Clinical Trials, Advanced Genetic Profiling, Improved Patient Categorization Have Led to Improved Outcomes in Acute Myeloid Leukemia since 1996
NCCN has published the 20th annual edition of the NCCN Guidelines® for Acute Myeloid Leukemia, one of the original NCCN Guidelines published in 1996.
FORT WASHINGTON, PA — Acute Myeloid Leukemia is the most common form of acute leukemia among adults with more than 18,000 estimated diagnoses in 2014, and accounts for the largest number of annual deaths from leukemias in the United States.
The National Comprehensive Cancer Network ® ( NCCN ® ) has published the 20th annual edition of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia (AML) —one of the original NCCN Guidelines® published in November 1996.
“Looking back on the very simple principles upon which the panel constructed the acute leukemia guidelines, it is interesting to see that, while much has changed, the principles still remain the same,” said Margaret R. O’Donnell, MD, FRCPC, Clinical Professor and Associate Clinical director, Hematology and Hematopoietic Cell Transplantation, City of Hope , and Chair, NCCN Guidelines Panel for AML. “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.”
Dr. O’Donnell, who has chaired the NCCN Guidelines Panel for AML since 1996, noted, since the inception of the AML panel, that clinical trials were to be considered as a high priority in initial therapy. One of the highlights in AML therapy has been the identification of the PML/RARA fusion gene in acute promyelocytic leukemia, which led to clinical trials from all corners of the world (United States, China, and Europe) incorporating all trans retinoid acid (ATRA) and arsenic trioxide (ATO) first in combination with chemotherapy and now as a standalone regimen. Results in pre-clinical studies have been promising, yielding 95 to 98 percent complete remission and survival of more than 90 percent at two years, according to a study published in the New England Journal of Medicine . 
In the intervening years, added Dr. O’Donnell, the Genome Project led to discovery of biologic prognosticators from the macro level of karyotypic gains and losses to molecular mutations at the base pair level; gene expression profiling and epigenetic modulation remain research tools for the present.
Patient categorization has led to further success in treatment, Dr. 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 consideration 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 comorbid conditions that restrict treatment options,” said Dr. O’Donnell. “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.”
“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, MD, 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.”
Today, NCCN develops and maintains 60 NCCN Guidelines, covering 97% of malignant cancers affecting people in the United States. The NCCN Guidelines are developed and updated through an evidence-based process in which the expert panels integrate comprehensive clinical and scientific data with the judgment of the multidisciplinary panel members and other experts drawn from NCCN Member Institutions . Access to the complete library of NCCN Guidelines is available free-of-charge at NCCN.org .
In January, NCCN celebrated its 20th anniversary and on March 12 – 14, 2015, NCCN will host its 20th Annual Conference: Advancing the Standard of Cancer Care ™ at The Diplomat in Hollywood, Florida. In recognition of its 20th anniversary, NCCN will host a special live roundtable during the conference featuring NCCN leadership—past and present—as well as other stakeholders who have had a significant impact on the development, progressions, and success of NCCN over the years. Noteworthy historical NCCN accomplishment and events will be discussed, as well as the impact NCCN has had and continues to have on the quality, effectiveness, and efficiency of cancer care so that patients can live better lives.
To learn more about NCCN, the NCCN Guidelines, and the NCCN 20th Annual Conference, visit NCCN.org .
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 25 of the world’s leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers.
The NCCN Member Institutions are: Fred and Pamela Buffett Cancer Center, Omaha, NE; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT.
 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Myeloid Leukemia (Version 1.2015). © 2015 National Comprehensive Cancer Network, Inc. Available at: NCCN.org. Accessed February 26, 2015. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org.
 Ref Lo-Coco f, Avvisati G, Vignetti M etal. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia NEJM 2013 369:111-121
Katie Kiley Brown, NCCN