Week-12 MRD negativity and HSCT improve survival in pediatric KMT2A-rearranged lymphoid neoplasms
The study reports a single-center retrospective analysis of 47 children with KMT2A-rearranged precursor lymphoid neoplasms, evaluating clinical outcomes and prognostic markers. Patients achieving minimal residual disease negativity by week 12 of induction therapy via quantitative PCR and those receiving hematopoietic stem cell transplantation during first remission demonstrated significantly higher 3-year overall survival and event-free survival rates compared to their respective non-transplant or MRD-positive cohorts. Multivariate analysis confirmed both factors as independent protective predictors for event-free survival. These findings underscore the diagnostic utility of early qPCR-based MRD monitoring to guide transplant decisions in this aggressive pediatric malignancy.
The original study
[Clinical characteristics and prognosis of pediatric precursor lymphoid neoplasms with KMT2A gene rearrangement].
- Authors
- Zhu YY, Ma P, He YY, Zhou JW, Huang S, Wang YF, et al.
- Journal
- Zhonghua er ke za zhi = Chinese journal of pediatrics
- Type
- English Abstract, Journal Article
- PMID
- 42527137
Original abstract
Objective: To investigate the clinical characteristics and prognostic factors of pediatric precursor lymphoid neoplasms with KMT2A gene rearrangement. Methods: In this retrospective cohort study, clinical data of 47 children with KMT2A gene rearrangement precursor lymphoid neoplasms diagnosed at the Children's Hospital Affiliated to Zhengzhou University from January 2018 to November 2024 were collected, so as to describe their clinical characteristics. According to whether hematopoietic stem cell transplantation (HSCT) was performed during first complete remission (CR1), children were divided into CR1 transplantation group and CR1 chemotherapy group, survival rates comparison and prognostic factor analysis were performed between two groups. For relapsed children in the CR1 chemotherapy group, they were further subdivided into a transplantation salvage group and a chemotherapy salvage group based on salvage therapy modality, and post-relapse survival rates were compared between the two subgroups. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were analyzed using the Cox proportional hazards regression model. Results: Among the 47 patients, there were 27 males and 20 females, with the age of 0.8 (0.4, 2.4) years. B-cell acute lymphoblastic leukemia accounted for 85% (40 cases). The initial white blood cell count was 89×10⁹ (27×10⁹, 302×10⁹)/L. Central nervous system leukemia was diagnosed in 10 children(22%, 46 children had central nervous system assessment). A total of 43 children were included in the efficacy evaluation, with a follow-up of 30.1 (13.8, 47.7) months. The 3-year overall survival and event-free survival (EFS) rates were (68.2±7.3) % and (51.7±8.0) %, respectively. The CR1 transplantation group (17 children) had significantly better 3-year overall survival and EFS rates than the CR1 chemotherapy group (26 children)(100.0% vs. (47.2±10.1) %, (84.7±10.3) % vs. (29.6±9.1) %, χ²=12.68 and 16.03, both P<0.001). The transplantation salvage group (4 children) had a higher 18-month overall survival rate than the chemotherapy salvage group (14 children) (100.0% vs. (8.9±8.4)%, χ²=10.07, P=0.002). Multivariate analysis showed that negativity of minimal residual disease detected by quantitative real-time PCR (qPCR-MRD) at week 12 of induction therapy (HR=0.29, 95%CI 0.10-0.83, P=0.022) and HSCT (HR=0.15, 95%CI 0.05-0.44, P<0.001) were both independent protective factors for EFS. Conclusion: Pediatric KMT2A gene rearrangement precursor lymphoid neoplasms are clinically highly aggressive and have a poor prognosis, but negative qPCR-MRD at week 12 of induction therapy and HSCT are independent protective factors for EFS.