Toxicity profile of high-dose methotrexate in young children with central nervous system tumors.

High-dose methotrexate (HD-MTX) is used in the treatment of children with central nervous system (CNS) tumors; however, toxicity information is limited. We characterized toxicities following 102 administrations of HD-MTX (4.6-13.

Optimizing early phase clinical trial washout periods: a report from the Therapeutic Advances in Childhood Leukemia and Lymphoma consortium.

Background: The National Cancer Institute (NCI) issued a 2021 memorandum adopting the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) task force recommendations to broaden clinical study eligibility criteria. They recommended that washout periods be eliminated for most prior cancer therapy and when required to utilize evidence- and/or rationale-based criteria. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium responded to this guidance.

Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium.

An Intracardiac Atrioventricular Vena Caval Mass: A Case Report.

Cardiac tumors (CTs) and intracardiac masses are rare, with an incidence of 1 per 2 million people annually. We present a case of an intracardiac mass where the patient exhibited progressive lower extremity swelling, night sweats, and diarrhea. Computed tomography of the chest with intravenous contrast revealed a sizable intracardiac mass with mixed attenuation and signs of metastatic lesions, suggesting a malignant process.

Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.

The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model-informed supportive care and optimal use of glucarpidase following the administration of high-dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.

Repurposing Atovaquone as a Therapeutic against Acute Myeloid Leukemia (AML): Combination with Conventional Chemotherapy Is Feasible and Well Tolerated.

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients.

Ethnic-specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high-dose methotrexate.

Background: High-dose methotrexate (HD-MTX; 5000 mg/m ) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL.

Sinusoidal Obstruction Syndrome of the Liver Associated With 6-Mercaptopurine During Maintenance in a Child With T-cell Acute Lymphoblastic Leukemia.

Sinusoidal obstruction syndrome (SOS) of the liver is a complication of chemotherapy most often encountered with hematopoietic stem cell transplant due to high-dose conditioning regimens, but it can also occur with regimens outside of the transplant setting. Mild-to-moderate SOS is a well-described 6-thioguanine toxicity; however, it has rarely been reported as secondary to 6-mercaptopurine, a related thiopurine. This report details a case of a 10-year-old male with T-cell acute lymphoblastic leukemia who developed severe SOS during maintenance therapy with 6-mercaptopurine, and a review of the related literature.

Lock-In Pixel CMOS Image Sensor for Time-Resolved Fluorescence Readout of Lateral-Flow Assays.

We present a CMOS image sensor (CIS) based time-resolved fluorescence (TRF) measurement system for filter-less, highly sensitive readout of lateral-flow assay (LFA) test strips. The CIS contains a 256 × 128 lock-in pixel (LIP) sensor array. Each pixel has a size of 10 μm × 10 μm and includes a photodiode acting as signal transducer.

Real-world experience in treating pediatric relapsed/refractory or therapy-related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium.

Current therapies for relapsed/refractory (R/R) pediatric myeloid neoplasms are inadequately effective. Real-world data (RWD) can improve care by augmenting traditional studies and include individuals not eligible for clinical trials. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium recently completed T2016-003, a phase 1 study of decitabine, vorinostat, fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in R/R acute myeloid leukemia (AML), which added epigenetic drugs to a cytotoxic backbone.

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium.

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475].

Temsirolimus combined with cyclophosphamide and etoposide for pediatric patients with relapsed/refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium trial (TACL 2014-001).

Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in acute lymphoblastic leukemia (ALL). The TACL2014-001 phase I trial of the mTOR inhibitor temsirolimus in combination with cyclophosphamide and etoposide was performed in children and adolescents with relapsed/refractory ALL. Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily on days 1-5.

Light Absorption Measurement With a CMOS Biochip for Quantitative Immunoassay Based Point-of-Care Applications.

We present a CMOS biochip-based photometer for quantitative immunoassay diagnostics. The photometer quantifies the concentration of antigens based on light absorption, which allows for a low-cost implementation without expensive optical components. We propose a light controller to lower the start-up and settling time of the light source to 30 seconds, to facilitate fast measurement starts, and to decrease the overall measurement times.

Do intravenous fluid substitutions influence methotrexate clearance? An unanticipated impact of an intravenous sodium bicarbonate drug shortage.

Background: National drug shortages of essential medications for childhood cancer have increasingly posed a challenge in the treatment of patients. The efficacy of standardized supportive care practices to avoid treatment-related toxicities may be limited during these drug shortages. High-dose methotrexate (HDMTX) plays a critical role in modern treatment protocols for acute lymphoblastic leukemia and requires stringent supportive care measures to mitigate toxicity.

Rates and risk factors associated with 90-day readmission following cervical spine fusion surgery: analysis of the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry.

Background Context: Hospital readmission rates are an increasingly important focus. Identifying patients at risk for readmission can help decrease those rates and thus decrease the overall cost of care.

Purpose: We sought to report the rates and the risk factors associated with 90-day hospital readmission after degenerative cervical spine surgery via either an anterior or posterior approach.