Fast Facts: Myelodysplastic Syndromes: Determining risk, tailoring therapy, supporting patients

By P. Dyer and M.L. Arellano

Myelodysplastic syndromes (MDS) are a group of clonal myeloid blood disorders that affect older people. As the global population ages, the incidence of these disorders is increasing. As such, healthcare professionals need to be aware of MDS as a possible diagnosis and know how to identify those patients whose condition is most likely to transform to acute myeloid leukemia (AML). Fast Facts: Myelodysplastic Syndromes explains how these disorders are classified, how they present and how prognosis and the risk of transformation to AML are assessed. It also outlines the most appropriate management options for patients of different ages, together with an overview of the latest research under way to further understand MDS and how to treat it. This highly readable resource is the ideal primer on MDS for all members of the multidisciplinary team involved in the care of patients with MDS, including hematologists, hematology trainees, clinical nurse specialists and primary care providers. Table of Contents: • Epidemiology and etiology • Pathogenesis and presentation • Diagnosis and classification • Management • Supporting patients with MDS

• Language: English
• Publisher: S. Karger
• Release date: Feb 12, 2021
• ISBN: 9783318068733

Book preview

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of closely related clonal hematopoietic myeloid disorders that affect older adults. The name is derived from the Greek words ‘μυελός’ or ‘myelos’ meaning marrow, and ‘δυσπλασία’ or ‘dysplasia’ meaning abnormal morphology. MDS are characterized by ineffective hematopoiesis leading to cytopenias and their attendant complications (infection, bleeding and symptomatic anemia), and variable risk of transformation to acute myeloid leukemia (AML). The heterogeneity of MDS relates not only to differences in the morphological appearances of cells, but also to diversity in molecular and cytogenetic abnormalities detectable in the blood and marrow of patients with MDS.

Diagnosis of MDS must be distinguished from that of dysplasia associated with marrow failure syndromes and other clonal disorders, as well as non-clonal, non-malignant causes such as infections, nutritional deficiencies and intoxications. Accurate diagnosis requires excellent morphological evaluation, as well as cytogenetic and molecular data, in the context of peripheral blood cytopenias. Clinical correlation is also important to rule out familial syndromes and non-neoplastic causes of dysplasia.

MDS can be indolent non-progressive disorders, but they can also have an aggressive clinical course with (at times rapid) progression to AML in approximately 15–30% of patients. Various prognostic scoring systems may be used to predict clinical course and time to AML progression, and thus tailor therapy.

The overall 5-year probability of survival for patients with MDS remains poor at approximately 30%. Despite recent improvements in therapies and support, and although several targeted therapies are under investigation, current treatment options remain limited and allogeneic hematopoietic stem cell transplantation is the only potentially curative option for fit young patients with MDS.

This book is designed to provide hematology/oncology nurses, physicians and trainees with concise up-to-date guidance for accurate diagnosis, risk stratification and management of patients with MDS.

1Epidemiology and etiology

Epidemiology

Myelodysplastic syndromes (MDS) predominantly affect older adults (median age of 71–76 years at the time of diagnosis) and affect men more commonly than women. The incidence of MDS increased in 2001–2003 and 2013–2017 from 3.3 to 4.9 per 100 000 persons per year (Figure 1.1).¹ While the rising incidence may be attributed to increased awareness of the disease and improved diagnostic methods, we must not ignore the contribution of an aging population and the number of patients with therapy-related MDS (t-MDS). Figure 1.2 shows the marked increase in patients with MDS after age 70, reaching 54.2 cases per 100 000 in those aged 80 years and over.¹

Although the prevalence of MDS is difficult to estimate because of limitations in tracking, by both registry- and claims-based methods, it is estimated that 87 000 cases are diagnosed globally each year. Approximately 60 000–170 000 people are estimated to be living with MDS in the USA, with 10 000–15 000 new cases diagnosed annually. The European prevalence is estimated to be similar; the European incidence is around four cases per 100 000 persons per year (reaching 40–50 per 100 000 in patients aged ≥ 70 years).²,³

Figure 1.1 Incidence of MDS in the USA by sex (persons per 100 000 per year) in 21 SEER areas (not all US territories represented). Surveillance, Epidemiology, and End Results.¹

Figure 1.2 Incidence of MDS by age and sex. Graph created from SEER data.¹

Etiology

Risk factors include age, male sex, prior radiation therapy and/or chemotherapy, exposure to organic solvents such as benzene, smoking and obesity. However, the vast majority (80%) of cases are idiopathic in nature (de novo MDS).

Previous exposure to chemotherapy and/or radiation is noted in 10–15% of patients (t-MDS or treatment-related acute myeloid leukemia [t-AML]). Time to development depends on the type and dose of exposure.

Alkylating agents, such as cyclophosphamide, chlorambucil, nitrosoureas, mechlorethamine and melphalan, have a latency of 6–7 years.⁴

Topoisomerase-II inhibitors, such as etoposide and doxorubicin, have shorter latency (< 2 years), and more frequently present with t-AML. Accelerated transition from t-MDS to t-AML has been postulated in patients treated with topoisomerase-II inhibitors.⁵

Mutational patterns of patients with t-MDS differ from those with de novo MDS, with a higher frequency of complex karyotype and p53 mutations.⁶ Interestingly, the genetic features and clinical behaviors of MDS diagnosed in patients previously treated with radiation therapy alone differ from those in patients previously exposed to a combination of radiation and chemotherapy. The former tend to have more favorable cytogenetic lesions, lower-risk International Prognostic Scoring System (IPSS) scores and outcomes more similar to de novo MDS, while the latter have more adverse risk cytogenetics, higher-risk IPSS