Gurnari C, et al. APL 2017:PO041

ATO and ATRA for the treatment of childhood APL


Acute promyelocytic leukemia (APL) accounts for about 5%–10% of all cases of childhood acute myeloid leukemia, with the disease being significantly more frequent in children of Mediterranean origin.1 Recent studies with adult patients with standard-risk APL have shown that combined therapy with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) leads to impressive cure rates and has a milder toxicity profile than standard chemotherapy regimens.2 However, data on the use of ATO and ATRA in childhood APL are scarce. At the 7th International Symposium on APL, Gurnari and colleagues presented results from a collection of cases of pediatric patients with APL given the ATO and ATRA regimen.3

Study design

  • From April 2014 onwards, 17 children with APL were treated in seven Italian centres.
  • They were given the ATO and ATRA combination regimen, as reported by the Gruppo Italiano Malattie Ematologiche dell’Adulto, the German-Austrian Acute Myeloid Leukemia Study Group, and Study Alliance Leukemia.

Key findings

Baseline characteristics

  • The median age at diagnosis was 13 years (range: 4–17).
  • Sixteen of the 17 children belonged to the standard-risk group (white blood cell [WBC] count ≤10,000/μL), while the remaining child had high-risk APL (WBC count >10,000/μL).


  • All patients achieved hematological complete remission (CR) after induction therapy.
  • All 14 patients who completed treatment achieved molecular CR.
  • Neither hematological nor molecular relapses occurred during a median follow-up of 13 months (range: 2–41).
  • Median hospital stay was 30 days (range: 15–43) during the induction phase.
  • Consolidation courses were administered on an outpatient basis.
  • Patient characteristics are presented in Table 1.


  • Coagulopathy was present at diagnosis in 12 of 17 patients, and resolved during induction with no major complications.
  • Hyperleukocytosis during therapy occurred in 10 of 16 standard-risk patients, with a median peak on Day 7.
  • There were no cases of differentiation syndrome.
  • Liver toxicity (a temporary increase in alanine aminotransferase/aspartate aminotransferase levels) occurred in nine patients:
    • Grade 1 in four patients;
    • Grade 2 in four patients; and
    • Grade 3 in one patient.
  • Two patients experienced transient corrected QT (QTc) interval prolongation (0.5 seconds).
  • Pseudotumor cerebri was observed in one patient during consolidation.
  • Hematological toxicities of varying severity were observed in all patients. (Table 1)
  • Temporary treatment discontinuation was necessary in seven patients because of:
    • Grade 3 liver toxicity;
    • Prolonged QTc interval;
    • Fever; and
    • Pseudotumor cerebri.

Table 1. Patient characteristics and treatment-related side effects

Key conclusions

  • The results presented indicate that the ATO and ATRA combination is safe and highly effective in childhood APL.
  • The observed acute treatment-related side effects were transient and manageable.
  • Although only one child with high-risk APL was treated, the favourable outcome suggests that this subset of patients may also benefit from this combination treatment.

References: 1. Kutny MA, Gregory J, Feusner JH. Treatment of paediatric APL: How does the therapeutic approach differ from adults? Best Pract Res Clin Haematol 2014;27(1):69–78. 2. Platzbecker U, Avvisati G, Cicconi L, et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non–high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol 2017;35(6):605–12. 3. Gurnari C, Strocchio L, Vinti L, et al. Arsenic trioxide and all-trans retinoic acid for treatment of childhood acute promyelocytic leukemia. Intl. Symposium on APL Abstracts 2017:CO041.