MIAMI — Acute promyelocytic leukemia (APL) APL was first reported and described in Norway in 1957, and is connected to the proliferation of promyelocytes, catastrophic hemorrhagic incidences, and hyper-acute onset.

A new review in Oncotarget discusses advances in treatment of APL, which accounts for 10%–15% of all acute myeloid leukemias.1

Authors from the University of Miami’s Miller School of Medicine and the Miami VAMC noted that the cancer is characterized by a block in differentiation where leukemic cells are halted at the promyelocyte stage. In 94% of cases, they add, a characteristic balanced chromosomal translocation between chromosomes 15 and 17 t (15;17) (q24; q21) is present, with the translocation resulting in the formation of the PML-RARA fusion protein.

“Initially remarkable” cure rates followed the introduction of retinoic acid (RA) and arsenic trioxide (ATO), according to the report, but authors added, “Relapsed APL, particularly in the high-risk subset of patients, remains an important clinical problem.”

Another issue, they added, is that, “Despite the success of ATRA & ATO, many clinicians still elect to use cytotoxic chemotherapy in the treatment of APL. Patients who become resistant to ATO have an increased risk of mortality.”

APL patients are  risk-stratified into three groups- low, intermediate, and high according to white blood cell counts. Low and intermediate subset of patients — defined by a WBC of less than 10,000/µL – are often grouped together.

“Although intermediate as well as low-risk patients may be treated without the use of cytotoxic chemotherapy, the combination of ATRA and ATO alone is not sufficient to treat high-risk patients,” according to the authors. “The treatment of high-risk patients, (defined as having a WBC count greater than 10,000/µL)- involves administration of cytotoxic chemotherapy.

They noted that an evaluation of four clinical trials involving low risk APL patients (WBC count ≤ 10 × 109/L) from 2010–2014 showed overall survival rates ranging from a low of 86% after three years to a high of 99% after four years. In addition, according to the authors,  evaluation of three clinical trials from 2015–2017 involving high risk APL patients (WBC count > 10 × 109/L) showed overall survival rates ranging from a high of 88% after three years to a low of 86% after five years.

“The probability of relapse is significantly higher in the high-risk subset of patients undergoing treatment for APL; however, approximately 10–20% of APL patients relapse regardless of their risk stratification,” the review explained.

The authors pointed out that 20-25% of patients undergoing treatment will develop differentiation syndrome, a common side effect of differentiation agents. Recent evidence using in vitro models has shown that mutations in the B2 domain of the PML protein, mediate arsenic resistance.

“Alternative agents and approaches considering these clinical outcomes are needed to address ATO resistance as well as the relapse rate in high risk APL,” according to the review.

  1. Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget. 2020;11(11):992‐ Published 2020 Mar 17. doi:10.18632/oncotarget.27513