Early mortality in acute promyelocytic leukemia: Potential predictors (Review)

Abstract

Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10–15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure. In the present study, published data was reviewed with a focus on the factors associated with early mortality. When treated with ATO as a primary treatment, the fms-like tyrosine kinase-internal tandem deletion has no impact on early mortality. Low lymphoid enhancer binding factor-1 expression may be a reliable marker for early mortality and the target of therapy if it could be proven by further studies. Cluster of differentiation (CD)56+ and CD34+/CD2+ may be candidates to select high-risk patients. The risk of early mortality in APL still cannot be predicted via the cell surface makers, despite multiple studies on their prognostic significance. Typically, a complex translocation did not alter the survival rate in patients with APL; however, if an abnormal karyotype [e.g., Ide(17), ZBTB16/RARα and STAT5B/RARα] appeared singularly or as part of a complex mutation, there is a high possibility of early mortality if clinicians are unable to identify or monitor it.

Impact of insurance status on the survival of younger patients diagnosed with acute promyelocytic leukemia in the United States

“…16,17 However, with recent advancements in treatment and supportive care, there has been documented improvement in early mortality rates in patients with APL within the United States over the past few decades. [10][11][12][13] Furthermore, for CAYAs, insurance status did not influence outcomes for those surviving 2 months after diagnosis. Therefore, in addition to early mortality, access to care in terms of the need for immediate diagnosis, urgent initiation of treatment in cases of APL, and the need for prolonged hospitalization, including intensive care unit/tertiary-level care, to manage severe complications of APL 15 may act as a potential barrier for uninsured patients.…”

“…8,9 Furthermore, with improved supportive care, the 5-year mortality rates for patients with APL have declined significantly from nearly 80% to approximately 40%. 10 Despite these encouraging results, mortality from complications of APL remains high. Early mortality due to hemorrhagic complications is often reported: up to 10% in clinical trials and even higher in the general population.…”

“…Early mortality due to hemorrhagic complications is often reported: up to 10% in clinical trials and even higher in the general population. 10,11 Diagnostic delays, delays in the administration of ATRA, and suboptimal supportive care are all factors influencing the outcomes of patients with APL. [11][12][13] Whether the improved results observed in clinical trials with ATRA and ATO translate to the general population remains unclear.…”

Whole exome sequencing detects CHST3 mutation in patient with acute promyelocytic leukemia

“…The combined use of ATRA and ATO as primary therapy has markedly improved the survival rate of patients with APL. [ 3 ] However, mortality in the first 30 days following therapy remains a major contribution to treatment failure. It was reported that immunophenotyping and complex karyotype maybe help us to identify high-risk patients of early death.…”

“…It was reported that immunophenotyping and complex karyotype maybe help us to identify high-risk patients of early death. [ 3 ] CD56 + and CD34 + /CD2 + may be candidates to select high-risk patients. While in this patient, leukemia cells were negative for CD56 or CD34.…”