Lower Dose of Arsenic Trioxide in Induction Therapy for Acute Promyelocytic Leukemia Achieves Same Long-Term Survival Outcome: A Real-World Retrospective Study

Introduction: The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) makes acute promyelocytic leukemia (APL) a highly curable leukemia. According to the 2024 National Comprehensive Cancer Network (NCCN) guidelines, the first-line treatment for APL is arsenic trioxide 0.15 mg/kg IV daily plus ATRA 45 mg/m ² until the blood count recovery by day 28. For high-risk patients, this regimen is combined with age-adjusted idarubicin or gemtuzumab ozogamicin. However, the hematological and nonhematological toxic effects of ATO including leukocytosis, corrected QT (QTc) interval prolongation and liver injury usually lead to inevitable interrupting ATO treatment before day 28. We noticed that patients in our center who received an insufficient dosage of ATO in induction treatment achieved same long-term survival outcomes as patients who received standard-dose. In this study, we aim to present the real-world treatment outcomes and long-term survival of ATO patients who received low-dose ATO treatment.

Method: This study includes newly diagnosed de novo APL patients who completed the induction treatment at our center from January 2013 to December 2023, regardless of whether they achieved complete remission. All patients were diagnosed in accordance with the French‑American‑British (FAB) criteria. Patients with other previous myeloid neoplasms or died before undergoing ATO treatment were excluded. Clinical data, including risk classification results, treatment regimen, the dosage of ATO treatment in induction therapy and survival status were included. We categorized patients into a standard-dose group and a low-dose group, depending on whether the dose of ATO use was up to 28 days or not. The relationships between ATO dosage groups and other patient characteristics were investigated using Fisher’s exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables. Survival analyses were conducted using the Kaplan-Meier method.

Results: 156 patients were diagnosed with APL in our center and completed induction treatment with ATO 10mg intravenously daily. 45 patients received ATO for 28 days, while 111 patients did not receive full-course of ATO treatment due to hematologic or non-hematologic toxic effects. The median age of patients at diagnosis is 43 years in the standard-dose group and 45 in the low-dose group, and there is no difference between two groups (p=0.272), as well as the sex ratio of two groups (p=0.527). According to WBC count, 35 patients in low-dose group and 84 patients in standard-dose group are classified as low risk, 10 patients in low-dose group and 27 patients in standard-dose group are classified as high risk, and there is no statistical difference between two groups (p=0.780). In induction therapy, the incidence of raised liver ALT or AST is 75.5% in standard-dose group and 73.8% in low-dose group (p=0.827)，while the incidence of QTc Interval prolongation is 31.1% in standard-dose group and 49.5% in low-dose group (p=0.036). Of the 156 patients, 41 (91.1%) in standard-dose group and 106 (95.5%) in low-risk group achieved complete remission at the end of the first induction therapy, with no statistical difference between two groups (p=0.287). After a median follow-up of 5.6 years, 22 patients are lost to follow-up; the remaining 34 patients in the standard-dose group and 100 patients in the low-dose group all received long-term survival.

Conclusion: Our single-center retrospective study shows that patients who received ATO treatment lower than the NCCN standard dose achieved the same complete remission rate and long-term survival status. Patients receiving ATO treatment have a high rate of adverse events in both groups, reducing the total ATO dosage at induction treatment may reduce the adverse event rate and help patients achieve the same long-term survival.