In a study reported in JCO Oncology Practice, Anand P. Jillella, MD, and colleagues found that physician education on the main causes of death during induction treatment for acute promyelocytic leukemia (APL)—and comanagement of cases with expert physicians—resulted in a low early mortality rate and high 1-year survival in a cohort of patients with APL treated at community centers.

As stated by the investigators, “Recent population-based studies have shown that outcomes in acute myeloid leukemia were worse when managed in community centers compared with academic centers.”

Anand P. Jillella, MD

Study Details

The study involved development of a simplified algorithm using standardized treatment guidelines focusing on prevention and early treatment of the main causes of death during induction (bleeding, differentiation syndrome, and infection). Oncologists at 32 treatment centers in four U.S. states, including 29 community centers and 3 academic centers, were educated about early deaths over a 6-month period. The patient population consisted of 118 evaluable patients enrolled at these sites between September 2013 and April 2016 who received induction with all-trans retinoic acid (ATRA) alone or in combination with arsenic trioxide (AIO) or chemotherapy. Overall, 73 patients (62%) were treated in community centers and 45 (38%) in academic centers.

Four large leukemia centers were identified as lead sites, with experts from these sites being responsible for engaging in communication with participating leukemia treatment centers. An expert was contacted when APL was suspected, with the algorithm being made available followed by discussion of treatment plans. Communication between expert and treating physician was frequent in the first 2 weeks (the time period when most early deaths occur). At the end of induction therapy, recommendations were given to the treating physicians on the best choice of consolidation therapy. Early death was defined as death from the time of diagnosis until the end of induction, or death after 30 days as a result of complications from induction.

Key Findings

Among 118 evaluable patients, 10 (including 6 non–high-risk and 4 high-risk patients) had early death, yielding an early mortality rate of 8.5%. Early death occurred in four patients treated at academic centers (9.1%) and six treated at community centers (8.1%). The cause of death was differentiation syndrome in five patients, coagulopathy in three, differentiation syndrome and infection in one, and infection in one.

Among 108 patients achieving remission during induction, relapse occurred in 7 (6.4%).

The 1-year overall survival probability for the entire cohort was 87.3%. After 18 months from the first visit of the last patient enrolled and median follow-up of 27.3 months, the overall survival rate was 84.5%. No difference in overall survival was observed between patients treated at academic center vs those treated at community centers.

The investigators observed, “In this study, we show that it is possible to improve 1-year survival in patients treated in community clinics when comanaged by an APL expert and the local treating physician. The outcomes in 29 community centers were similar to the three academic centers both at the end of induction…and at 1 year. Overall, the 1-year survival rate in this study of 87.3% is superior to the U.S. Surveillance, Epidemiology, and End Results data that showed a relative survival rate of 70.7%. The overall long-term survival of 84.5% with a median follow-up of 27.3 months is higher than what is seen in published population-based studies.”

They concluded, “Induction mortality can be decreased and population-wide survival improved in APL with the use of standardized treatment guidelines. Support from experts who have more experience with induction therapy is crucial and helps to improve the outcomes.”

Dr. Jillella, of Georgia Cancer Center at Augusta University, is the corresponding author for the JCO Oncology Practice article.

Disclosure: The study was supported by a grant from the Leukemia and Lymphoma Society. For full disclosures of the study authors, visit ascopubs.org.