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Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time

Periodic Reporting for period 4 - MDS-RIGHT (Providing the right care to the right patient with MyeloDysplastic Syndrome at the right time)

Reporting period: 2019-11-01 to 2020-10-31

Healthy ageing is one of the major challenges for the European community, as ageing usually introduces health problems and increased healthcare (HC) utilization. Both myelodysplastic syndromes (MDS) and anemia limit quality of life (QoL) and increase the pressure on HC. MDS is a chronic bone marrow malignancy usually occurring in persons of 70 years or older. Shortages in blood cells, leading to anemia, infections and/or bleeding complications, are typical characteristics of MDS. The majority (75%) of patients with MDS are classified as lower-risk (LR), which is associated with an 8-years loss of life expectancy compared to healthy older population. A considerable number of LR-MDS-patients (estimated 2 million European citizens) remains ‘under diagnosed’ as anemia of the elderly (AoE), due to insufficient awareness of the relevance of a right diagnosis and the reluctance to use bone marrow puncture in elderly. Consequently, these persons do not receive proper care. The MDS-RIGHT project aim has been to address the complex challenges associated with correct diagnosis and treatment of patients with MDS or AoE, using data from the European MDS Registry (EUMDS) and a community-based Dutch population (Lifelines). The main goal was to compare long-term outcomes and costs, as well as approaches to diagnose and to treat elderly with MDS and chronic anemia of unknown cause; to assess (epi)genetic abnormalities; and to develop more effective and safer evidence-based, tailored healthcare interventions (HCI) for these persons, resulting in better treatment compliance and more cost-effective and safer use of HCI.
MDS care is challenging and complex, as MDS is a heterogeneous disorder and most available HCI do not cure MDS, but generally aim to improve the bone marrow function and to restore the numbers of blood cells. The EUMDS registry is ideally suited for comparing the effectiveness of available HCI for this predominantly elderly patient group. The Registry holds longitudinal observational data from more than 2,698 MDS patients with up to 12.5 years follow-up in 16 EU countries and Israel. Comparisons of this ‘real life’ data helped to identify the most (cost-)effective treatment strategies. MDS-RIGHT objectives were:
1 Comparing outcome and costs of existing HCI using data from the comprehensive EUMDS Registry
2 Enhancing compliance with diagnostic procedures in MDS, by introducing new diagnostic methods
3 Maximizing QoL by restricting MDS-specific HCI to patients with the right diagnosis, who are likely to benefit from these HCI
4 Providing models that can better predict the likely response of a patient to a certain treatment (‘treatment-outcome prediction models’), to support personalized decision making and robust economic analyses
5 Developing improved, evidence-based diagnostic and therapeutic guidelines, based on the outcomes of objectives 1-4
6 Establishing a European MDS competence network encompassing all stakeholders for dissemination and utilization of up-to-date, evidence-based and regulatory guidance.
We showed that:
1 treatment with ESA is more effective when initiated before progression to transfusion dependent anemia
2 effective iron chelation clearly improved overall survival (OS)
3 regular red blood cell transfusions were associated with impaired progression-free survival
4 the negative impact of chronic transfusions was already detectable at very low transfusion density (< 1 unit/month, not considered as regular transfusion dependency in the current guidelines)
5 transfusion dependency was associated with a more rapid decline of QoL
6 excess iron exclusively occurred in regularly transfused patients and patients with ring sideroblastic MDS and was associated with an impaired OS.
A rapid decline of platelets during the first 6 months after diagnosis was associated with impaired OS. This may decrease the need for invasive bone marrow aspirates to monitor prognosis and deterioration in patients with LR-MDS. The prevalence of clonal hematopoiesis was higher (47%) in the anemic persons from the general population (Lifelines) compared to the non-anemic persons (39%). Characterization of individual cases by new genetic markers showed that mutation profiling identified meaningful clusters of LR-MDS with distinct molecular pathways, clinical features, response to HCI and endpoints. This will improve classification and individual risk assessment of MDS patients and provides evidence for research and development of targeted HCI.
Both MDS and anemia in individuals >60 years (Lifelines) were found to reduce QoL. New predictors for low QoL have been identified, which will contribute to more personalized care and maximizing patients’ QoL. We established a European MDS multi-stakeholder Competence Network, the MDS-Europe website, and the new publicly available online dynamic evidence-based MDS guideline ( The MDS-RIGHT consortium developed Manifesto, a call to improve the care for patients with MDS, is published on
The MDS-RIGHT project has nearly completed all tasks. Results have been shared in at least 30 peer-reviewed publications. We developed interactive evidence-based treatment guidelines for diagnosis, prognosis and person-oriented interventions for MDS, based on up-to-date patient and disease-specific characteristics and a well-functioning website for communication. This website will be maintained and expanded beyond the MDS-RIGHT project, supported by additional funding from pharmaceutical companies and collaboration with the HTx consortium, and a recently developed MDS-Hub.
Almost all potential impacts as defined in our project have been achieved. New data of MDS-RIGHT and recent published literature have been incorporated in the interactive guidelines. The new data will continue to promote more effective diagnostic and prognostic procedures by identifying more specific patient groups who will benefit more likely from available HCI and from more personalized care. This will contribute to more cost-effective use of resources and to healthier ageing and increased wellbeing of this anemic, often chronically transfused, population. MDS-RIGHT will also improve awareness of HRQoL and vigilance of AoE.
We established a formal collaboration with the HTx-project. This will allow us to increase the output on health economics in specific interventions, including treatment with ESA and iron chelators beyond the official program of MDS-RIGHT.
The role of the identified MDS-specific mutations in the general population, is becoming more and more relevant as exemplified by a dedicated editorial in the high-ranking journal Blood in the same issue as the publication by van Zeventer et al. This data inspired us to extend our consortium to several other general population and disease-specific cohorts. Funding is being sought, to address, amongst others, the role of these MDS-specific mutations in other chronic complex conditions (CCC). These mutations are playing an important role in the inflammatory and immune regulatory processes in these CCC.
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