Intensive chemotherapy with dual induction and ALL-like consolidation for childhood acute myeloid leukemia: a respective report from multiple centers in China

Abstract

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed.

Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation.

Design: Retrospective, single-arm study.

Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023.

Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 10⁹/L, 11 of whom ⩾100 × 10⁹/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 10⁹/L (n = 59) and ⩾100 × 10⁹/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%).

Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 10⁹/L was the only independent risk factor in this cohort.

Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.

Keywords: Acute lymphoblastic leukemia elements; Event-free survival; Overall survival; Pediatric acute myeloid leukemia.

Figure 1.

ZSYY-AML-2012 protocol. BM is usually performed on the 15th day of induction and after the first, fourth, and fifth consolidation. On the 15th day of induction, we only check the examination of marrow smear while we also check for FCM, positive fusion gene, or mutation after consolidation. IT, intrathecal injection of cytarabine and dexamethasone, is done on the 15th and 21st day of chemotherapy. AML, acute myeloid leukemia; Ara-C, cytarabine; BM, bone marrow; DNR, daunorubicin; FCM, flow cytometry; MA, mitoxantrone; 6MP, 6-mercaptopurine; MTX, methotrexate; PEG-asp, pegaspargase; VCR, vincristine; VP16, etoposide.

Figure 2.

Flowchart of patients enrolled in the 2012 AML protocol. All 70 patients shown above were included in the analysis. *Transplantation due to the demand of his parents. AML, acute myeloid leukemia.

Figure 3.

(a) Kaplan-Meier curve of 5-year event-free survival among 70 pediatric patients; (b) Kaplan-Meier curve of 5-year overall survival among 70 pediatric patients; (c) The percentages of all patients with relapse; (d) Kaplan-Meier curve of 5-year event-free survival among 70 between WBC ⩾ 100 × 10⁹/L group and WBC < 100 × 10⁹/L group; (e) Kaplan-Meier curve of 5-year event-free survival among 70 between M2 group and M5 group; (f) Kaplan-Meier curve of 5-year event-free survival among 70 between poor prognostic marker and no poor prognostic marker group.