Improved Diagnostic Test Benefits Children with Leukemia

The laboratory technique of flow cytometry makes it possible to identify a single cancer cell in a thousand normal cells that remain in patient bone marrow after the initial intensive weeks of chemotherapy.

The method showed that checking for minimal residual disease (MRD) by flow cytometry was better than two other widely used methods for predicting patient survival from acute myeloid leukemia (AML) and the results help identify who might benefit from more intensive therapy, including bone marrow transplantation.

Investigators at St. Jude Children’s Research Hospital (Memphis, TN, USA) studied 203 AML patients enrolled in a clinical trial whose disease was diagnosed between 2002 and 2008. The project marked the first time MRD was used to guide therapy. During the study, scientists examined 1,514 patient bone marrow samples by flow cytometry. Of those samples, 1,382 also had information regarding microscopic evaluation and 508 of polymerase chain reaction (PCR) amplification of fusion transcripts.

The flow cytometry analysis showed that minimal residual disease measured by flow cytometry was an independent predictor of patient outcome. The finding of even one leukemia cell in 1,000 normal cells in bone marrow after the first or second round of therapy was associated with a worse prognosis and a greater risk of relapse or treatment failure.
The scientists concluded microscopic examination had limited value for gauging treatment response. Problems ranged from an inability to distinguish between cells destined to become leukemia cells and normal blood cells to classifying about 10% of patients as being in remission when flow cytometry identified leukemia cells in the same bone marrow.

Investigators also concluded that flow cytometry rendered PCR testing unnecessary for most AML patients. The analysis found PCR testing generally overestimated the presence of leukemia cells. In this study, PCR identified 197 of 311 patient samples as containing leukemia cells. Flow cytometry of the same samples showed just 19 actually harbored detectible minimal residual disease. They did find PCR testing valuable in predicting outcome and guiding therapy for a subgroup of AML patients with mixed lineage leukemia (MLL) gene changes.

Hiroto Inaba, MD, PhD, the lead author said, “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.” The study was published on October 10, 2012, in the Journal of Clinical Oncology.

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St. Jude Children’s Research Hospital