If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell malignancies with significant morbidity and high mortality. The incidence of MDS increases markedly with age, and the disease is most prevalent in individuals who are white and male. It is conservatively estimated that >10,000 new cases of MDS occur in the United States annually, and that ≥60,000 individuals with MDS currently reside in the country. With an aging population and an improving awareness of the disease, the documented disease burden is expected to escalate in the near future. Recent studies have identified new or inconsistent etiologic factors that warrant further research. Given the poor survival of individuals with MDS, it is important to identify prognostic factors to better risk-stratify patients for more effective treatment. The relevance of different comorbidities to MDS prognosis and the potential interaction between various comorbidities represents an interesting area of research.
For many years, myelodysplastic syndromes (MDS) were considered preleukemic conditions owing to a relatively high rate of disease progression to acute myeloid leukemia (AML). More recent research has suggested that MDS has a clonal nature. In 2000, the World Health Organization (WHO) changed the behavior code for MDS in the International Classification of Diseases for Oncology (ICD-O) from 1 (i.e., uncertain whether benign or malignant) to 3 (i.e., malignant).
Fritz A. Percy C. Jack A. Shanmugarathan S. Sobin L. Parkin D.M. Whelan S. International Classification of Diseases for Oncology (ICD-O). 3rd ed. World Health Organization,
Geneva2000
Subsequently, in 2001 MDS became reportable to population-based cancer registries, such as the Surveillance, Epidemiology, and End Results (SEER) Program led by the US National Cancer Institute (NCI), which made it possible to obtain population-level data on MDS morbidity and mortality. The addition of MDS to cancer reporting represents an important step toward better describing the morbidity and mortality of the disease.
The addition of MDS to cancer reporting represents an important step toward better describing the morbidity and mortality of the disease.
Incidence and Prevalence
Incidence is defined as the rate at which new cases of a disease or condition occur. In 1995, the number of incident MDS cases in the United States was estimated to be around 1,500 annually.
Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs.
A recent study based on Medicare claims reported that approximately 45,000 new cases of MDS were diagnosed in individuals aged ≥65 years in the United States in 2003.
This was likely an overestimation because the International Classification of Diseases, Ninth Revision (ICD-9) code used in this study to ascertain patients with MDS from Medicare claims was not specific to MDS, and included other hematopoietic conditions.
Exactly how many incident cases of MDS occur in the United States is not completely resolved. Population-based cancer registries, such as the SEER Program, are usually the authoritative source of information for cancer morbidity and mortality in the country. As with the surveillance of many other diseases, the completeness of case ascertainment was a concern shortly after MDS became a reportable condition. As observed with the SEER Program data, the age-adjusted incidence rate of MDS was 3.6 cases per 100,000 persons per year in the first year that MDS was reportable (2001), had increased to 3.8 cases per 100,000 persons per year in the following year (2002), and ranged from 4.1 to 4.6 cases per 100,000 persons per year during 2003 to 2008.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
This suggests that MDS case ascertainment might have been incomplete in the first 2 years of reporting, but has improved and become stable over time. A diagnosis of MDS can be made in the outpatient setting with bone marrow specimens reviewed by pathology laboratories, without visiting a hospital. If a cancer registry has incomplete coverage of pathology laboratories, a diagnosis of MDS may be missed. There are regional variations in the incidence rate of MDS,
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
Approximately 86% of patients with MDS were aged ≥60 years at the time of their diagnosis (median age, 76 years), and only 6% of cases were diagnosed in those aged ≤50 years.
With an aging population, an increasing rate of secondary MDS, improved awareness of the disease, and more thorough clinical workups, it is likely that the number of new patients diagnosed with MDS each year will increase in the future. Indeed, emerging evidence suggests that MDS is more common than previously believed.
FigureIncidence rate of myelodysplastic syndromes (MDS) in different age groups in the United States (2001 to 2008).
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
Prevalence reflects the percentage of a population that lives with a disease. Clinically, prevalence is sometimes used interchangeably with the total number of patients who live with a disease, but strictly speaking prevalence is a percentage. Estimates of the number of people living with MDS are elusive. Preliminary data from Germany reveal an MDS prevalence of 20.7 cases per 100,000 people. Applying a similar prevalence to the population of the United States would result in an estimated 60,000 patients with MDS.
In the noninstitutionalized United States population assessed in the 1988 to 1994 third National Health and Nutrition Examination Survey (NHANES III), 11.0% of men and 10.2% of women aged ≥65 years had anemia and a third of those individuals were considered to have unexplained anemia.
