Гипометилирующая терапия до трансплантации эффективна при миелодиспластических синдромах у детей, но не работает при ювенильном миеломонцитарном лейкозе

Pretransplant hypomethylating therapy demonstrated disease-specific efficacy in pediatric myeloid malignancies, with decitabine producing deeper remissions and improved survival in myelodysplastic syndromes (MDS), while juvenile myelomonocytic leukemia (JMML) derived less measurable response despite maintaining favorable posttransplant outcomes. This pooled analysis, published in Clinical Epigenetics, included 87 pediatric patients from 7 studies, comprising 51 with MDS and 36 with JMML treated with azacitidine or decitabine prior to allogeneic hematopoietic stem cell transplantation. Median age across the cohort was 5 years, and patients received a median of 3 treatment cycles. At last follow-up, 76.9% of evaluable patients were alive, with mortality primarily attributed to relapse and transplant-related complications. In the MDS cohort, complete remission was achieved in 64.7% of patients and was strongly associated with decitabine exposure (P <.0001). This translated into a marked survival advantage following transplantation, with 84.2% of patients in complete remission alive at a median follow-up of 4.4 years compared with 42.8% among those with progressive disease (P <.001). Stable disease (17.6%) and partial remission (3.9%) were less frequent. Treatment response was not significantly influenced by age, blast percentage, cytogenetics, or most mutational profiles. Read more about MDS therapies In contrast, the JMML cohort exhibited limited responsiveness to hypomethylating agents (HMAs). Partial remission (47.2%) and progressive disease (41.7%) predominated, while complete remission was observed in only 11.1%. Treatment response was not associated with the use of azacitidine or decitabine, genetic alterations, or most clinical variables. Older age correlated with progressive disease (P <.05), suggesting a potential age-related resistance pattern. Comparative analyses confirmed significantly higher complete remission and stable disease rates in MDS relative to JMML (64.7% vs 11.1% and 17.6% vs 0%, respectively; P <.0001 and P <.001). Conversely, JMML demonstrated higher rates of partial remission and progressive disease (47.2% vs 3.9% and 41.7% vs 13.7%; P <.000001 and P <.001). PTPN11 mutations were significantly associated with multiple clinical parameters, including treatment response (P <.0001), highlighting their biological relevance. These findings suggest that the differential efficacy of HMAs reflects underlying disease biology, with epigenetic dysregulation predominating in MDS and RAS/MAPK pathway activation driving JMML. Although pretransplant epigenetic therapy may enhance remission depth in select populations, its role relative to upfront transplantation or conventional chemotherapy remains to be defined in prospective pediatric studies. “These findings underscore that while HMAs can effectively reduce disease burden and potentially improve transplant outcomes in MDS, their utility in JMML may be constrained by underlying disease biology, highlighting the need for tailored pre-transplant strategies and combination approaches to better optimize efficacy,” stated the authors. This article originally appeared on Rare Disease Advisor. References: Cianflone A, Cecere F, Coppola L, Cacace F, Mirabelli P, Tambaro FP. Azacitidine and decitabine show distinct response patterns in pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia before HSCT: a systematic review and quantitative analysis. Clin Epigenetics. Published online July 1, 2026. doi:10.1186/s13148-026-02191-0