Acute Myeloid Leukemia (AML) is characterized by rapid-onset uncontrolled proliferation of hematopoietic progenitor cells due to defects in their maturation program. The malignant cells compete with healthy cells for space in the bone marrow, resulting in reduced numbers of platelets and red & white blood cells (pancytopenia).
Complications of pancytopenia (e.g., severe hemorrhages and infections) are a frequent cause of death in these patients. Although the basis of AML treatment (chemotherapy) has not changed for decades, substantial progress has been made with supportive care (i.e., blood transfusions, platelet transfusions, antibiotics, antifungals) and allogeneic stem cell transplantation. As a result, cure rates of 40%-50% can now be achieved in fit patients. However, the outcome of older patients is still very poor, in particular for patients that are not fit for intensive chemotherapy. AML is a relatively rare disease. Commonly affecting elderly individuals, the incidence of AML is expected to increase as a result of the aging of our population and the rising number of cancer survivors (i.e., secondary AML).
AML survival rates are very poor, in particular in unfit patients, so the main urgent unmet medical need of AML patients is better treatments (i.e., novel drugs, novel drug combinations, and more personalized treatment choices). A large number of new drugs are awaiting clinical application. Careful selection of patient groups that are likely to benefit from these new drugs by detailed molecular profiling is high on the research agenda. By pooling data from multiple clinical trials, HARMONY researchers will create a dataset of ~4000-5000 AML patients. We aim to identify molecular profiles that can predict clinical course and drug response, facilitating personalized patient management. Examples of key questions that HARMONY may address using this dataset include:
How do combinations of genetic mutations relate to disease course and treatment response?
How can we improve the measurement of minimal residual disease?