News Release

A unique clinical trial leads to a dramatic decrease in early deaths from the rare and aggressive—yet highly curable—acute promyelocytic leukemia (APL)

In the first month of treatment, when APL patients were at the highest risk of death, a personalized care plan with 24/7 support from APL experts led to a 97% induction survival rate. Clinical trial EA9131 met its goal of preventing early deaths.

Reports and Proceedings

ECOG-ACRIN Cancer Research Group

Dr. Anand Jillella

image: Dr. Anand Jillella view more 

Credit: Augusta University

The use of a simplified treatment regimen by oncologists, along with management recommendations and 24/7 support provided by a limited and dedicated group of academic disease experts, resulted in a dramatic decrease in early deaths from acute promyelocytic leukemia (APL). The finding is from a multi-center prospective trial by the ECOG-ACRIN Cancer Research Group (study EA9131). The primary aim was to decrease induction (days 2-35) mortality from an estimated 30% to 15% or less. Study EA9131 met its primary objective, with a mortality rate of only 3.5%.

Lead researcher Anand P. Jillella, MD, presented the unique collaborative care model today at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans.

"A standardized algorithm with expert support decreases early deaths from APL and increases overall survival," said Dr. Jillella, a medical oncologist and APL expert at the Georgia Cancer Center and Medical College of Georgia at Augusta University. "Most oncologists currently lack access to simplified care instructions and institutional pathways for management recommendations to improve patient outcomes."

APL, a subtype of acute myeloid leukemia (AML), is extremely rare, with only about 3,000 new cases annually in the US. In addition, the treatment differs from the treatment of most other types of AML. As a result, many providers lack familiarity with how to treat this disease.

Prompt diagnosis and treatment of APL are critical because patients can quickly develop life-threatening blood clotting or bleeding problems if not treated emergently. With advances over the last decade, arsenic trioxide and non-chemotherapy drugs called differentiating agents, like all-trans-retinoic acid (ATRA), are now the standard APL treatments. These treatments are highly effective; however, the early death rate in APL is high at up to 30%.

"With our current therapies, APL, previously one of our deadliest leukemias, is now curable, and when that happens, people maintain their quality of life and go back to doing what they used to do. But these treatments cause side effects that are not typical of standard chemotherapy and can lead to death. Since most deaths from APL occur in the first 30 days of treatment, if patients survive the first month, it's a home run," said Dr. Jillella.

The three most common causes of early death during the induction period are bleeding, infection, and differentiation syndrome, the latter caused by complications that develop from the treatment. Other risk factors for mortality include older age (over 60 years), comorbid conditions, especially obesity, and the complexity of APL at presentation.

"In my opinion, many early deaths from APL are preventable, and I don't think there is any good reason for most of these patients to die," said Dr. Jillella. "Involvement of clinicians familiar with the potential complications is critical."

The EA9131 collaborative care model provided contact with a disease expert who suggested ways to adjust or personalize standard treatment based on the patient's disease status and risk factors. A total of 202 patients enrolled in the trial; 62 at six lead academic centers and 140 at 37 community hospitals through the National Cancer Institute (NCI) Community Oncology Research Program (NCORP).

There were no exclusions for eligibility based on patient age or general health status.

"Clinical trials for APL tend to enroll younger patients with no comorbid conditions, whereas the general population of APL patients tends to be elderly and with comorbidities," said Dr. Jillella. "However, since many patients present to hospitals where the doctors are not familiar with the intricacies of managing APL, they can benefit from the guidance of someone with more experience."

Seven deaths (3.5%) occurred during the induction period, all due to differentiation syndrome, with four at lead centers and three at community sites. Six of seven deaths were among the elderly (69-91 years).

One-year survival was 94.5%, with no difference between academic and community centers.

"Dr. Jillella has demonstrated that by providing guidance, we can truly optimize the care of and prevent early deaths in APL patients," said ECOG-ACRIN Leukemia Committee Chair Selina M. Luger, MD, the study's APL expert at the University of Pennsylvania's Abramson Cancer Center in Philadelphia.

"This model provides us with a framework to enhance the care of patients with other complex diseases who cannot participate in clinical trials or travel to academic medical centers even if they have limited resources or significant medical comorbidities."  

The trial was funded by the Division of Cancer Prevention at the National Cancer Institute, part of the National Institutes of Health.

"Based on these results, we are evaluating other ways to provide guided assistance for patients with complicated leukemias and treatment," said Dr. Luger. "Additionally, results of this study have provided insight into treatment modifications for APL patients with significant comorbidities that allow them to achieve remission without additional toxicities."

Abstract 421 – A Simplified Patient Care Strategy to Decrease Early Deaths in Acute Promyelocytic Leukemia (APL): Results of the ECOG-ACRIN EA9131 Trial, part of Session 613. Identifier: NCT03253848.

About the Collaborative Care Plan

After a successful pilot test at NCORP community sites in Georgia and South Carolina, with Dr. Jillella and a colleague serving as the APL experts, he brought the program to the ECOG-ACRIN Leukemia Committee, where he is a member. Together, they developed EA9131 as a prospective trial.

There were seven academic APL experts at six lead academic centers. They include the Mayo Clinic in Minnesota, Mayo Clinic in Jacksonville, Florida, Medical College of Georgia, Memorial Sloan Kettering Cancer Center, Northwestern University, and the University of Pennsylvania's Abramson Cancer Center.

At the lead centers, the treating oncologists managed their patients with input from the local expert. At the community centers, oncologists contacted one of the seven experts as soon as a patient presented with suspected APL by email or phone. Expert support was available 24/7, and the patient was eligible for enrollment if there was contact with the APL experts within 72 hours of initiating therapy.

The experts provided a suggested initial work-up and treatment plan to the treating physician, then maintained communication throughout induction. Therapy recommendations followed the standard of care, but dose reductions were suggested for older age and comorbidities. For patients with more complex medical issues, all seven experts often discussed the case and made a consensus recommendation.


The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN comprises nearly 1300 member institutions in the United States and around the world. Approximately 15,000 physicians, translational scientists, and associated research professionals from the member institutions are involved in Group research. For more information, visit, follow us on Twitter @eaonc, Facebook, and LinkedIn, or call 215.789.3631.


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