Background: Patients with higher-risk myelodysplastic syndromes (HR-MDS), if left untreated have lower overall survival (OS), progress to acute myeloid leukemia (AML) and increased burden. This systematic literature review (SLR) identified comprehensive evidence on clinical burden among patients with MDS.

Methodology: Literature search of English publications from 2011-2021 was conducted in Embase^®, MEDLINE^® and MEDLINE^®-In-process to identify relevant studies fulfilling pre-defined inclusion criteria. Data on study characteristics, patient demographics and clinical burden were extracted.

Results: 67 studies fulfilled eligibility criteria. Patients with HR-MDS were four-times less likely to survive compared to low-risk MDS (LR-MDS) over 85 months (HR:4.46, CI:2.8-7.1, p<0.001). Presence of comorbidities, abnormal karyotype and transfusion dependency were predictive of low survival with HR-MDS. Progression to AML was time-dependent and significantly associated with decreased survival (HR:1.80, CI:1.27-2.55, p<0·001). There was a high propensity of progression to AML among HR-MDS patients versus LR-MDS patients and time for AML transformation was shorter. AML transformation rate increased by 1.5-fold among HR-MDS patients, from first to second year of MDS diagnosis. Cardiovascular disorders and diabetes were common comorbidities, while anemia, thrombocytopenia and neutropenia lead to major symptom burden. Impact of IPSS-R categories on EuroQoL-5D scoring, was only marginal and varied per age, gender, comorbidities and transfusion requirement. Among HR-MDS patients, blood transfusion led to reduction in anemia and fatigue symptoms (p=0.016). Low quality of life (QoL) was associated with reduced survival. Increased age, male gender, increased comorbidities and increased blood transfusion significantly impacted QoL.

Conclusion: There is substantial clinical burden associated with MDS; age, gender, cytogenetics, comorbidities and blood transfusion being the predominant factors that predict survival and QoL. A transformation from MDS to AML was observed in large number of patients. Thus, there is a clear need for newer therapies focusing on improving symptoms and OS, particularly amongst HR-MDS patients.