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

Overview:

The identified need is the reduction in the 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.

Despite the difficulties in organizing the multidisciplinary collaboration that was necessary to get the research project off the ground, it was interesting to note that the collaboration in bio-banking and molecular research between the multiple services of the research center was something that was previously desired by most participating parties for a prolonged period of time- years even- yet without result until the current initiative was taken.

Capstone Team: 

Frank Michelis

 

Capstone Advisory Committee:

Dr. Hans Messner
Dr. Aaron Schimmer
Dr. Uri Tabori

 

TRP Faculty Lead:

Dr. Lucy Osborne