FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin) with venetoclax shows promise as frontline pediatric acute myeloid leukemia therapy. In 12 patients treated at MD Anderson, most achieved remission with good early survival outcomes, and many proceeded to transplant. Common toxicities included cytopenias, comparable to previous regimens.

A 5-year-old female with sickle cell disease (SCD) (Hb SS) and poor compliance with hydroxyurea (HU) presented with a decline in hemoglobin (Hb), splenomegaly, and vaso-occlusive crisis. All of which become overlapping clinical features of different complications of SCD, including delayed hemolytic transfusion reaction (DHTR), and warm autoimmune hemolytic anemia (wAIHA). This patient’s initial presentation was with an orbital bone infarct for which she received an Rh/Kell antigens-unmatched transfusion. Because of subsequent alloimmunization with anti-D, anti-C, anti-E, and nonspecific IgG antibodies, she was started on a chronic transfusion regimen. At follow-up, she was noted to have splenomegaly and critically low Hb levels. She was then found to have developed wAIHA, splenic sequestration, and hyperhemolysis syndrome/possible DHTR. Through multidisciplinary decision-making, she was treated with intravenous immunoglobulin, methylprednisolone, and rituximab to stabilize her Hb and manage splenic sequestration to then allow for fully phenotypically matched red blood cells’ transfusion. Her last Hb during the admission was 7.8 g/dL. At this point, splenectomy was done in a safer context as definitive treatment for recurrent sequestration and immune hemolysis. This case highlights several important aspects of the care of patients with SCD, including multiple complications, treatment, and the importance of multidisciplinary coordination in high-risk or complex cases.

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system. Case Presentation: We present the case of an eight-month-old infant with influenza A(H1N1) who presented with seizures, hepatosplenomegaly, cytopenias, and markedly elevated levels of ferritin, IL-18, and CXCL9, raising concern for HLH. Despite initiation of HLH-directed and antiviral therapy, she succumbed to cardiorespiratory failure. Genetic testing revealed heterozygous variants in LYST and NLRC4, suggesting a potential genetic predisposition. Conclusions: This case underscores the challenge of distinguishing primary from secondary HLH and highlights the importance of balancing aggressive immunosuppression with infection control. Early genetic and cytokine profiling may assist in guiding personalized treatment strategies, enabling targeted interventions that avoid excessive immunosuppressive treatment in cases of reactive hyperinflammation while facilitating timely escalation of therapy in true or refractory HLH.

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where “one-size-fits-all” chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on shaping the therapeutic approach, including the integration of targeted therapies such as FLT3 and menin inhibitors into frontline therapy. Furthermore, pediatric AML treatment options are being driven by recent discoveries in adult AML, broadening their clinical trials to include pediatric patients, in part due to the RACE for Children Act that went into effect in August 2020. This review identifies the most prevalent high-risk cytogenetic lesions in pediatric AML, emphasizing their incidence, prognostic significance, and implications for clinical management. By synthesizing current research on these key genetic abnormalities and their associated therapies, we aim to provide an updated perspective on the evolving landscape of high-risk pediatric AML management that can then lead to the establishment of an agile framework to rapidly evaluate, approve, and deploy novel agents.