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Arsenic Plus All-Trans Retinoic Acid for Pediatric Patients With Acute Promyelocytic Leukemia


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In a Chinese study (CCLG-APL2016) reported in the Journal of Clinical Oncology, Zheng et al found that the combination of arsenic with all-trans retinoic acid (ATRA) was associated with good survival outcomes in pediatric patients with acute promyelocytic leukemia.

Study Details

The multicenter trial enrolled 186 evaluable patients between November 2016 and November 2018. Patients were divided into a standard-risk cohort (n = 107) and a high-risk cohort (n = 79); standard risk was defined as baseline white blood cell count of < 10 × 109/L without FLT3-ITD mutation, and high risk was defined as either baseline white blood cell count of ≥ 10 × 109/L or FLT3-ITD mutation. Standard-risk patients received a 28-day induction regimen and 14-day consolidation with ATRA plus either intravenous arsenic trioxide or oral arsenic, with high-risk patients also receiving a reduced-dose anthracycline in induction and consolidation. Patients in complete molecular remission received maintenance with four (standard-risk group) or five cycles of ATRA plus arsenic. The primary endpoints were event-free survival and overall survival at 2 years.

Key Findings

Median follow-up was 28.9 months.

KEY POINTS

  • Event-free survival at 2 years was 97% in the standard-risk group and 90% in the high-risk group.
  • Overall survival at 2 years was 99% in the standard-risk group and 95% in the high-risk group.
  • Arsenic levels in plasma, urine, hair, and nails declined to within normal ranges by 6 months after the end of treatment.

Event-free survival at 2 years was 97% (95% confidence interval [CI] = 93%–100%) in the standard-risk group and 90% (95% CI = 83%–96%) in the high-risk group (P = .252). Overall survival at 2 years was 99% (95% CI = 97%–100%) in the standard-risk group and 95% (95% CI = 90%–100%) in the high-risk group (P = .088). The cumulative incidence of relapse at 2 years was 2% vs 6% (P = .921).

Plasma arsenic levels were significantly elevated after treatment, reaching a stable effective level of 42.9 to 63.2 ng/mL during treatment. Arsenic levels in plasma, urine, hair, and nails declined to within normal ranges by 6 months after the end of treatment.

During induction, disseminated intravascular coagulation occurred in 52% of patients, including grade 2 in 16%, grade 3 in 29%, and grade 4 in 6%. Death due to severe disseminated intravascular coagulation with intracranial hemorrhage occurred in three patients (2%). Differentiation syndrome occurred in 41% of patients, with no associated deaths. Grade 3 or 4 neutropenia occurred in 80% of patients and grade 3 or 4 thrombocytopenia in 89%. Grade 3 transaminitis occurred in five patients (3%) and grade 1 or 2 hyperbilirubinemia in 8%. Decreased left ventricular ejection fraction was observed in one patient (< 1%), with no patients having prolonged corrected QT interval.

No common signs of chronic arsenic poisoning—including cardiovascular events, chronic renal insufficiency, diabetes, and neurologic dysfunction—were observed during follow-up.

The investigators concluded, “Arsenic combined with ATRA is effective and safe in pediatric patients with acute promyelocytic leukemia, although long-term follow-up is still needed.”

Tianyou Wang, MD, of Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Science and Technology Key Projects, Beijing Municipal Administration of Hospitals DengFeng Program, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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