentially burdened by a high rate of complications and a non-negligible risk of associated mortality. Therefore, in the last decade, several groups have attempted to combine both transplant-specific (e.g., age, performance status) and disease-specific (e.g., cytogenetics, bone marrow blasts) risk factors into prognostication scores built to improve prediction of outcome for MDS patients undergoing HSCT [4,5,6].

The introduction of next generation sequencing (NGS) in routine clinical practice has unveiled an abundance of molecular alterations underpinning the tremendous pathomorphological and clinical heterogeneity traditionally ascertained in MDS [7]. Such molecular markers have been found to have well established interactions with disease modifying treatment (DMT), as hypomethylating agents (HMA), and particularly HSCT [1]. For all the above-mentioned reasons, an urgent unmet need of our new molecular era has been the translation of molecular data into empowered prognostications tools, historically relying only on hematological and cytogenetics parameters [8]. The quest for incorporating such information into MDS prognostication culminated in the recent development of the Molecular International Prognostic Scoring System (IPSS-M) [9]. However, a caveat to this score is represented by its best performance in treatment naïve cases, as only 30% of the cohort included in the original study had received DMT and only 9% underwent HSCT, possibly limiting its applicability in a specific transplant setting. Cognizant of the instrumental clinical utility of precisely allocating MDS patients to HSCT, we explored IPSS-M and transplant interactions in a large, real-life cohort of MDS patients, and assessed its incremental prognostication power compared to previous disease- (IPSS-R) and HSCT-specific MDS risk scores.

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Fig. 1: Prognostication of patients with myelodysplastic neoplasm (MDS) undergoing allogeneic hematopoietic stem cell transplant (HSCT) in the molecular era.

Data availability

The datasets used for analysis during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Drs. Elli Papaemmanuil and Elsa Bernard from the Memorial Sloan Kettering Cancer Center for their tremendous contribution in reviewing our results and help in applying the IPSS-M tool in our cohort. We thank grants R01HL118281, R01HL123904, R01HL132071, R35HL135795 and The Leukemia & Lymphoma Society TRP Award 6645-22 (all to JPM), AIRC 5 ×  1000 call “Metastatic disease: the key unmet need in oncology to MYNERVA” project, #21267 (MYeloid NEoplasms Research Venture AIRC), MIUR grant N. 2017WXR7ZT (to MTV) and Ricerca finalizzata grant N.NET-2018-12365935 (all to MTV). This work was supported by a grant from the Edward P. Evans Foundation (to CG).

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Author notes

  1. These authors contributed equally: Carmelo Gurnari, Nico Gagelmann.

  2. These authors jointly supervised this work: Jaroslaw P. Maciejewski, Nicolaus Kröger.

Authors and Affiliations

  1. Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Carmelo Gurnari, Hussein Awada, Danai Dima & Jaroslaw P. Maciejewski

  2. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

    Carmelo Gurnari, Enrico Attardi, Maria Teresa Voso & Raffaella Cerretti

  3. Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Nico Gagelmann, Anita Badbaran, Christine Wolschke & Nicolaus Kröger

  4. Sérvice d’Hématologie Clinique, CHRU de Nancy, Nancy, France

    Simona Pagliuca, Maud D’Aveni-Piney & Marie Thérèse Rubio

  5. CNRS UMR 7365 IMoPa, Biopôle de l’Université de Lorraine, Vandœuvre-lès-Nancy, France

    Simona Pagliuca, Maud D’Aveni-Piney & Marie Thérèse Rubio

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  1. Carmelo Gurnari
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Contributions

CG, NG, JPM and NK generated and conceived the study design, figures, tables and wrote the manuscript; NG performed data analysis. AB, HA, DD, SP, MD’A-P, EA, MTV, RC, CW, MTR, reviewed the clinical data, took part in patient selection and helped editing the manuscript. All authors participated in data interpretation and critical review of the final paper and submission.

Corresponding author

Correspondence to Jaroslaw P. Maciejewski.

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The authors declare no competing interests.

Ethics approval and consent to participate

Ethics approval and patients’ consent to participate to the study was approved by The Institutional Review Board of the participating institutions. All procedures were carried out in accordance with guidelines set forth by the Declaration of Helsinki.

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Written informed consent was obtained from all patients.

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Gurnari, C., Gagelmann, N., Badbaran, A. et al. Outcome prediction in myelodysplastic neoplasm undergoing hematopoietic cell transplant in the molecular era of IPSS-M. Leukemia 37, 717–719 (2023). https://doi.org/10.1038/s41375-023-01820-4

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