Adolescents and Young Adults With Sickle Cell Disease: Nociplastic Pain and Pain Catastrophizing as Predictors of Pain Interference and Opioid Consumption.

Objectives: Some patients with sickle cell disease (SCD) have features of nociplastic pain. While research suggests that many patients with nociplastic pain consume more opioids due to opioid nonresponsiveness, little is known about the impact of nociplastic pain and pain catastrophizing on opioid consumption and pain interference among adolescents and young adults (AYA) with SCD. The purpose of this study was to (1) characterize nociplastic pain and pain catastrophizing among AYA with SCD, and (2) determine whether these characterizations are associated with subsequent opioid consumption and pain interference 1 month after characterization.

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.

Ethical Perspectives of Chinese and United States Physicians at Initiation of a Research Collaborative.

Variances in perceived standards regarding research integrity appear to exist between China and the U.S. An established joint institute for translational and clinical research between one Chinese and one U.

Impact of Risk-Adapted Therapy for Pediatric Hodgkin Lymphoma on Risk of Long-Term Morbidity: A Report From the Childhood Cancer Survivor Study.

Purpose: To determine the incidence of serious chronic health conditions among survivors of pediatric Hodgkin lymphoma (HL), compare by era of therapy and by selected cancer therapies, and provide estimates of risks associated with contemporary therapy.

Methods: Assessing 2,996 5-year HL survivors in the Childhood Cancer Survivor Study diagnosed from 1970 to 1999, we examined the cumulative incidence of severe to fatal chronic conditions (grades 3-5) using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index. We used multivariable regression models to estimate hazard ratios (HRs) per decade and by key treatment exposures.

18F-2-fluoro-2-deoxyglucose uptake in white adipose tissue on pediatric oncologic positron emission tomography (PET)/computed tomography (CT).

Background: Altered biodistribution of [F-18]2-fluoro-2-deoxyglucose (FDG) is sometimes encountered in pediatric patients undergoing chemotherapy for lymphoma on post-induction positron emission tomography (PET) imaging. A characteristic pattern of increased FDG uptake in white adipose tissue can be seen, particularly in the buccal regions, body wall and gluteal regions, with a shift of radiotracer away from the blood pool and liver. This altered biodistribution has been attributed to effects of corticosteroids in pediatric and adult patients and is important to recognize because of its potential for limiting the diagnostic quality of the PET scan and interfering with therapeutic response assessment.

A single-center multidisciplinary approach to managing the global Erwinia asparaginase shortage.

The availability of Erwinia Asparaginase has been limited across the world due to manufacturing shortages or for some countries due to the high acquisition cost, putting patients at risk for inferior outcomes. This manuscript provides guidance on how to manage hypersensitivity reactions and utilize therapeutic drug monitoring (TDM) to conserve and limit Erwinia use. The clinical and financial impact of a multidisciplinary committee are also discussed.

Do Deauville Scores Improve the Clinical Utility of End-of-Therapy FDG PET Scans for Pediatric Hodgkin Lymphoma?

Objective: The purpose of this study was to evaluate the clinical utility of Deauville scores in interpretation of end-of-chemotherapy FDG PET scans.

Conclusion: Deauville scores improve the clinical utility of end-of-chemotherapy PET, as evidenced by an increase in positive predictive value to 72.7% from 44.

Ataxia Telangiectasia and Cancer Predisposition: Challenges in Management.

Immune dysregulation and predisposition to malignancies are critical comorbidities in children affected with ataxia telangiectasia. In addition, these children exhibit increased toxicity to conventional cancer therapy and dose reductions have been proposed to prevent life threatening adverse effects. These modifications to the treatment regimen may result in suboptimal outcomes for these patients.

Disclosing Study Information to Children and Adolescents: Is What They Want, What Their Parents Think They Want?

Objective: Despite the importance of child assent, there is little consensus on what information should be disclosed and what information is most important to children for decision-making. This study was designed to compare children's/adolescents' priorities for research information with the information parents believe is most important to their children.

