Project Leaders:
Aly Karsan, Marco Marra

Lead Institution:    
BC Cancer Agency

Technology Applications:    
Personalized medicine

Research Funding Program:    
Genomics & Health: Personalized Medicine Program

Acute myeloid leukemia (AML) affects approximately 200 British Columbians per year, and is fatal without appropriate therapy. Treatment options include chemotherapy and allogeneic stem cell transplantion (SCT). While stem cell transplantation can be a successful treatment for some patients, it is associated with high risk of medical complications, high cost to the health care system, and not all patients will benefit. Indeed some patients will die from the acute toxicity of the transplantation procedure. Certain genetic markers can be used to predict whether a patient would be a good candidate for SCT, or whether conventional chemotherapy is a more appropriate option. Currently chromosomal analysis plus two molecular genetic markers are tested by the clinical Cancer Genetics Laboratory at the BC Cancer Agency to allow physicians of the Leukemia/Bone Marrow Transplantation Program of British Columbia to choose between the therapeutic options.

However, as worldwide research uncovers more predictive markers, there is a need to expand the genetic analysis in order for our clinicians to make more informed treatment decisions for our patients. There are at least two other genes that harbor mutations in AML that assist in choosing therapy that have already become standard of care according to international guidelines that are not currently being evaluated. Recent advances in technology at the BC Cancer Agency’s Genome Sciences Centre have made genomic sequence analysis a possible option for diagnostic assessment. In this study, we propose to assess a strategy to use genomic analysis of the diseased cells to identify all the specific markers in AML patients that will allow clinicians to choose the best treatment option for each individual patient. Our team of clinicians and sequencing experts will determine the most suitable genomic analysis technology to use, and will compare the technology to current diagnostic procedures. This assessment will include a health economics evaluation to determine the most cost-effective approach to providing the best testing for our patients. Our end goal is to replace existing methods with a single genomic analysis assessment, which can test for a wide-range of markers keeping testing costs at a sustainable level as future research uncovers other clinically relevant markers.

While this large scale analysis of patient genetic material would be valuable in terms of reducing costs in the health care system, it would also provide clinicians with more information than the leukemia-related mutations present in AML cells. There are social benefits from this much expanded genome information, but there could also be risks in terms of misuse. Hence this project will assess potential risks for individuals and groups and the current state of genetic information management and privacy protection and identify current attitudes and practices of handling genetic information among lab physicians and clinicians.

Not only will this project and subsequent implementation serve to contain future testing costs, but this study will also provide proof-of-concept for other cancers, where it is becoming clear that multiple gene mutations need to be tested in order to select the best therapy. Thus the ability to test for multiple mutations in different cancers will be imperative with the new therapies being developed, and we hope and expect that successful completion of this project will allow us to make the costs of the required genetic testing sustainable.