Abstract
Objective: To summarize the clinical characteristics, treatment effects and survival outcomes of children with NF1 mutation-positive acute leukemia. Methods : The clinical data and prognosis of 28 patients with NF1 mutation-positive acute leukemia treated at Beijing Children’s Hospital, Capital Medical University, between January 2017 and February 2024 were retrospectively analyzed. Results : A total of 28 patients were included in the study, with a median follow-up of 16 (1.2–85.5) months. Twelve patients had acute lymphoblastic leukemia, of whom 75.0% were at intermediate risk. Complete response (CR) was achieved in the bone marrow after induction chemotherapy, with a minimal residual disease (MRD) of 1×10-3 at Day 33. Fifteen patients had acute myeloid leukemia (AML), of whom 66.7% were at high risk. The CR rate in the bone marrow was 86.6% at Day 28. Eleven (73.3%) patients survived at the end of follow-up. One patient with acute promyelocytic leukemia had standard risk and a good response. The overall survival rate of children with NF1 mutations was comparable to that of children with no mutations. However, children with germline NF1 mutations had a poor prognosis compared with those with somatic mutations, especially in AML patients. The frequency of NF1 mutations was 2–87.7%. The clinical manifestations of 3 patients with neurofibromatosis included café-au-lait macules, freckles, xanthogranuloma, scoliosis, and benign intracranial lesions. Conclusion: Most NF1 mutations in children with acute leukemia are somatic mutations that do not affect overall survival. Children with leukemia complicated with neurofibromatosis should undergo lifelong follow-up.
Leukemia is the most common cancer and major cause of death in childhood, and chromosomal abnormalities or genetic events such as gene mutations and fusion genes occur over the course of the disease.NF1 is a tumor suppressor gene and a negative regulator of the RAS pathway. Mutations in this gene may lead to neurofibromatosis type 1 (OMIM 613113). In addition, the risk of benign and malignant tumors is increased. Among pediatric hematological diseases, NF1 mutations are frequently observed in juvenile myelomonocytic leukemia (JMML)1. Moreover, these mutations are associated with the pathogenesis of JMML and its poor clinical prognosis. However, there are few reports on this gene in pediatric acute leukemia. Data on the clinical characteristics, treatment effects and prognosis of patients with NF1 mutation-positive acute leukemia are lacking. In this study, the clinical and molecular biological characteristics, treatment effects and survival status of 28 children with NF1 mutation-positive acute leukemia were retrospectively collected and analyzed to provide a reference for clinical diagnosis and treatment.