Acute myeloid leukemia: Revised treatment guidelines reflect progress
April 1, 2015 | by Nicole White
Acute myeloid leukemia is the most common form of acute leukemia among adults, accounting for 18,000 diagnoses in 2014.
Two decades ago, in 1996, the National Comprehensive Cancer Network (NCCN) published its first guidelines for treatment of acute myeloid leukemia, or AML. Margaret O'Donnell, M.D., associate clinical director of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, has chaired the guidelines panel since then. Those guidelines have undergone multiple revisions since that time, reflecting changing practice and increasing knowledge. They were recently revised yet again.
"Looking back on the very simple principles upon which the panel constructed the acute myeloid leukemia guidelines, it is interesting to see that, while much has changed, the principles still remain the same," O'Donnell said. "We believed that it was our mandate to incorporate the best of current knowledge in the areas of prognostic indications, treatment and supportive care, but with a strong bias that we should not settle for the mediocre outcomes that were the norm at that time."
While this form of leukemia remains the leading cause of leukemia deaths in the United States, key advances in treatment and diagnosis have made the disease more treatable and curable. One of the highlights has been the identification of a specific leukemia gene. The identification of that gene led to clinical trials in the U.S., China and Europe focused on new combination therapies. Using all-trans retinoid acid, or ATRA, and arsenic trioxide has proven to be especially potent: Preclinical studies yield up to 98 percent complete remission and survival of more than 90 percent at two years, according to a 2013 study in the New England Journal of Medicine.
At the same time, the Genome Project has led to the discovery of genetic markers that continue to be studied, along with gene expression and the epigenetics of the disease.
Patient categorization has led to further success in treatment, O’Donnell said. In patients for whom remission is not achieved, refinement of risk groups has helped clinicians better identify those for whom hematopoietic stem cell transplantation represents the best strategy.
“With the graying of America, another significant change in the guidelines is a focus on the older population, who is most at risk for developing this disease and who often have co-morbid conditions that restrict treatment options,” O’Donnell said. “Today, much more thought is placed on designing clinical trials for older patients ‘unfit for chemotherapy’ or who have disease characteristics such as complex cytogenetics or antecedent myelodysplasia for whom the outcomes with standard chemotherapy are poor.”
The NCCN guidelines are important tools for doctors treating the disease, and the organization's guidelines cover 97 percent of malignant cancers in the U.S.
“Acute leukemia is an incredibly aggressive disease for which clinicians and patients are faced with a multitude of decisions in a short amount of time,” said Robert W. Carlson, M.D., chief executive officer, NCCN. “NCCN is proud to have provided AML treatment teams with evidence-based, transparent treatment recommendations for two decades to allow for appropriate choice in patient management.”
City of Hope continues to seek out better treatments and cures for AML and other blood cancers. O'Donnell's work on the guidelines reflects that determination.
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