Impact of Qualified Dedicated APL Leukemia Specialist and Simplified Treatment Algorithm on Early Deaths in APL, a Monocenter Experience

Introduction: Acute Promyelocytic Leukemia (APL) is a highly curable subtype of Acute Myelogenous Leukemia (AML). Since the incorporation of all-trans-retinoic acid ATRA and arsenic trioxide (ATO) survival rates for APL are reported to be >90% in clinical trials. Despite this, there is a discrepancy in survival rates in general practice, mainly due to significant early deaths (ED). Some national registries report 20-30% of patients die during induction.

Major factors contributing to ED are due to rarity of the disease, advanced age, underlying comorbidities, lack of written guidelines for induction, delay in diagnosis, and physician experience level. Herein, we report our observations on the incorporation of a simple treatment algorithm and management by leukemia/APL experts on ED.

Methods: Retrospective monocenter analysis of ED in APL patients who underwent induction therapy from 4/2007 to 3/2022. All APL patients who underwent induction therapy were stratified into 2 treatment groups. Patients in group 1 treated from 4/2007-12/2009 and 1/2014- 6/2017 by a hematologist without an algorithm. Group 2 patients were treated from 1/2010-12/2013 and 7/2017-03/2022 by an APL leukemia specialist using a written algorithm. Induction rate mortality was compared between both groups. The algorithm was a two-page set of guidelines directed at preventing or treating the major causes of early death. Institutional review board approval was obtained for this review.

Results: Between 4/2007 and 3/2022, n=62 patients were analyzed. A total of n=5 patients were excluded from the study; n=3 passed away or were transitioned to hospice care prior to starting any form of induction therapy and n=2 were Jehovah's Witnesses who refused all blood products. A total of n=57 patients were stratified into their respective groups. Across all groups (n=10, 17.5%) reported ED, median age 68 (range 20-81), (n=6, 60%) patients >60 years of age.

Group 1 consisted of n=23 patients, median age 53 (range 20-78), (n=12, 52.2%) were male, and (n=9, 39.1%) were high risk (WBC > 10,000/mm³). Incidence of ED was (n=9, 39.1%) from disseminated intravascular coagulation DIC (n=3), differentiation syndrome DS (n=4), multi-organ failure (n=1), infection (n=1). ATRA was initiated at suspicion of APL diagnosis in (n=23, 100%) of patients. ATRA given alone in (n=1, 4.3%) patients, combined with ATO in (n=8, 34.8%), with chemotherapy in (n=19, 82.6%), and (n=5, 21.7%) with ATO/ATRA/chemotherapy.

Group 2 consisted of n=34 patients, median age 51 (range 10-88), (n=14, 41.2%) were male, (n=10, 41.2%) were reported as high risk. There were (n=1, 2.9%) reported ED from DIC. ATRA was initiated at suspicion of APL diagnosis in (n=34, 100%) of patients. ATRA was given alone in (n=7, 20.6%) patients, combined with ATO in (n=17, 50%) and chemotherapy in (n=8, 23.5%). ATRA/ATO/chemotherapy was administered in (n=6, 17.6%).

Conclusions: Results of this retrospective study showed that a simplified treatment algorithm and management by APL experts decreased early death rates from 39.1% to 2.9%. This data is promising and has important implications for both academic centers and community practices.

Kolhe:Bioanano INc: Honoraria, Research Funding, Speakers Bureau; Perkin Elmer: Honoraria, Research Funding; Agena: Honoraria, Research Funding; Qiagen: Honoraria, Research Funding; Cepheid: Honoraria; PGDx: Honoraria, Research Funding; Illumina: Research Funding. Kota:Pfizer Inc: Honoraria, Research Funding; Xcenda: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Ariad: Honoraria.