Global Incidence and Prevalence of Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) are relatively common hematological malignancies with varying reported incidence rates across different populations. Despite their significance, precise data on the global prevalence and incidence of MDS are still lacking.

Current epidemiological data indicates that the crude incidence of MDS ranges from 2.1 to 12.6 cases per 100,000 people per year according to multiple regional studies. However, these figures likely underestimate the real incidence as revealed by cohort studies that have identified previously unknown and asymptomatic cases.

The disease demonstrates a strong age-dependent pattern. Among the age group that is mainly affected (people older than 70 years), incidence rates increase substantially to about 15 to 50 cases per 100,000 people per year. A comprehensive 10-year study (1981-90) conducted in a population served by one district general hospital found a crude incidence rate of 12.6/100,000/year.

The age-specific incidence rates per 100,000 per year from this study revealed a dramatic increase with age: - 0.5 for age < 50 - 5.3 for age 50-59 - 15 for age 60-69 - 49 for age 70-79 - 89 for age 80+

This study concluded that MDS is more common than reported in previous studies and that incidence continues to rise into very old age.

Regional variations exist in the demographic patterns of MDS. A study from Pakistan (2010-2016) found a median age of 51 years at diagnosis with a male to female ratio of 3:1, which is younger than typically reported in Western populations. Similarly, studies from Vietnam and China have shown different patterns in chromosomal abnormalities compared to European populations.

Hypoplastic MDS (hMDS) appears to be a distinct clinicopathologic entity, accounting for about 15% of all MDS cases, while hypocellular MDS represents about 10-15% of MDS cases.

The challenges in establishing accurate global epidemiological data for MDS include difficulties in case ascertainment and differences in disease classification and diagnosis, which have made population-based studies an arduous endeavor. Currently, large-scale population-based studies required for obtaining truly representative data on the epidemiology of MDS are not available.

Our present knowledge of the incidence and other epidemiological characteristics of MDS is based on a few regional studies performed by authors with a long-lasting interest in these hemopathies. The recent increase in MDS incidence observed in some studies is probably not the result of an actual increase in the number of cases, but reflects improvements in geriatric medical care and diagnosis.

Study Design Parameters and Endpoints in Key MDS Trials

Study Design Parameters

Several observational population-based studies have been conducted to assess treatment patterns and outcomes in real-world MDS patients. These studies utilized registries such as HemoBase to collect patient data.

A 2022 study evaluated 55 patients between June 2000 and March 2015 with the aim of identifying prognostic factors and developing a model for survival prediction. This study employed Cox regression analysis on four key factors: age ≥55 years, Hematopoietic Cell Transplant-Comorbidity Index >2, intermediate or worse cytogenetic status based on the revised International Prognostic Scoring System, and unrelated donor status. A clinical risk model was constructed using the sum of regression coefficients and evaluated through receiver operating characteristic analysis and five-fold cross-validation.

Another important trial was a 2021 study that included 44 consecutive clinically suspected cases of MDS with refractory cytopenia(s) and 10 controls. This study divided patients into proven MDS cases (n=26) and suspected MDS (n=18). The study standardized flow cytometry (FCM) protocols across six French diagnostic laboratories between September 2013 and November 2015 and developed three maturation databases for different cell lineages.

Endpoints and Outcome Measures

The primary endpoints in multiple MDS studies were overall survival (OS) and event-free survival (EFS). In one key study, the median follow-up was 45.8 months (range: 1.27-193), with three-year OS and EFS rates of 61.8% and 56.4%, respectively. The areas under the curves (AUCs) for OS and EFS were 0.738 and 0.778, respectively.

Treatment duration was an important outcome measure, with different therapies showing varying durations: 5.8 months for hypomethylating agents, 1.7 months for intensive chemotherapy, 10.8 months for lenalidomide, and 14.8 months for erythropoiesis-stimulating agents.

Median OS after treatment discontinuation was another key endpoint, measured at 5.8 months after initial treatment, 9.3 months after second treatment, and 1.0 month after third treatment.

Diagnostic accuracy was assessed using flow cytometry scoring systems like the Ogata score and pattern analysis, with a flow score ≥3 correctly diagnosing 100% of proven MDS patients. Studies also evaluated the correlation between flow scores and the revised International Prognostic Scoring System (R-IPSS).

Some studies measured bone marrow microvessel density (MVD) and serum vascular endothelial growth factor (VEGF) to assess angiogenesis in MDS patients.

The treatment-associated risk (RR) for developing secondary myeloid neoplasms was evaluated using statistical methods such as Fine-Gray competing risk regression and Poisson regression.