Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

The impacts of total body irradiation on umbilical cord blood hematopoietic stem cell transplantation.

Background: Umbilical cord blood hematopoietic stem cells are commonly used for hematopoietic system reconstitution in recipients after umbilical cord blood transplantation (UCBT). However, the optimal conditioning regimen for UCBT remains a topic of debate. The exact impact of total body irradiation (TBI) as a part of conditioning regimens remains unknown.

Multi-institution analysis of tumor mutational burden and outcomes in pediatric central nervous system tumor patients.

Background: Pediatric central nervous system (CNS) tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision-making.

Methods: We conducted a retrospective analysis of pediatric patients (age <21) diagnosed with a primary CNS tumor at four upstate New York hospitals from 2008 to 2021.

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial.

Background: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma.

Methods: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction.

GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors.

ROS1 is a transmembrane receptor tyrosine kinase proto-oncogene that has been shown to have rearrangements with several genes in glioblastoma and other neoplasms, including intrachromosomal fusion with GOPC due to microdeletions at 6q22.1. ROS1 fusion events are important findings in these tumors, as they are potentially targetable alterations with newer tyrosine kinase inhibitors; however, whether these tumors represent a distinct entity remains unknown.

Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the "head-start" I and II clinical trials.

Background: The dismal outcome in children with high-grade brainstem gliomas (BSG) accentuates the need for effective therapeutic strategies. We investigated the role of intensive, including marrow-ablative, chemotherapy regimens in the treatment of young children with newly-diagnosed high-grade BSG.

Methods: Between 1991-and-2002, 15 eligible children less than 10 years of age with a diagnosis of high-grade BSG were treated on "Head-Start" I and II protocols (HSI and HSII).

Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries.

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma.

Background: Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets.

Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG.

Attributable costs of central line-associated bloodstream infections in a pediatric hematology/oncology population.

Background: Although several studies have estimated the attributable cost and length of stay (LOS) of central line-associated bloodstream infections (CLABSIs) in the pediatric intensive care unit setting, little is known about the attributable costs and LOS of CLABSIs in the vulnerable pediatric hematology/oncology population.

Methods: We studied a total of 1562 inpatient admissions for 291 pediatric hematology/oncology patients at a single tertiary care children's hospital in the mid-Atlantic region between January 2008 and May 2011. Costs were normalized to year 2011 dollars.

Reduction of central line-associated bloodstream infections in a pediatric hematology/oncology population.

This study reports the results of an initiative to reduce central line-associated bloodstream infections (CLABSIs) among pediatric hematology/oncology patients, a population at increased risk for CLABSI. The study design was a pre-post comparison of a series of specific interventions over 40 months. Logistic regression was used to determine if the risk of developing CLABSI decreased in the postintervention period, after controlling for covariates.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer.

Background: Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a "5-drug" oral regimen in children with recurrent or progressive cancer.

Procedure: Patients ≤21 years old with recurrent or progressive tumors were eligible.

Feasibility and parent satisfaction of a physical therapy intervention program for children with acute lymphoblastic leukemia in the first 6 months of medical treatment.

Background: Children with acute lymphoblastic leukemia (ALL) are at risk for developing musculoskeletal complications during and after their medical treatment. The objective of this study was to examine the feasibility of an in-hospital physical therapy- and home exercise program during the first four phases of medical treatment, for children with newly diagnosed ALL.

Procedure: Nine patients, between the ages of 2-14 years old were enrolled within 2 weeks of diagnosis in the study.

Physician referral frequency for physical therapy in children with acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) are at risk for developing musculoskeletal complications. Few studies have examined the role of physical therapy (PT) for addressing these complications. The study objective was to examine why and when in the medical treatment, children with ALL receive a referral to PT.

Epstein Barr virus induced lymphoma in a child with IPEX syndrome.

IPEX syndrome (immune deficiency, polyendocrinopathy, enteropathy, X-linked) is a disorder or regulatory T cell (Treg) function which can result in early death due to infection or complications related to autoimmunity. Therapeutic options for these patients can include allogeneic stem cell transplantation (SCT) or the use of immunosuppressive regimens to control the manifestations of autoimmunity. We report a patient with IPEX syndrome who was managed with rapamycin and subsequently developed EBV induced lymphoma.

Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): report of the Head Start I and II experience.

Background: Children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNET) have poor outcomes compared to medulloblastoma patients, despite similar treatments. In an effort to improve overall survival (OS) and event-free survival (EFS) and to decrease radiation exposure, the Head Start (HS) protocols treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy (ICHT) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR).

Procedures: Between 1991 and 2002, 43 children with sPNET were prospectively treated on two serial studies (HS I and II).

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children.

Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition.

Idiopathic thrombocytopenic purpura complicated by an intracranial hemorrhage secondary to an arteriovenous malformation.

Objective: To report a case of idiopathic thrombocytopenic purpura (ITP) complicated by an intracranial hemorrhage (ICH) in a child with a previously undiagnosed arteriovenous malformation.

Case: We describe a child with known ITP who developed a severe headache, was evaluated in an emergency department of a community hospital, and was found by computer tomography (CT) scan to have an ICH. Despite treatment with platelets, corticosteroids, and intravenous immunoglobulin, she subsequently developed an acute change in mental status.

Immunotherapy for Epstein-Barr virus-associated tumors.

Epstein-Barr Virus (EBV) is associated with a number of tumors, including lymphomas in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, patients with the acquired immunodeficiency syndrome (AIDS), Burkitt's lymphoma, as well as a subset of patients with nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). The types of latent EBV infections vary in these tumors, which influences the EBV antigens expressed and ultimately the immunogenicity of tumor cells. Not all EBV associated malignancies are directly related to altered cellular immunity, as is the case with EBV induced lymphoproliferations in immunocompromised patients.

Precursor B-cell lymphoblastic lymphoma presenting as an orbital mass.

A previously healthy 12-year-old boy presented with acute onset of proptosis of his left eye. CT scan demonstrated a mass involving the left orbit, left maxillary sinus, and left ethmoid sinus with extension through the cribriform plate into the anterior cranial fossa. Incisional biopsy of the mass revealed a precursor B-cell lymphoblastic lymphoma.