Methods: Child-parent dyads completed separate and independent surveys regarding information (risks, benefits, etc) that they perceived to be most important to the child to make decisions about participating in a hypothetical randomized controlled trial.

The Ethics of Clinical Care and the Ethics of Clinical Research: Yin and Yang.

The Belmont Report's distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole exceeds the sum of its parts.

Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth.

Importance: Cancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging.

Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5).

Primary care for adult survivors of childhood cancer: medical needs and required strategies.

Provision of targeted care to the adult survivors of childhood cancer is a current need, likely to only increase in the future. The definition of the long-term effects of cancer, the magnitude of the treatment delivered, and the care required as a consequence fall within the domain of pediatric oncologists. The actual delivery of care including targeted follow-up and interventions, require the combined dedication and talents of pediatric oncologists working with adolescent medicine, internal medicine, medical-pediatrics, and family practice physicians to contribute by making this domain of care a priority and a collaborative goal, developing both an educational approach to and a structured care delivery model for the special needs of adult survivors of childhood cancer.

Measuring vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

Background: Vincristine-induced peripheral neuropathy (VIPN) is difficult to quantify in children.

Objective: The study objective was to examine the reliability, validity, and clinical feasibility of several VIPN measures for use in children with acute lymphoblastic leukemia.

Interventions/methods: Children (n = 65) aged 1 to 18 years receiving vincristine at 4 academic centers participated in the study.

Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group.

Purpose: In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007.

Patients And Methods: Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942.

Hospitalization rates among survivors of childhood cancer in the Childhood Cancer Survivor Study cohort.

Background: Chronic health conditions are common among long-term childhood cancer survivors, but hospitalization rates have not been reported. The objective of this study was to determine overall and cause-specific hospitalization rates among survivors of childhood cancer and compare rates to the U.S.

FDG PET imaging of childhood sarcomas.

Background: Positron-emission tomography (PET) imaging using [(18)F]fluorodeoxyglucose (FDG) is useful for detection, staging, and monitoring a variety of malignancies, including lymphoma, in adults, but its utility in sarcomas, especially soft tissue sarcomas (STS), in children and young adults is not clear.

Procedure: To evaluate the potential utility of FDG PET in the care of STS in children and young adults, we analyzed 46 PET scans in 25 patients acquired over 12 years. Scans were interpreted by two imaging physicians blinded to findings from other imaging studies and clinical information.

Plasma elevations of tumor necrosis factor-receptor-1 at day 7 postallogeneic transplant correlate with graft-versus-host disease severity and overall survival in pediatric patients.

Tumor necrosis factor-alpha (TNF-alpha) is known to play a role in the pathogenesis of graft-versus-host disease (GVHD), a cause of significant morbidity and treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). We measured the concentration of TNF-Receptor-1 (TNFR1) in the plasma of HCT recipients as a surrogate marker for TNF-alpha both prior to transplant and at day 7 in 82 children who underwent a myeloablative allogeneic HCT at the University of Michigan between 2000 and 2005. GVHD grade II-IV developed in 39% of patients at a median of 20 days after HCT.

Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival.

Acute graft-versus-host disease (GVHD) remains a significant cause of mortality after hematopoietic cell transplantation (HCT). Tumor necrosis factor-alpha (TNF-alpha) mediates GVHD by amplifying donor immune responses to host tissues and by direct toxicity to target organs. We measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-alpha in 438 recipients of myeloablative HCT before transplantation and at day 7 after transplantation.

Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is a principal cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). Standard therapy for GVHD, high-dose steroids, results in complete responses (CRs) in 35% of patients. Because tumor necrosis factor-alpha (TNFalpha) is an important effector of experimental GVHD, we treated patients with new-onset GVHD with steroids plus the TNFalpha inhibitor etanercept on a previously reported pilot trial (n = 20) and a phase 2 trial (n = 41).