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1344 Part X: Malignant Myeloid Diseases Chapter 87: Myelodysplastic Syndromes 1345

patients with multilineage dysplasia and increasing blast percentages Claims-based data suggest that conservatively, at least 30,000 new
are at higher risk of AML transformation and death. However, dedi- cases annually are diagnosed in the United States. It is likely that many
27
cated prognostic models that include features not considered by the additional elderly patients with unexplained cytopenias have MDS, but
WHO classification system are better suited for the estimation of dis- are incompletely evaluated because of severe comorbid conditions lim-
ease risk. Similarly, WHO-defined subtypes do not necessarily share iting life expectancy, clinician oversight of blood test results, or a sense
common pathogenic elements or identify groups of patients most likely of nihilism. Rates of MDS are similar in Western Europe and the United
to respond to particular therapies. Our greater understanding about the States. 28
underlying molecular abnormalities that occur in MDS demonstrate In certain Asian countries and Eastern Europe, MDS is diagnosed
how clinically defined subtypes are genetically very heterogenous. It at a younger age on average than in the United States and Western
is likely that future classification systems will consider somatic muta- Europe. 29–31 The subtypes of MDS that are diagnosed in different regions
tions in MDS driver genes, genes responsible for the clonal outgrowth of the world are also distinct 32,33 ; for instance, for unclear reasons RARS
34
and the eventual development of disease, as a basis for defining disease is rare in Japan compared to the West. Exposure to ionizing radia-
subtypes. tion from the 1945 Hiroshima and Nagasaki atomic bomb explosions
continues to be associated with an increased MDS risk among exposed
Japanese more than 50 years after the events. 35
EPIDEMIOLOGY The median age at MDS diagnosis in the United States is approx-
36
imately 71 years. Onset of MDS before the age of 50 years is uncom-
INCIDENCE BY AGE, SEX, AND OCCUPATION mon, except in cases preceded by irradiation or cytotoxic chemotherapy
The incidence and prevalence of MDS have been difficult to estab- given for another malignancy. 37–39 MDS, as defined by the WHO classifi-
lish, in part because patients are not consistently reported to central cation, occurs in children ages 5 months to 15 years at a rate of approx-
cancer registries. 22–24 Only since 2001 has the United States (U.S.) imately one per 1 million children per year. In contrast to adults, most
National Cancer Institute (NCI) Surveillance, Epidemiology and pediatric cases are oligoblastic myelogenous leukemia (RAEB); clonal
End Results (SEER) database included MDS cases (Fig. 87–1). In sideroblastic anemia is rare. 40,41 A proportion of childhood cases evolve
25
2003, approximately 10,000 new cases were reported to NCI SEER, from inherited predisposing diseases, such as Down syndrome and
most “unclassified” (i.e., not distinguished as lower- or higher-risk). Fanconi anemia, or are associated with germline GATA2 or RUNX1
25
Improved methods of case ascertainment using claims-based data sug- mutations. 42–44 Some cases of Fanconi anemia first present in adulthood
45
gest a high rate of unreported cases and also indicate that MDS is one of as MDS, often in the absence of typical dysmorphology. Dyskeratosis
the most common hematological malignancies. 26 congenita and other telomeropathies can also end in MDS, but many
100

MDS: Incidence by age

Incidence (cases/100,000 population) 10 1 Male

Female

0.1
<40 40–49 50–59 60–69 70–79 80+
Age groups
Figure 87–1. The annual incidence of myelodysplastic syndrome shown by age. There is an exponential (approximately linear on semilogarithmic
plot) increase in incidence from age 40 years on. In persons younger than age 40 years, the incidence is so low that it is aggregated as <40 years. (Data
from the United States National Cancer Institute, Surveillance, Epidemiology, and End-Results Program.)

Kaushansky_chapter 87_p1341-1372.indd 1344 9/21/15 11:04 AM