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Background <p>Epigenetic dysregulation is a key therapeutic target in pediatric hematologic malignancies resistant to conventional chemotherapy, where allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. In this setting, hypomethylating agents (HMAs), such as azacitidine (AZA) and decitabine (DAC), are increasingly used as pre-transplant bridging strategies to reduce disease burden and enhance treatment sensitivity. Their integration with HSCT may improve pre-transplant remission rates, prolong complete remission, and increase the likelihood of durable disease control and cure. However, evidence in pediatric patients remains limited. Here, we performed a systematic review and pooled analysis to evaluate the efficacy of pre-HSCT epigenetic therapy in pediatric hematologic malignancies.</p> Results <p>A pooled analysis of seven studies of 87 pediatric patients including 51 Myelodysplastic Syndromes (MDS) and 36 Juvenile Myelomonocytic Leukemia (JMML) treated with DAC or AZA prior to HSCT was performed. Statistical analyses used chi-squared or Fisher’s exact tests for categorical variables and non-parametric tests for continuous variables, with correction for multiple comparisons. In MDS, Complete remission (CR) was achieved in 64.7% of patients and strongly associated with DAC, translating into improved post-HSCT survival compared to PD (84.2% vs. 42.8%). In JMML, partial remission (PR) and progressive disease (PD) predominated (47.2% and 41.7%, respectively), while CR was rare (11.1%); response was not associated with HMA type or genetic features, although older age correlated with PD. Comparative analysis confirmed superior responses in MDS (higher CR and SD) versus JMML, which showed higher PR and PD rates. PTPN11 mutations were significantly associated with multiple clinical variables, including treatment response.</p> Conclusions <p>Pre-transplant HMA therapy shows variable efficacy in pediatric myeloid malignancies. DAC induces rapid, deep responses in MDS, improving post-HSCT survival. JMML responds less, yet post-transplant survival remains favorable. Higher HMA responsiveness in MDS likely reflects predominant epigenetic dysregulation, whereas JMML is mainly driven by aberrant RAS/MAPK pathway activation. These results emphasize that pre-transplant strategies should be tailored to the specific biological and clinical context of each disease. However, their impact relative to upfront HSCT or conventional chemotherapy remains to be definitively determined.</p> Graphical abstract <p></p>

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Azacitidine and decitabine show distinct response patterns in pediatric Myelodysplastic Syndromes and Juvenile Myelomonocytic Leukemia before HSCT: a systematic review and quantitative analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Alessandra Cianflone,
  • Francesco Cecere,
  • Luigi Coppola,
  • Fabiana Cacace,
  • Peppino Mirabelli,
  • Francesco Paolo Tambaro

摘要

Background

Epigenetic dysregulation is a key therapeutic target in pediatric hematologic malignancies resistant to conventional chemotherapy, where allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. In this setting, hypomethylating agents (HMAs), such as azacitidine (AZA) and decitabine (DAC), are increasingly used as pre-transplant bridging strategies to reduce disease burden and enhance treatment sensitivity. Their integration with HSCT may improve pre-transplant remission rates, prolong complete remission, and increase the likelihood of durable disease control and cure. However, evidence in pediatric patients remains limited. Here, we performed a systematic review and pooled analysis to evaluate the efficacy of pre-HSCT epigenetic therapy in pediatric hematologic malignancies.

Results

A pooled analysis of seven studies of 87 pediatric patients including 51 Myelodysplastic Syndromes (MDS) and 36 Juvenile Myelomonocytic Leukemia (JMML) treated with DAC or AZA prior to HSCT was performed. Statistical analyses used chi-squared or Fisher’s exact tests for categorical variables and non-parametric tests for continuous variables, with correction for multiple comparisons. In MDS, Complete remission (CR) was achieved in 64.7% of patients and strongly associated with DAC, translating into improved post-HSCT survival compared to PD (84.2% vs. 42.8%). In JMML, partial remission (PR) and progressive disease (PD) predominated (47.2% and 41.7%, respectively), while CR was rare (11.1%); response was not associated with HMA type or genetic features, although older age correlated with PD. Comparative analysis confirmed superior responses in MDS (higher CR and SD) versus JMML, which showed higher PR and PD rates. PTPN11 mutations were significantly associated with multiple clinical variables, including treatment response.

Conclusions

Pre-transplant HMA therapy shows variable efficacy in pediatric myeloid malignancies. DAC induces rapid, deep responses in MDS, improving post-HSCT survival. JMML responds less, yet post-transplant survival remains favorable. Higher HMA responsiveness in MDS likely reflects predominant epigenetic dysregulation, whereas JMML is mainly driven by aberrant RAS/MAPK pathway activation. These results emphasize that pre-transplant strategies should be tailored to the specific biological and clinical context of each disease. However, their impact relative to upfront HSCT or conventional chemotherapy remains to be definitively determined.

Graphical abstract