Using advanced genetics technologies to monitor for remaining cancer cells after treatment may soon become an effective tool to inform treatment decisions and ultimately predict outcomes for patients with a particularly aggressive form of acute lymphocytic leukemia (ALL).
Approximately 25% to 30% of all adults with ALL, the second most common type of acute leukemia, have Philadelphia chromosome-positive (Ph+) ALL, a rapidly progressing form of the disease caused by a genetic abnormality that has a poor prognosis. An allogeneic stem cell transplant is a common preventive treatment following first remission, but it has harsh side effects and is not universally available.
Tyrosine kinase inhibitors (TKIs) have greatly improved survival rates and may make stem cell transplantation unnecessary for some Ph+ ALL patients. However, clinicians lack a reliable method to predict disease progression and to determine whether a patient’s disease is aggressive enough to warrant a stem cell transplant or if TKI therapy plus chemotherapy will likely eradicate the disease. Monitoring the cancer cells that remain in the patient’s body after the primary course of treatment, which is the minimal residual disease (MRD), may effectively indicate a patient’s risk for relapse.
To better understand how technology that tracks indicators of MRD could potentially predict Ph+ ALL patients’ survival and inform treatment decisions, Farhad Ravandi, MD, of The University of Texas MD Anderson Cancer Center in Houston and a team of researchers conducted a decade-long study to monitor whether a negative MRD reading was associated with prolonged survival. The study results were published in Blood (2013; doi:10.1182/blood-2009-03-213389).
Between 2001 and 2011, Dr. Ravandi’s team monitored 76 adult patients (average age 54 years) with Ph+ ALL who had achieved complete remission after a treatment regimen including at least one course of induction chemotherapy plus a TKI followed by treatment with a TKI (either dasatinib or imatinib) and chemotherapy, and two years of TKI maintenance therapy. All study participants began with fewer than 5% cancer cells in their body and none had undergone stem cell transplant, nor were they at an otherwise heightened risk of relapse. Investigators monitored patients for MRD after first remission and every three months thereafter.
Combining multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RQ-PCR) was effective in predicting the majority of disease progression and patient outcomes in this population. Among 44 patients who showed evidence of MRD in the first year of follow-up (either by MFC or RQ-PCR results), 13 relapsed, including 9 of 22 of the highest risk patients who showed positive MFC at three months and beyond. Thirteen of 54 patients who maintained negative MRD from three months and beyond relapsed.
While the MRD readings observed by Dr. Ravandi and his team did not accurately predict all patient outcomes in the study population, researchers note that these results indicate that the combination of MFC and RQ-PCR technologies represents a valuable prognostic tool to measure the likelihood of a patient relapse.