Data-Driven Harmonization of 2022 Who and ICC Classifications of Myelodysplastic Syndromes/Neoplasms (MDS): A Study By the International Consortium for MDS (icMDS)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.998-998
• Main Authors: Lanino, Luca, Ball, Somedeb, Bewersdorf, Jan Philipp, Marchetti, Monia, Maggioni, Giulia, Travaglino, Erica, Al Ali, Najla H, Fenaux, Pierre, Platzbecker, Uwe, Santini, Valeria, Diez-Campelo, Maria, Singh, Avani M, Jain, Akriti Gupta, Aguirre, Luis E., Tinsley-Vance, Sara M., Schwabkey, Zaker I., Chan, Onyee, Xie, Zhuoer, Brunner, Andrew M., Kuykendall, Andrew T., Bennett, John M., Buckstein, Rena, Bejar, Rafael, Carraway, Hetty E., DeZern, Amy E., Griffiths, Elizabeth A., Halene, Stephanie, Hasserjian, Robert, Lancet, Jeffrey, List, Alan F., Loghavi, Sanam, Odenike, Olatoyosi, Padron, Eric, Patnaik, Mrinal M., Roboz, Gail J., Stahl, Maximilian, Sekeres, Mikkael A., Steensma, David Peter, Savona, Michael R., Taylor, Justin, Xu, Mina, Sweet, Kendra, Sallman, David A, Nimer, Stephen D., Hourigan, Christopher S., Wei, Andrew H., Sauta, Elisabetta, D'Amico, Saverio, Asti, Gianluca, Castellani, Gastone, Borate, Uma M., Sanz, Guillermo, Efficace, Fabio, Gore, Steven D., Kim, Tae Kon, Daver, Naval, Garcia-Manero, Guillermo, Rozman, María, Orfao, Alberto, Wang, Sa A., Foucar, M. Kathy, Germing, Ulrich, Haferlach, Torsten, Scheinberg, Phillip, Miyazaki, Yasushi, Iastrebner, Marcelo, Kulasekararaj, Austin, Cluzeau, Thomas, Kordasti, Shahram, van de Loosdrecht, Arjan A., Ades, Lionel, Zeidan, Amer M., Komrokji, Rami S., Della Porta, Matteo Giovanni
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-186580

Background. The inclusion of gene mutations and chromosomal abnormalities in the 2022 WHO and ICC Classifications of MDS has enhanced diagnostic precision and is expected to improve clinical decision-making process. Although these two systems share similarities, clinically relevant discrepancies still exist and potentially cause inconsistency in their adoption in a clinical setting. In this study on behalf of the International Consortium for MDS (icMDS), we adopted a data-driven approach to provide a harmonization roadmap between the 2022 WHO and ICC classification for MDS. A modified Delphi Process consensus approach is currently ongoing among icMDS experts to finalize a harmonized MDS classification scheme. Methods. We analyzed retrospective international cohorts of patients with a diagnosis of MDS (n=7017) and AML (n=1002) according to WHO 2016 criteria. Hierarchical Dirichlet Processes were applied to define clusters capturing broad dependencies among all gene mutations and cytogenetic abnormalities. To investigate the features of importance and their impact on the clustering process, we employed the SHapley Additive exPlanations approach (SHAP). This allowed to define harmonized labels for each clinical entity. The clinical relevance of the unsupervised clustering was assessed through the analysis of phenotypic features and outcomes among each group. ( Blood 2022;140: 9828-9830) Results. Patients' characteristics are summarized in Table 1. We identified 9 clusters, defined by specific genomic features. The cluster of highest hierarchical importance was characterized by biallelic inactivation of TP53 (biTP53). According to SHAP analysis, bi TP53 was defined as 2 or more TP53 mutations, or 1 mutation with copy number loss or cnLOH. Most patients assigned to bi TP53 cluster had TP53 VAF>10% (77.9%) and complex karyotype (70.1%). Assignment to bi TP53 cluster was irrespective of blast count. Patients with monoallelic TP53 mutation segregated into other clusters. Hierarchically, the second cluster included patients with del(5q). SHAP analysis highlighted 5q deletion alone, or with one other chromosomal abnormality other than -7, and absence of bi TP53, as the most relevant features. Most of these patients had blast counts