Children with acute myeloid leukemia benefit from improved diagnostic test
Long-term outcomes for children with acute myeloid leukemia (AML) are predicted by early treatment responses. Flow cytometry has been identified as better for checking for minimal residual disease than two other widely used methods to predict patient survival, according to research led by St. Jude Children's Research Hospital.
Flow cytometry can identify a single cancer cell in 1,000 normal cells that remain in patient bone marrow after the initial intensive weeks of chemotherapy. Cancer cells are distinguished from normal cells in flow cytometry based on different cell surface markers and other molecules. Flow cytometry is commonly used to guide the treatment of acute lymphoblastic leukemia (ALL), which is the most common childhood cancer. Notably, AML targets different white blood cells than ALL does. Fewer children and adolescents are affected by AML, about 500 per year in the United States, and AML has a lower long-term survival rate than ALL (71% vs 94%).
Responses to AML treatment are evaluated on day 22 of therapy and at the end of each treatment phase. The responses are a powerful predictor of patient survival, and they guide ongoing therapy and identify patients who are candidates for more intense treatment. This study compared the power of three accepted approaches to predict AML treatment outcome in young AML patients whose disease was diagnosed between 2002 and 2008. Among the 203 patients with AML who were enrolled, 1,514 bone marrow samples were examined by flow cytometry, 1,382 by microscopy, and 508 by polymerase chain reaction (PCR).
The minimal residual disease measured by flow cytometry was an independent predictor of patient outcome, since a worse prognosis and greater risk of relapse or treatment failure was associated with having even one leukemia cell in 1,000 normal cells in bone marrow after the first or second round of therapy. In contrast, microscopy had limited value for gauging treatment response. Though the microscope has been used for decades to evaluate patient responses to therapy, the problems identified include an inability to distinguish those cells destined to become leukemia cells from normal cells and misclassification of about 10% of patients as being in remission when flow cytometry identified leukemia cells in the same bone marrow.
Further, the utility of flow cytometry meant that PCR was unnecessary for most AML patients. Generally, PCR overestimated the presence of leukemia cells, as it identified 197 of 311 samples as having leukemia cells. However, flow cytometry showed that only 19 actually harbored minimal residual disease.
For a subgroup of AML patients who had mixed lineage leukemia gene changes, PCR testing was valuable in predicting outcome and guiding therapy.“These results will help establish flow cytometry testing for minimal residual disease as a routine tool for guiding therapy of acute myeloid leukemia and identifying patients early who are at risk of treatment failure,” stated Hiroto Inaba, MD, PhD, an associate member of the Department of Oncology at St. Jude, and the first and corresponding author of the study.