Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.

Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing.

Bevacizumab, With Sorafenib and Cyclophosphamide Provides Clinical Benefit for Recurrent or Refractory Osseous Sarcomas in Children and Young Adults.

Objective: Children and adolescents with recurrent and metastatic solid tumors have a poor outcome. A previous phase 1 study (ANGIO1) targeting angiogenesis with bevacizumab, sorafenib, and cyclophosphamide, demonstrated a signal of activity in a subset of patients. Here we report the results of a cohort of pediatric and young adult patients treated at the recommended phase 2 doses.

Relapsed acute myeloid leukemia in children and adolescents: current treatment options and future strategies.

Pediatric acute myeloid leukemia (AML) develops from clonal expansion of hematopoietic precursor cells and is characterized by morphologic and cytomolecular heterogeneity. Although the past 40 years have seen significant improvements in overall survival, the prevailing treatment challenges in pediatric AML are the prevention of relapse and the management of relapsed disease. Approximately 25% of children and adolescents with AML suffer disease relapse and face a poor prognosis.

CPX-351 induces remission in newly diagnosed pediatric secondary myeloid malignancies.

Secondary myelodysplastic syndromes and acute myeloid leukemia (sMDS/AML) are rare in children and adolescents and have a dismal prognosis. The mainstay therapy is hematopoietic cell transplantation (HCT), but there has been no innovation in cytoreductive regimens. CP X-351, a fixed 5:1 molar ratio of liposomal cytarabine to daunorubicin, has shown favorable safety and efficacy in elderly individuals with secondary AML and children with relapsed de novo AML.

Clinical and biological aspects of myeloid leukemia in Down syndrome.

Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal myelopoiesis (TAM), which is self-limited expansion of fetal liver-derived megakaryocyte progenitors. An array of international studies has led to consensus in treating ML-DS with reduced-intensity chemotherapy, leading to excellent outcomes.

Activity of venetoclax against relapsed acute undifferentiated leukemia.

Acute undifferentiated leukemia is a rare hematologic malignancy with a poor prognosis. Venetoclax was highly active in two patients with relapsed acute undifferentiated leukemia and should be studied further.

Prehospital personnel discretion pediatric trauma team activations: Too much of a good thing?

Purpose: Trauma team activation is essential to provide rapid assessment of injured patients, however excessive utilization can overburden systems. We aimed to identify predictors of over triage and evaluate impact of prehospital personal discretion trauma activations on the over triage rate.

Methods: Retrospective comparative study of pediatric trauma patients (<18 years) evaluated after activation of the trauma team to those evaluated as a trauma consult treated between 2010 and 2013.

Allogeneic CAR Cell Therapy-More Than a Pipe Dream.

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics.

Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery.

Background: Immunotherapy with chimeric antigen receptor (CAR) T cells is actively being explored for pediatric brain tumors in preclinical models and early phase clinical studies. At present, it is unclear which CAR target antigens are consistently expressed across different pediatric brain tumor types. In addition, the extent of HLA class I expression is unknown, which is critical for tumor recognition by conventional αβTCR T cells.

Induction Chemotherapy With an Anti-GD2 Monoclonal Antibody (Dinutuximab) and Cytokines in Children With Newly Diagnosed High-risk Neuroblastoma: A Case Series.

Although outcomes for patients with high-risk neuroblastoma improved after the addition of a chimeric anti-GD2 monoclonal antibody (dinutuximab) as treatment for minimal residual disease, nearly half of these patients die of disease. Recent studies demonstrated efficacy of the combination of chemotherapy with anti-GD2 mAb in patients with relapsed or newly diagnosed disease. This retrospective case series describes 6 patients treated at St Jude Children's Research Hospital with an induction regimen containing dinutuximab and chemotherapy, followed by consolidation and postconsolidation therapy.

A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib.

Infantile fibrosarcoma (IFS) is a rare pediatric cancer that typically presents early in life. Surgical resection is commonly curative; however, resection is sometimes not possible requiring additional multimodal treatment. IFS commonly harbors a fusion in one of the neurotrophic receptor tyrosine kinase (NTRK) genes.

Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours.

Background: Angiogenesis is critical for tumour growth and metastasis. Dual inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors suppresses angiogenesis. This expansion cohort of a phase I study targeted angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with recurrent solid tumours.

SDF1-a facilitates Lin-/Sca1+ cell homing following murine experimental cerebral ischemia.

Background: Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized.

Methods: Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin-/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade.

Utilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion.

Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain(1-3). This technique can be performed in many locations overlying the rat cerebrum, but is most easily carried out by creating a craniectomy over the readily accessible frontal or parietal bones. Most frequently, we have used this technique in combination with the endothelin-1 middle cerebral artery occlusion model of ischemic stroke to quantify the changes in middle cerebral artery vessel diameter that occur with injection of endothelin-1 into the brain parenchyma adjacent to the proximal MCA(4, 5).

Endothelin-1 induced middle cerebral artery occlusion model for ischemic stroke with laser Doppler flowmetry guidance in rat.

Stroke is the number one cause of disability and third leading cause of death in the world, costing an estimated $70 billion in the United States in 2009. Several models of cerebral ischemia have been developed to mimic the human condition of stroke. It has been suggested that up to 80% of all strokes result from ischemic damage in the middle cerebral artery (MCA) area.

Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface.

Most contemporary biomaterial designs for osteochondral regeneration utilize monolithic, biphasic, or even multiphasic constructs. We have introduced a microsphere-based approach to create a continuous gradient in both material composition and encapsulated growth factors. The gradients were fabricated by filling a cylindrical mold with opposing gradients of two different types of poly(D,L-lactic-co-glycolic acid) microspheres.