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Myelodysplastic syndromes: moving towards personalized management
Ferrata Storti Foundation
Haematologica 2020 Volume 105(7):1765-1779
Eva Hellström-Lindberg,1 Magnus Tobiasson1 and Peter Greenberg2
1Karolinska Institutet, Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska University Hospital, Stockholm, Sweden and 2Stanford Cancer Institute, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA
ABSTRACT
The myelodysplastic syndromes (MDS) share their origin in the hematopoietic stem cell but have otherwise very heterogeneous biological and genetic characteristics. Clinical features are dominat- ed by cytopenia and a substantial risk for progression to acute myeloid leukemia. According to the World Health Organization, MDS is defined by cytopenia, bone marrow dysplasia and certain karyotypic abnormali- ties. The understanding of disease pathogenesis has undergone major development with the implementation of next-generation sequencing and a closer integration of morphology, cytogenetics and molecular genetics is currently paving the way for improved classification and prognostication. True precision medicine is still in the future for MDS and the develop- ment of novel therapeutic compounds with a propensity to markedly change patients’ outcome lags behind that for many other blood cancers. Treatment of higher-risk MDS is dominated by monotherapy with hypomethylating agents but novel combinations are currently being eval- uated in clinical trials. Agents that stimulate erythropoiesis continue to be first-line treatment for the anemia of lower-risk MDS but luspatercept has shown promise as second-line therapy for sideroblastic MDS and lenalidomide is an established second-line treatment for del(5q) lower-risk MDS. The only potentially curative option for MDS is hematopoietic stem cell transplantation, until recently associated with a relatively high risk of transplant-related mortality and relapse. However, recent studies show increased cure rates due to better tools to target the malignant clone with less toxicity. This review provides a comprehensive overview of the current status of the clinical evaluation, biology and therapeutic interven- tions for this spectrum of disorders.
Definition of myelodysplastic syndromes
The myelodysplastic syndromes (MDS) constitute a spectrum of disorders with variable degrees of cytopenias, morphological dysplasia and risk of progression to acute myeloid leukemia (AML). As such, they provide a clinical model of neoplastic disease capable of progressing from indolent to frankly aggressive. Thus, under- standing the nature of MDS permits analysis of clinical and biological factors involved in maintaining clinical stability and those provoking active tumor progres- sion.
Although MDS comprises heterogeneous subcategories these share a common origin in the hematopoietic stem and progenitor cell compartment.1 The degree of cytopenia partly defines the World Health Organization (WHO) subcategories but certain MDS and subgroups of mixed MDS/myeloproliferative neoplasma (MPN) may present with increased white blood cell, monocyte and platelet counts. Moreover, a diagnosis of MDS can be made in patients with mild or borderline ane- mia if definite morphological or cytogenetic findings are present.1
Besides cytopenia, the main defining feature of MDS is the presence of morpho- logical dysplasia of precursor and mature bone marrow blood cells. A number of dysplastic changes have been defined for each lineage of the bone marrow, as listed in Table 1.
Correspondence:
MAGNUS TOBIASSON
magnus.tobiasson@ki.se
Received: March 23, 2020. Accepted: April 24, 2020. Pre-published: May 21, 2020.
doi:10.3324/haematol.2020.248955
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1765
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