The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes

Uma Borate, Antonio Di Stasi

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Myelodysplastic syndromes (MDS) is a heterogeneous group of diseases characterized by an indolent or aggressive course based on age, blood and blast counts and aberrant cytogenetics, within a background of characteristic molecular alterations. While supportive treatment is the mainstay approach for patients with low-risk disease, hypomethylating agents are now the first-line treatment for patients with higher-risk MDS, often used as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT), which remains the only curative option only for about 40-50% of patients. However, considering HSCT-related morbidity and mortality risks it is a suitable therapeutic option only for younger patients (generally up to 70 years of age) without significant comorbidities, and since the prognosis of patients who lose response or progress while on hypomethylating agents is extremely poor alternative strategies are needed. We discuss how to improve current prognostic models like IPSS and IPSS-R by integrating newer somatic mutations and discuss new epigenetic modulators being evaluated as promising new treatment of patients with MDS. Additionally, in order to reduce relapse rate and treatment related morbidity and mortality, we will discuss a newer interesting approach under pre-clinical investigation consisting of chimeric antigen receptor (CAR) modified T-cells redirected against myeloid antigens, as preparatory conditioning to an allogeneic HSCT for MDS and/or acute myeloid leukemia (AML). Newer gene modification strategies are available potentially enabling the specific targeting of myeloid blasts whilst sparing normal hematopoietic cells, with the goal of extending CAR T-cell therapies also to HSCTineligible patients, and they warrant investigations in MDS.

Original languageEnglish (US)
Title of host publicationMyelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis
PublisherNova Science Publishers, Inc.
Pages219-242
Number of pages24
ISBN (Electronic)9781634843300
ISBN (Print)9781634843294
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Epigenomics
Hematopoietic Stem Cell Transplantation
Therapeutics
Morbidity
Antigen Receptors
Mortality
Cell- and Tissue-Based Therapy
T-Cell Antigen Receptor
Acute Myeloid Leukemia
Cytogenetics
Comorbidity
Antigens
Recurrence
Mutation
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Borate, U., & Di Stasi, A. (2016). The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes. In Myelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis (pp. 219-242). Nova Science Publishers, Inc..

The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes. / Borate, Uma; Di Stasi, Antonio.

Myelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis. Nova Science Publishers, Inc., 2016. p. 219-242.

Research output: Chapter in Book/Report/Conference proceedingChapter

Borate, U & Di Stasi, A 2016, The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes. in Myelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis. Nova Science Publishers, Inc., pp. 219-242.
Borate U, Di Stasi A. The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes. In Myelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis. Nova Science Publishers, Inc. 2016. p. 219-242
Borate, Uma ; Di Stasi, Antonio. / The old and the new-integrating prognostic models and mutational advances with epigenetic and cellular therapies for myelodysplastic syndromes. Myelodysplastic Syndromes (MDS): Risk Factors, Treatment and Prognosis. Nova Science Publishers, Inc., 2016. pp. 219-242
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