As 17.2% of patients with unexplained anemia have disease characteristics consistent with a diagnosis of MDS (i.e., macrocytosis, neutropenia, thrombocytopenia), MDS may actually be the underlying disease in some of these patients.
This suggests that MDS may not be as rare a disease in the United States as previously thought. As the cancer registry-based incidence of MDS is similar to that of AML and the survival rate of patients with MDS is considerably higher than compared with patients with AML, the prevalence of MDS is far greater than that of AML. Although the knowledge of MDS is increasing since it became reportable in SEER in 2001, compared with AML and many other types of hematologic malignancies MDS remains understudied and underserved from an epidemiologic perspective.
Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs.
Patients with MDS who have a history of cancer treatment are considered to have “secondary” or “therapy-related” MDS, and they tend to have a much poorer prognosis. The WHO recommends that these cases be grouped with AML rather than with “Other” MDS.
; however, the findings are far from consistent. The relation between alcohol consumption and MDS has been assessed in several studies with conflicting results. Although alcohol consumption did not appear to affect the risk of MDS in some studies,
Ido and colleagues reported a significant association between alcohol use and MDS (odds ratio, 2.15; 95% confidence interval [CI], 1.12 to 4.16) as well as a dose-response relation.
In contrast, a recent case-control study by Strom and associates found that the moderate consumption of wine was associated with a significantly decreased risk of MDS.
Compared with individuals with a BMI <25.0 (i.e., normal weight), the relative risks for those with a BMI of 25.0 to 29.9 (i.e., overweight) and ≥30.0 (i.e., obese) were 1.15 (95% CI, 0.81 to 1.64) and 2.18 (95% CI, 1.51 to 3.17), respectively. This association was not affected by physical activity, smoking status, or alcohol intake, and there appeared to be a trend.
The findings were derived from a prospective cohort study with more than a half million participants, which was the first and only cohort study to evaluate MDS etiology.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
Previous studies have identified several prognostic factors, including age, sex, transfusion dependence, MDS subtype, bone marrow blast percentage, number of cytopenias, and cytogenetics.
The latter 3 disease features represent major factors determining outcomes for patients with MDS in prognostic models such as the International Prognostic Scoring System (IPSS).
as significant and independent predictors of MDS survival. In terms of comorbidities, different diseases or conditions appeared to have a varying impact on the prognosis of MDS. For example, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) were associated with shortened survival, whereas diabetes and cerebrovascular diseases did not alter the prognosis of patients with MDS.
These findings were not surprising because CHF and COPD can be severely exacerbated by anemia and infection, both hallmarks of MDS. Also, if a patient with MDS undergoes disease transformation to AML the presence of CHF can limit the potential for administration of anthracyclines, which are among the primary chemotherapeutic agents for leukemia, because of their cardiac toxicity. Given that a “typical” elderly oncology patient has ≥3 comorbid conditions,
it is necessary to assess the relevance to MDS prognosis of different common conditions as well as the potential interaction between different conditions. Furthermore, it may be important for clinicians to incorporate comorbidities into the risk stratification of patients with MDS when evaluating treatment options.
Summary
The MDS are a group of understudied hematologic disorders, and MDS may be the underlying condition affecting some elderly patients with unexplained anemia. Thus, the classification of MDS as a malignancy, the addition of MDS to cancer reporting, and the approval of new drugs for the treatment of MDS are all welcome developments in MDS research. With the current demographic trend, increasing disease morbidity (both incidence and prevalence) is expected in the near future. More research is required to elucidate the etiology of MDS and to assess the role of a comprehensive list of factors in the prognosis of MDS. The ultimate goal is the development of preventive measures to reduce disease occurrence and to treat patients more effectively in order to reduce mortality and improve quality of life.
Author Disclosures
The author of this article has disclosed the following industry relationships:
Xiaomei Ma, PhD, reports no relationships to disclose with any manufacturer of a product or device discussed in this supplement.
Acknowledgments
The author received editorial support provided by Nikki Moreland of Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. The author is fully responsible for content and editorial decisions for this manuscript. The author’s previous work cited in this article was supported in part by two grants from the National Cancer Institute (R21 CA131927 and K07 CA119108).
References
Fritz A. Percy C. Jack A. Shanmugarathan S. Sobin L. Parkin D.M. Whelan S. International Classification of Diseases for Oncology (ICD-O). 3rd ed. World Health Organization,
Geneva2000
Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 17 Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, National Cancer Institute, Division of Cancer Control & Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2011, based on the November 2010 submission.
00338-5&id=gr1.jpg){kind=link}