Burden of Myelodysplastic Syndromes: A Literature Review of Epidemiological and Humanistic Aspects

Myelodysplastic syndromes (MDS) are a group of clonal neoplastic bone marrow disorders characterized by ineffective hematopoiesis and cytopenia [1]. Given the increasing incidence of MDS in aging populations and its chronic disease burden, understanding its epidemiological trends and humanistic burden is crucial. Despite several reviews that have examined epidemiological or humanistic burden of MD, existing literature is often limited in scope, focusing on specific subgroups, for example, higher-risk MDS, or single geographic regions. Furthermore, heterogeneous study methodologies have led to inconsistent estimates of MDS incidence, prevalence, and mortality, complicating comparisons across populations. The aim of this study was to conduct a scoping literature review to summarize both the epidemiological and humanistic burden of MDS.

A systematic search was conducted to understand the epidemiological, humanistic, and economic burden of MDS. The search was undertaken from inception to July 13, 2021 in Embase and Medline. A detailed search strategy is presented in Table S1. Bibliographic searches of systematic reviews identified during the screening were conducted to validate the search strategy and identify any additional publications that were not retrieved through the original search. Studies were included if they (1) included patients with MDS and assessed epidemiologic (i.e., prevalence, incidence or mortality) or humanistic (i.e., patient-reported outcome using either a generic or disease-specific instrument) outcomes; (2) had a sample of more than 100, and (3) were published in English. Systematic reviews were excluded, but if relevant, their reference lists were cross-referenced. Study selection involved two phases: an initial screening based on title and abstract followed by a full-text review. Both phases of screening were performed by two reviewers independently and in duplicate. Any discrepancies were solved by discussion between the two reviewers or consulting a third reviewer when necessary. A study mapping process was conducted to match publications reporting on the same study. For included studies, information on study and patient characteristics, and outcomes of interest were extracted by two reviewers independently using a standardized data extraction form. Discrepancies were reconciled by discussion between the two reviewers or in consultation with a third reviewer when necessary.

The study employed descriptive analyses to summarize the epidemiological and HRQoL outcomes in patients with MDS. The descriptive statistics included age-standardized incidence rate (ASIR), prevalence, and survival rates. Data were organized in Excel and visualized with R using distribution plots and trend graphs.

A total of 63 papers (56 studies) reported on the epidemiological burden of MDS and 57 papers (46 studies) on the HRQoL burden of MDS. The selection process is summarized in Figure S1. Details on studies reporting epidemiological and HRQoL outcomes are provided in Tables S2 and S3, respectively.

As shown in Table 1, among the 56 studies reporting epidemiological outcomes, 40 (71.4%) were database analyses, 11 (19.6%) retrospective cohort studies, and 5 (8.9%) prospective cohort studies. Studies were conducted across diverse regions: 30 (53%) studies in Europe, 13 (23%) in North America, 7 (13%) in Asia, and the rest in Oceania, South America, and Africa. Median age of patients at the diagnosis of MDS ranged from 62 to 79 years. The adult ASIR, reported in 16 studies for 12 countries, varied from 0.98 in Korea to 11.5 per 100,000 in Argentina (Figure S2a. ASIR was higher in males (1.0–7.9 per 100,000) than in females (0.5–6.2 per 100,000) (Figure S2b). Four studies showed ASIR rising with age, from 0.3–0.9 per 100,000 in those under 50 to 28.5–84.4 per 100,000 in patients over 80 (Figure S2c). France and the United Kingdom reported ASIRs of 0.03 and 0.04 per 100,000 for pediatric patients. Crude prevalence ranged from 6.2–12.0 per 100,000 in registries to 155 per 100,000 in claims data (Table S2). One-year survival ranged from 66%–69%, while 3-year and 5-year survival rates exhibited ranges of 42% to 45%, and 27% to 46%, respectively. Both 3-year and 5-year survival rates declined as age increased. Age-standardized mortality rates were 1.14–1.63 per 100,000, with crude mortality from 0.15 for very low-risk MDS to 6.44 for very high-risk disease.

