Cardiovascular Complications of Immune Effector Cell Therapies in Pediatric Hematological and Solid Tumors.

Background: Immune effector cell (IEC) therapies, including chimeric antigen receptor (CAR)-modified T-cell therapy, have shown efficacy in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to cardiovascular decompensation due to systemic inflammation. Data are limited regarding cardiovascular adverse effects in children.

Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15.

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15).

Indications and Outcomes for Tracheostomies in Pediatric Oncology Patients-A Single Center Study.

Background: Children with cancer face a high risk of complications including prolonged mechanical ventilation requiring tracheostomies. While tracheostomies have been demonstrated to be a generally safe procedure, there remain significant rare complications and a paucity of literature addressing outcomes specifically for pediatric patients with cancer. The objective of this study was to characterize pediatric patients with cancer who underwent tracheostomies and describe their indications and outcomes for length of stay, decannulation, and complications.

Cerebral Sinus Venous Thrombosis in Pediatric Acute Lymphoblastic Leukemia: Incidence, Clinical Characteristics, and Long-term Neurologic Outcomes.

Objective: To describe the incidence, clinical characteristics, and long-term outcomes of cerebral sinus venous thrombosis in children with acute lymphoblastic leukemia.

Methods: This was a retrospective cohort study comprising pediatric patients with newly diagnosed or first-relapse acute lymphoblastic leukemia who developed cerebral sinus venous thrombosis at Texas Children's Hospital from 2002 to 2019.

Results: Nineteen cases (1.

The Pathology of Pulmonary Disease After Pediatric Hematopoietic Stem Cell Transplantation.

Pulmonary complications continue to cause significant morbidity and mortality in posthematopoietic stem cell transplantation (HSCT) settings. The histopathology of pulmonary diseases in the post-HSCT context is poorly characterized, especially in the pediatric population. We sought to characterize the pathologic spectrum of pulmonary disease post-HSCT in a pediatric cohort.

Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort, 2009-2021.

Objective: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO).

Design: Multicenter, retrospective study.

Setting: Sixteen PICUs in the United States and Israel.

Eculizumab for management of hyperhemolysis syndrome in pediatric patients with sickle cell disease: A single-center case series.

Chronic hemolytic anemia and vascular occlusion are hallmarks of sickle cell disease (SCD). Blood transfusions are critical for supportive and preventive management of SCD complications. Patients with SCD are at risk for hyperhemolysis syndrome (HHS), a subtype of delayed hemolytic transfusion reactions.

Retrospective analysis of veno-occlusive disease/sinusoidal obstruction syndrome in paediatric patients undergoing hematopoietic cell transplantation -a multicentre study.

Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear.

Hematopoietic stem cell transplantation for B-thalassemia major with alemtuzumab.

While matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for transfusion-dependent beta-thalassemia (TDT), the use of alternative sources has increased, resulting in the exploration of novel transplant-conditioning regimens to reduce the contribution of graft-versus-host disease (GVHD) and graft failure (GF) to transplant-related morbidity and mortality. Alemtuzumab is a CD52 monoclonal antibody that has been successfully incorporated into myeloablative conditioning regimens for other hematologic conditions, yet there have been limited studies regarding the use of alemtuzumab in HSCT for TDT. The purpose of this study was to evaluate engraftment, incidence of GVHD, and transplant related morbidity and mortality in patients with TDT who received alemtuzumab in addition to standard busulfan-based conditioning.

Prospective Clinical and Biomarker Validation of the American Society for Transplantation and Cellular Therapy Consensus Definition for Transplantation-Associated Thrombotic Microangiopathy.

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition.

Multi-center retrospective study of children with sickle cell disease admitted to pediatric intensive care units in the United States.

Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database.

Pulmonary Histopathologic Findings in Pediatric Patients After Hematopoietic Stem Cell Transplantation: An Autopsy Study.

Background: Pathologic characterization of pulmonary complications following hematopoietic stem cell transplantation (HSCT) is limited. We describe lung findings in pediatric patients who died following HSCT and attempt to identify potential clinical associations.

Methods: Pathology databases at Texas Children's Hospital and the Children's Hospital of Philadelphia were queried (2013-2018 CHOP and 2017-2018 TCH).

Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival.

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy.

A multicenter study of ICU resource utilization in pediatric, adolescent and young adult patients post CAR-T therapy.

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).

Rituximab as adjunctive therapy to BEAM conditioning for autologous stem cell transplantation in Hodgkin lymphoma.

While high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) leads to improved disease-free survival (DFS) for children and adults with relapsed/refractory Hodgkin lymphoma (HL), relapse remains the most frequent cause of mortality post-transplant. Rituximab has been successfully incorporated into regimens for other B-cell lymphomas, yet there have been limited studies of rituximab in HL patients. We hypothesized that adding rituximab to BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning would reduce relapse risk in HL patients post-transplant.

Multicenter Experience of Hematopoietic Stem Cell Transplantation in WHIM Syndrome.

Purpose: WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a rare disease, caused by CXCR4 gene mutations, which incorporates features of combined immunodeficiency, congenital neutropenia, and a predisposition to human papillomavirus infection. Established conventional treatment for WHIM syndrome does not fully prevent infectious complications in these patients. Only single case reports of hematopoietic stem cell transplantation (HSCT) efficacy in WHIM have been published.

Gastric Adenocarcinoma in the Setting of IPEX Syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked disorder caused by a loss of function mutation in the gene. It manifests early in infancy with clinical symptoms including autoimmune enteropathy, type 1 diabetes mellitus, and eczema. While aberrant expression has been associated with several types of cancer, little is known regarding the risk of cancer in patients with IPEX harboring the characteristic mutation.

Expansion of germline RPS20 mutation phenotype to include Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a ribosomopathy of variable expressivity and penetrance characterized by red cell aplasia, congenital anomalies, and predisposition to certain cancers, including early-onset colorectal cancer (CRC). DBA is primarily caused by a dominant mutation of a ribosomal protein (RP) gene, although approximately 20% of patients remain genetically uncharacterized despite exome sequencing and copy number analysis. Although somatic loss-of-function mutations in RP genes have been reported in sporadic cancers, with the exceptions of 5q-myelodysplastic syndrome (RPS14) and microsatellite unstable CRC (RPL22), these cancers are not enriched in DBA.

Work efficiency improvement of >90% after implementation of an annual inpatient blood products administration consent form.

Paediatric haematology, oncology and bone marrow transplant (BMT) patients frequently require transfusion of blood products. Our institution required a new transfusion consent be obtained every admission. The objectives of this project were to: revise inpatient blood products consent form to be valid for 1 year, decrease provider time spent consenting from 15 to <5 min per admission, and improve provider frustration with the consent process.

Epilepsy surgery in a developing country (Lebanon): ten years experience and predictors of outcome.

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%).