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.

Impact of undernutrition on the pharmacokinetics of chemotherapy in children with cancer: A systematic review.

Objectives: This systematic review provides an overview of the effect of undernutrition on the pharmacokinetics of chemotherapy in children with cancer.

Methods: PubMed, Embase, and Cochrane were searched to identify eligible studies. This study uses the definition for undernutrition from the World Health Organization and the Gomez classification.

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse.

Purpose: Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab.

Patients And Methods: After block 1 reinduction, patients age 1-30 years with LR first relapse of B-ALL were randomly assigned to block 2/block 3/two continuation chemotherapy cycles/maintenance (arm C) or block 2/two cycles of continuation chemotherapy intercalated with three blinatumomab blocks/maintenance (arm D).

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.

Algorithmic encoding of protected characteristics in chest X-ray disease detection models.

Background: It has been rightfully emphasized that the use of AI for clinical decision making could amplify health disparities. An algorithm may encode protected characteristics, and then use this information for making predictions due to undesirable correlations in the (historical) training data. It remains unclear how we can establish whether such information is actually used.

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.

Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia.

Background: Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML).

Methods: We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs.

Active label cleaning for improved dataset quality under resource constraints.

Imperfections in data annotation, known as label noise, are detrimental to the training of machine learning models and have a confounding effect on the assessment of model performance. Nevertheless, employing experts to remove label noise by fully re-annotating large datasets is infeasible in resource-constrained settings, such as healthcare. This work advocates for a data-driven approach to prioritising samples for re-annotation-which we term "active label cleaning".

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry.

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile.

Objective: To determine whether substituting blinatumomab for intensive chemotherapy in consolidation therapy would improve survival in children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL.

Blinatumomab use in pediatric ALL: Taking a BiTE out of preparation, administration and toxicity challenges.

Blinatumomab is the first in its class bispecific T-cell engager monoclonal antibody, which binds to CD19 expressed on B-cells and CD3 expressed on T-cells, resulting in lysis of CD19-positive cells common in B-cell malignancies. Blinatumomab is Food and Drug Administration (FDA) approved for the treatment of adults and children with relapsed/refractory or minimal residual disease (MRD) positive precursor B-cell ALL (B-ALL). Despite impressive efficacy for the approved indications and favorable toxicity profile compared to standard-of-care chemotherapy, blinatumomab presents unique health-system challenges related to preparation, administration, toxicity monitoring and medication error prevention.

Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse.

Purpose: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

Methods: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2).

Training Variational Networks With Multidomain Simulations: Speed-of-Sound Image Reconstruction.

Speed-of-sound (SoS) has been shown as a potential biomarker for breast cancer imaging, successfully differentiating malignant tumors from benign ones. SoS images can be reconstructed from time-of-flight measurements from ultrasound images acquired using conventional handheld ultrasound transducers. Variational networks (VNs) have recently been shown to be a potential learning-based approach for optimizing inverse problems in image reconstruction.

Review of nutritional status, body composition, and effects of antineoplastic drug disposition.

The overall survival for children with cancer in high income countries is excellent. However, there are many disparities that may negatively affect survival, which are particularly problematic in low income countries, such as nutritional status at diagnosis and throughout therapy. Nutritional status as well as concomitant foods, supplements, and medications may play a role in overall exposure and response to chemotherapy.

Risk factors associated with delayed methotrexate clearance and increased toxicity in pediatric patients with osteosarcoma.

High-dose methotrexate (HD-MTX; 12 g/m ) is part of standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. We investigated the association between peak MTX levels (four-hour) and delayed MTX clearance or treatment toxicity.

Race and ethnicity: Not factors in the prescribing of hydrocodone and codeine-containing products in two pediatric emergency departments.

Objective: To describe the prescription of hydrocodone-containing products (HCPs) and codeine-containing products (CCPs) by patient and provider race and ethnicity at two pediatric emergency departments (EDs) before and after the US Drug Enforcement Administration (DEA) rescheduling of HCPs in 2014.

Design And Setting: The authors performed a secondary analysis of data describing the prescription of HCPs and CCPs for 6 months before and after the DEA rescheduling of HCPs in two academic, urban pediatric EDs.

Patients, Participants: The authors included all children for whom race and ethnicity data were available and who were prescribed HCPs or CCPs at the time of discharge from the ED during a 12-month period (n = 1,246).

Chemotherapy and Supportive Care Agents as Essential Medicines for Children With Cancer.

In resource-rich countries, 5-year survival rates for children with cancer approach 85%. This impressive statistic is largely the result of integrating research with clinical care. At the core of this endeavor are multiagent combination chemotherapy and supportive care agents (CASCA).

Efficacy of liposomal bupivacaine in pediatric patients undergoing spine surgery.

Background: Liposomal bupivacaine may be an option for reducing opioid utilization in pediatric scoliosis surgery. The use of liposomal bupivacaine in this patient population has not been previously described.

Methods: Patients who underwent posterior spinal fusion surgery at our institution from 2011-2016 were identified.

A phase 1 study of cabozantinib in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: Trial ADVL1211, a report from the Children's Oncology Group.

Background: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of cabozantinib in children with refractory or relapsed solid tumors.

Methods: Patients received cabozantinib tablets on a continuous dosing schedule in a rolling-six escalating phase 1 trial design. PK and PD studies were performed.

Using a Bedside Algorithm to Individually Dose High-dose Methotrexate for Patients at Risk for Toxicity.

We developed a bedside algorithm for individually adjusting the high-dose methotrexate (HDMTX) dose (5 g/m) given to patients with acute lymphoblastic leukemia at high risk for methotrexate toxicity. Data were reviewed for 8 patients receiving 21 cycles of HDMTX as per our algorithm. Eleven cycles began with 5 g/m, 10 cycles began with a preinfusion 20% to 25% dose reduction.