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Novel Strategies to Manage Cytopenia in Low-Risk MDS

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Pathogenesis and Treatment of Leukemia

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Abstract

Lower-risk myelodysplastic syndromes (LR MDS) constitute the majority of cases and their clinical manifestation is determined by cytopenias. Improvements in diagnosis and prognostic stratification have been obtained with the application of NGS and advanced flow cytometry. Due to this enhanced characterization, LR MDS may be treated more efficiently with several treatment options currently available. Anemia is indeed the most frequent cytopenia, present in >90% of cases, and there are effective therapies to alleviate it. Erythropoiesis-stimulating agents (ESAs) are known to be active in the majority of cases, but at present, new experimental agents are under evaluation for patients who relapse after ESAs or are refractory to them. Empirically, agents with different mode of action are investigated, like imetelstat and roxadustat. Luspatercept, a TGF-beta pathway inhibitor restoring transfusion independence in nearly half of MDS with ring sideroblasts, has been recently approved. Lenalidomide is the treatment of choice in MDS del5q; in this therapeutic setting, determination of mutant TP53 and its allele burden is crucial. Although chronic transfusions may still be a treatment of LR MDS, optimization of iron chelation therapy has been demonstrated to decrease organ damage and prolong survival.

Thrombocytopenia, although present in around 30% of LR MDS, impacts on overall survival, but there is no standard treatment for it. Thrombomimetic agents are active in decreasing bleeding episodes and increasing platelet number, but have not been approved, most probably because of some concerns linked to their stimulating activity on early hematopoietic progenitors.

Finally, isolated neutropenia is rare in LR MDS. There is no evidence in favor of the use of myeloid-stimulating factors in preventive therapy. Some LR MDS present anemia associated with thrombocytopenia or neutropenia. In these cases, the use of hypomethylating agents, especially the oral formulations, may be considered, with the caveat of inevitable myelosuppression.

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Authors and Affiliations

  1. MDS Unit, Department of Experimental and Clinical Medicine, Hematology, University of Florence, Firenze, Italy

    Valeria Santini

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Correspondence to Valeria Santini .

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  1. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Harinder Gill

  2. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Yok-Lam Kwong

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Santini, V. (2023). Novel Strategies to Manage Cytopenia in Low-Risk MDS. In: Gill, H., Kwong, YL. (eds) Pathogenesis and Treatment of Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-99-3810-0_33

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  • DOI: https://doi.org/10.1007/978-981-99-3810-0_33

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