Among the 46 studies reporting HRQoL outcomes (Table S3), 22 (48%) studies were conducted in Europe and North America, 9 (20%) studies were conducted in multiple countries or regions, and 2 studies were conducted in Turkey and Israel. Twenty-two studies (48%) were conducted among patients with MDS without risk stratifications, while 19 (41%) studies specifically focused on patients with low to intermediate risk of MDS, and 5 (11%) studies on higher risk of MDS. Twenty-four studies (52%) focused on HRQoL among patients with MDS, and 22 (48%) specifically assessed treatment-related HRQoL. The most frequently used cancer-specific HRQoL instruments were the European Organization for Research and Treatment of Cancer Quality of Life questionnaire-Core 30 (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy—Anemia (FACT-AN), together accounting for 55% of the included studies (Figure S3). Another commonly used generic HRQoL instrument was the EQ-5D-3L, which was used in 19% of included studies. The global score of the EORTC QLQ-C30 was reported in 13 studies. As shown in Figure S4a, the global score ranged from 50.6 to 66.7 at baseline. For patients with lower-risk MDS, the score ranged from 52.2 to 62.3, and for those with higher-risk MDS, the range was 50.6 to 59.7. There were 11 studies reporting EORTC QLQ-C30 dimension scores (Figure S4b). Physical functioning and role functioning were identified as the most affected domains, and cognitive functioning and social functioning were the least affected. Fatigue, pain, and appetite loss were the most severe symptoms, with nausea/vomiting being the least severe. The FACT-AN total score related to MDS was assessed in five unique studies (Figure S5). The FACT-AN total score ranged from 111 to 132, suggesting a moderate level of quality of life for patients with MDS. Health utility was measured in six studies, using the EQ-5D-3L in all six studies and EORTC Quality of Life Utility Core 10 Dimensions (QLU-C10D) in one study (Figure S6) [1-7]. The range of the health utility values was 0.73 to 0.83 measured by the EQ-5D-3L, and 0.73 to 0.77 measured by the EORTC QLU-C10D.

This study summarizes the evidence landscape on the epidemiological and humanistic burden of MDS. As the average age of populations in countries around the world continues to rise, the burden of MDS is expected to increase. Not only does MDS have a high mortality rate, it exerts a substantial impact on patients’ humanistic burden, which is affected by both disease- and treatment-specific considerations. However, the evidence base, particularly relating to epidemiology, is heterogeneous and disease-specific measures evaluating humanistic burden are lacking.

Determining the incidence and prevalence of MDS is crucial for understanding disease burden and optimizing healthcare resource allocation [8]. We found that ASIR ranges from 0.98 to 11.5 per 100,000, with higher rates among older adults and males. In a previous review that used the Surveillance, Epidemiology, and End Results data (SEER) data, Zeidan et al. similarly reported rising ASIR with age and a male predominance (4.7–7.7 per 100,000 in males vs. 2.5–3.4 per 100,000 in females) [9]. Zeidan et al. also reported that Asians have the lowest ASIR compared with other ethnicities, especially white [9]. However, data stratified by race and from non-Western countries remain scarce. This is an important gap as racialized groups remain underrepresented in drug trials in MDS [10]. Overall, our results align with a previous review, which reported the crude global prevalence of MDS as ranging from 0.22 to 13.2 per 100,000 across age groups, genders, and ethnicities [11]. Variation in study design and population characteristics makes comparison of these estimates across studies challenging [11]. MDS Survival remains poor, with 5-year survival ranging from 27% in Australia to 46% in Korea, varying by patient characteristics (e.g., age, sex) and disease risk (e.g., IPSS-R classification).

The EORTC QLQ-C30 and FACT-AN were the most commonly used instruments to measure HRQoL among patients with MDS [12, 13]. These well-established, validated, instruments for cancer patients are sometimes used alongside generic measures of HRQoL, such as the EQ-5D. Given the disease- and treatment-related effects on patients’ HRQoL, MDS-specific instruments may be better suited to capture the humanistic burden experienced by this patient population. Efforts are underway to develop such tools, including the MD Anderson Symptom Inventory (MDASI) for MDS/AML, the Quality of Life in Myelodysplasia Scale (QUALMS) and the 29-item psychometric Quality of Life E (QOL-E). Generally speaking, disease-specific instruments are more sensitive to different aspects of HRQoL and can provide more nuanced insight into the impacts of a disease and/or treatment on patients. Future studies should aim to validate these new disease-specific instruments among patients with MDS to facilitate their incorporation into randomized trials and economic evaluations of new and existing therapies.

The results of this review are subject to several limitations. First, the studies included were heterogeneous in terms of their study design, patient profile, and treatments received. As a result, data were summarized by subgroup when possible and without adjustment for differences. Note this is an inherent limitation of the current body of evidence and not of the review itself. Second, this review focused on patient burden only. It has been reported that, in certain cases, the burden of MDS is even more severe for caregivers than patients. Particularly with respect to mental health. Future research should seek to summarize caregiver burden for a more comprehensive understanding of the humanistic burden of disease.

The authors declare no conflicts of interest.