Myelodysplastic Syndromes (MDS) are characterized by morphological abnormalities in one or more of the major myeloid cell lineages of hematopoiesis. They are caused by somatic mutations in hematopoietic stem cells. Patients with MDS suffer from cytopenia (i.e., a reduction in the number of mature blood cells) and they have a propensity to develop acute myeloid leukemia (AML).
MDS shows marked clinical heterogeneity, ~70% of patients suffering from “low risk” MDS with a low risk of AML progression but cytopenias (mainly anemia), and ~30% suffering from “high risk” MDS, with high risk of AML progression and short survival. Fit high-risk patients may potentially be cured with allogeneic hematopoietic stem cell transplantation, but this treatment can be applied in about 15 % of MDS patients. Other high-risk patients are usually treated with hypomethylating agents, which prolong survival rather than cure the patient. Life expectancy is always reduced in high-risk patients (median survival of 2 years). Usually affecting elderly individuals, the incidence of MDS is expected to increase as a result of the aging of our population and the rising number of cancer survivors (i.e., secondary MDS).
By pooling data from multiple clinical trials and databases, the first work of in MDS HARMONY will be the creation of a dataset of ~4000 high risk MDS patients. A substantial subgroup of these (~1700) have been particularly well-studied, including for instance data on somatic mutations. Examples of key questions that HARMONY will address using this dataset include:
How do molecular data relate to disease course and treatment response?
Which rare side-effects can we observe in patients that are treated with hypomethylating agents?
Can we identify new outcomes to effectively evaluate the efficacy of new treatments after a shorter observation period?