Diagnosis and Treatment of Myelodysplastic Syndromes

Abstract

he myelodysplastic neoplasms (MDS), formerly known as myelodysplastic syndromes, are a group of cancers characterized by failure of bone marrow stem cells to mature into normal-functioning blood cells. MDS are characterized by reduced numbers of peripheral blood cells, an increased risk of acute myeloid leukemia transformation, and reduced survival, with a 5-year survival rate of approximately 37%. 1,2 The yearly incidence of MDS is approximately 4 per 100 000 people. 3 MDS are more common in men (with yearly incidence rates of approxi-mately 5.4 per 100 000 vs 2.9 per 100 000 for women) and are more common among people who are White compared with people who are Asian/Pacific Islander (4.0 per 100 000), Black (2.7 per 100 000), or Hispanic (2.9 per 100 000), and among people who are older. 3 The median age of diagnosis is approximately 70 years, and the yearly incidence rate increases to 25 per 100 000 in people aged 65 years and older. 3 Older age is associated with clonal hematopoiesis of indeterminate potential, which is considered a precursor to MDS. 4 Additional risk factors IMPORTANCE Myelodysplastic neoplasms (MDS), formerly known as myelodysplastic syndromes, are clonal hematopoietic malignancies that cause morphologic bone marrow dysplasia along with anemia, neutropenia, or thrombocytopenia. MDS are associated with an increased risk of acute myeloid leukemia (AML). The yearly incidence of MDS is approximately 4 per 100 000 people in the United States and is higher among patients with advanced age.OBSERVATIONS MDS are characterized by reduced numbers of peripheral blood cells, an increased risk of acute myeloid leukemia transformation, and reduced survival. The median age at diagnosis is approximately 70 years, and the yearly incidence rate increases to 25 per 100 000 in people aged 65 years and older. Risk factors associated with MDS include older age and prior exposures to toxins such as chemotherapy or radiation therapy. MDS are more common in men compared with women (with yearly incidence rates of approximately 5.4 vs 2.9 per 100 000). MDS typically has an insidious presentation, consisting of signs and symptoms associated with anemia, thrombocytopenia, and neutropenia. MDS can be categorized into subtypes that are associated with lower or higher risk for acute myeloid leukemia transformation and that help with therapy selection. Patients with lower-risk MDS have a median survival of approximately 3 to 10 years, whereas patients with higher-risk disease have a median survival of less than 3 years. Therapy for lower-risk MDS is selected based on whether the primary clinical characteristic is anemia, thrombocytopenia, or neutropenia. Management focuses on treating symptoms and reducing the number of required transfusions in patients with low-risk disease. For patients with lower-risk MDS, erythropoiesis stimulating agents, such as recombinant humanized erythropoietin or the longer-acting erythropoietin, darbepoetin alfa, can improve anemia in 15% to 40% of patients for a median of 8 to 23 months. For th...

A treatment-refractory and aggressive MDS-MLD with multiple highly complex chromosome 5 intrachromosomal rearrangements: a case report

“…Deletions of 5q are the only genetic abnormalities that truly de ne a speci c MDS subtype [15,16]. Most patients with isolated del(5q) MDS can remain in a chronic stable condition for many years [2,3], with a majority of patients dying from complications of MDS without transforming to AML [4,5]. Therefore, some patients require tailored MDS-speci c treatment(s).…”

“…Myelodysplastic neoplasms (MDS), formerly known as myelodysplastic syndromes comprise a group of clonal hematopoietic stem cell malignancies involving one or more myeloid lineages that result in abnormal cellular maturation [1,2]. Clonal chromosomal abnormalities are observed in approximately 50% of de novo and up to 90% of therapy related MDS patients [3,4,5].…”

“…Monoallelic interstitial or terminal deletions of the long arm of chromosome 5 [del(5q)] is a recurrent cytogenetic abnormality common to a category of MDS sometimes referred to as 5q-syndrome [4,5]. This category of MDS has a relatively favorable prognosis with low risk of progression to AML as compared to other types of MDS [2,3].…”

A treatment-refractory aggressive MDS-MLD with multiple highly complex chromosome 5 intrachromosomal rearrangements: a case report

“…Deletions of 5q are the only genetic abnormalities that truly define a specific MDS subtype [ 16 , 17 ]. Most patients with isolated del(5q) MDS can remain in a chronic stable condition for many years [ 2 , 3 ], with a majority of patients dying from complications of MDS without transforming to AML [ 4 , 5 ]. Therefore, some patients require tailored MDS-specific treatment(s).…”

“…Clinical data and literature suggest most patients with 5q- syndrome (as the sole change) have a good prognosis [ 2 ]. However, a subset of MDS patients with 5q deletion may undergo clonal evolution resulting in the formation of complex karyotypes [ 10 ].…”