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.

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.

Students:

Prof. Fotios (Frank) Michelis

MD, PhD, MHScTR

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

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

MD, PhD, FRCPC
Princess Margaret Cancer Centre
Senior Scientist

Hans

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

Prof. Fotios (Frank) Michelis

MD, PhD, MHScTR

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

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.

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 Supervisor:

Prof. Joseph Ferenbok

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

Capstone Advisory Committee:

Prof. Uri

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

MD, PhD, FRCPC
Princess Margaret Cancer Centre
Senior Scientist

Hans