Pre-Empting Relapse

Acute myeloid leukemia (AML) is the most common type of blood cancer in adults. Starting suddenly and progressing rapidly, even those who achieve remission can’t breathe easy; as many as one-third of patients who receive chemotherapy and a bone marrow transplant will relapse within three to six months. Unfortunately, transplantation is the only curative treatment for AML, so patients who relapse are left with few options.

Zhaolei Zhang, Principal Investigator in the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research, believes a new DNA-based technique will improve the long-term survival of AML patients by predicting relapse after treatment. Using next generation sequencing (NGS), the test can detect mutations in the bone marrow that indicate the presence of treatment-resistant cancer cells. Although chemotherapy eliminates most of these leukemia cells, some persist after the patient has received a bone marrow transplant. The test can detect these mutations in the bone marrow three weeks after transplant, indicating that the cancer will likely return. “The early detection of actionable mutations after transplantation will increase the number of targeted therapeutic interventions available before relapse occurs, improving survival chances,” Zhang says.

“After 21 days post-transplantation, we observed that close to 60 percent of patients with these treatment-resistant mutations relapsed, whereas only around 15 percent of those without the mutations relapsed,” continues Zhang. Until now, the high cost of NGS assays made the analysis of such large amounts of generated data a challenge. However, technological advances and the development of sophisticated computational methods have made NGS assay analysis feasible. Zhang’s team hope to replicate the observations of their study in multiple hospital sites and with larger cohorts before eventually getting regulatory approval for the test’s use in clinics.