Insights into Pediatric GATA2-Related MDS: Unveiling Challenges in Clinical Practice

Background: GATA2-related myelodysplastic syndrome (GATA2-MDS) is a unique predisposition syndrome with a high risk of leukemic transformation. This systematic review synthesizes current literature and presents two illustrative pediatric GATA2-MDS cases. Methods: Data retrieval from eight cohort and case–control studies provides comprehensive analysis on disease features, diagnostic complexities, management, and outcomes related to hematopoietic stem cell transplantation (HSCT) in GATA2-related myeloid malignancies. Additionally, two pediatric cases are included to exemplify clinical and therapeutic challenges in real-world setting. Results: The literature data demonstrates high incidence of monosomy 7, and recurrent infections as the most common clinical feature, followed by immunodeficiency and lymphedema. Prognosis clearly worsens with age and HSCT remains the only curative treatment. GATA2 patients undergoing HSCT experience high rates of graft versus host disease (GvHD) as well as unique neurological, thrombotic, and infectious complications. Transplant-related mortality (TRM) is linked to GvHD and infections. Post-transplant cyclophosphamide (PT/Cy) strategies seem to improve survival by reducing GvHD incidence. Overall survival (OS) remains variable across groups. The first case presents rapid disease progression to pulmonary alveolar proteinosis (PAP) and leukemic transformation, further developing severe HSCT complications. The second case addresses novel GATA2 mutation and raises concerns regarding alternative prophylactic and therapeutic strategies in transplant setting. Conclusions: Collaborative efforts aim to enhance understandings of GATA2-related myeloid malignancies and guide towards more effective management approaches.