Study Subjects and Methods
1. Study subjects
A total of 28 children with NF1 mutation-positive acute leukemia who were treated at Beijing Children’s Hospital, Capital Medical University, between January 2017 and February 2024, including 12 patients with acute lymphoblastic leukemia (ALL), 15 with acute myeloid leukemia (AML), and one with acute promyelocytic leukemia (APL), were enrolled in this study. Patient information, including sex, age, immunophenotype, gene mutations, fusion genes, bone marrow, minimal residual disease (MRD), extramedullary involvement, NF1 mutation sites and modes, and signs of neurofibromatosis, was collected. ALL patients were treated with the Chinese Children Leukemia Group (CCLG)-ALL 2018 regimen, AML patients were treated with the CCLG-AML 2015 or 2019 regimen depending on the time of the first visit, and APL patients were treated with the CCLG-APL 2016 regimen. The diagnosis of neurofibromatosis type I was made according to the standard revision of the International Consensus Group on Diagnostic Criteria of Neurofibromatosis 20212. This study was approved by the Medical Ethics Committee of Beijing Children’s Hospital(IEC-C-006-A04-V.07.1).
2. Gene detection methods
Bone marrow samples were collected at the first visit and sent to Beijing Haester Medical Laboratory for analysis of the mutational landscape of ALL and 248 AML-related mutations using oral mucosal epithelial DNA as a somatic tissue control.
3. Follow-up
The treatment and survival outcomes of the patients were followed up through telephone interviews and outpatient services. The follow-up period ended on June 30, 2024, and the median follow-up period was 16 (1.2–85.5) months. Overall survival (OS) was calculated starting from the time of leukemia diagnosis until the last follow-up visit or death.
4. Statistical analysis
SPSS 26.0 statistical software was used for data processing. Measurement data with a non-normal distribution are expressed as M (Q1, Q3), and enumeration data are expressed as percentages (%). Survival analysis was conducted using Kaplan‒Meier curves, and the log-rank test was performed. P <0.05 was considered to indicate a statistically significant difference between two groups. A retrospective case‒control design was used to compare the survival outcomes of children with NF1 mutation-positive AML with those of children with NF1 mutation-negative AML admitted during the same period; the patients were matched by the random number method of 1:3, and matching factors included age±2 years, sex, risk stratification, treatment protocols, and transplantation status.