Acute myeloid leukemia research in the era of advanced genetic sequencing: an exercise in knowledge translation

The identified need is the reduction of occurrence of relapse of AML following allogeneic HCT, as the prognosis of this patient group is very poor.

Capstone Summary:

Allogeneic hematopoietic cell transplantation (HCT) may offer survival benefit to patients with acute myeloid leukemia (AML) (Koreth et al, 2009, Cornelissen et al, 2007). A major challenge when treating AML patients with allogeneic HCT is disease relapse, with a one-year post-relapse survival less than 20% (Devillier et al, 2013). An even bigger challenge is predicting relapse, as AML is a genetically complex disease and there are currently no widely established sensitive tools. The gold standard for determining treatment response in AML is by microscopic examination of bone marrow and assessment of irregular, immature “blast” cells, with less than 5% blasts considered to demonstrate remission. Leukemia-associated immunophenotypes (LAIPs), which are defined at diagnosis by multi-parameter flow cytometry (MFC), can be used for monitoring in patients with AML (Kern et al, 2010). Studies using MFC on marrow samples pre-allogeneic HCT show that any level of detectable minimal residual disease (MRD) is associated with an increased risk of relapse (Walter et al, 2013). However the routine use of MFC may be complicated by issues such as the possible shift in antigen expression post-allogeneic HCT as well as the issue of standardization of the method in that particular setting.

Capstone Team: 

Prof. Fotios (Frank) Michelis, MD PhD MHScTR MD PhD MHScTR

Staff Hematologist, Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre Assistant Professor, Department of Medicine, University of Toronto Staff Hematologist, Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre Assistant Professor, Department of Medicine, University of Toronto

 

Capstone Supervisor:

Prof. Joseph Ferenbok, PhD

Translational Research Program Temerty Faculty of Medicine University of Toronto
Revolutionary Translator Director

Capstone Advisory Committee:

Prof. Uri Tabori, MD

Haematology/Oncology, The Hospital for Sick Children The Arthur and Sonia Labatt Brain Tumour Research Centre Paediatrics and Institute of Medical Sciences, University of Toronto
Staff Oncologist Scientist Assistant Professor Genetics & Genome Biology Principal Investigator

Aaron D Schimmer, MD, PhD, FRCPC

Princess Margaret Cancer Centre
Senior Scientist

Hans Messner,


"The TRP really speaks to the patient-centred approach to research.”

 - Connie Putterman, Parent Advocate, Cohort 2017