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Purpose: Brentuximab vedotin (BV) incorporation into frontline chemotherapy regimens improved outcomes for classic Hodgkin lymphoma (cHL). The shared mechanism of action of BV and vinca alkaloids as microtubulin inhibitors increased the potential risk of chemotherapy-induced peripheral neuropathy (CIPN). Rates of CIPN and use of protocol-stipulated dose modifications of a microtubulin inhibitor were examined on the Children's Oncology Group AHOD1331 study, which compared BV, doxorubicin, vincristine (VCR), etoposide, prednisone, cyclophosphamide (BV-AVE-PC; BV arm) with bleomycin containing doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC; standard arm) in patients with high-risk cHL ages 2-21 years., Methods: AHOD1331 required clinician grading and reporting of ≥grade 2 CIPN. Protocol-stipulated dose modifications of VCR preceded modification of BV for ≥grade 2 CIPN in the BV arm, but only required modification of VCR for ≥grade 3 in the standard arm. Outcomes included CIPN rates, dose modification of microtubulin inhibitors by study arm, clinical factors associated with dose modifications, and event-free survival (EFS) by the presence of dose modification., Results: Among the 582 patients who began protocol therapy, 112 developed ≥grade 2 CIPN. Cumulative incidence of CIPN did not differ by study arm (19.2 v 19.8%, P = .91). CIPN dose modifications occurred more frequently in the BV arm (9.5% v 2.8%, P = .001); however, most patients with CIPN on the BV arm received full-dose BV. EFS did not differ by the presence of dose modifications after accounting for study arm, age, sex, and stage, although older age was significantly associated with the risk of VCR dose modifications for CIPN., Conclusion: A staged dose modification plan for vinca alkaloids and BV as administered in AHOD1331 minimized the effect of incorporating a second microtubulin inhibitor on CIPN without compromising treatment efficacy in the BV arm.

Hodgkin lymphoma (HL) occurs throughout the lifespan but is one of the most common cancers in adolescents and young adults (AYA; 15-39 years). HL has become a highly curable disease with survival rates surpassing 90%, including patients with high-risk and advanced stage disease. Unfortunately, intensive treatment carries a risk of short- and long-term toxicity. Given the decades pediatric HL survivors are expected to live after treatment, the pediatric approach to treatment has focused on improving the therapeutic index through response adapted treatment and more recently the incorporation of novel agents. The efforts of pediatric and medical oncologists in research and clinical trial development have long occurred in parallel, but recent efforts have laid the foundation for collaboration with the goal of standardizing AYA care and allowing earlier incorporation of novel therapy for younger patients. This review focuses on the evolution of the management of pediatric HL including epidemiology, biology, and approaches to upfront and salvage treatment regimens., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mallorie B. Heneghan reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Jennifer A. Belsky reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Christopher J. Forlenza reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: As society continues to advance in technology, it is important to address how this advancement can impact and enhance patient care. The purpose of this review is to identify patient-centered technology currently available for adult and pediatric patients with and those having survived hematologic malignancies. Given that patients with hematologic malignancies often have to adhere to strenuous medication regimens, coordinate care with many different providers, manage symptoms associated with treatment, and manage late effects associated with survivorship, they would benefit greatly from patient-centered technology aimed at decreasing these burdens., Recent Findings: This review found various available digital interventions for this patient population and focuses on an overview of commercially available smartphone applications, patient portals, and technology for remote monitoring. In summary, many digital interventions exist for use in the medical care of oncology patients. The incorporation of these interventions can allow for more personalized medical care, better organization of treatment plans by caregivers at home, and easy delivery of accurate medical information., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML)., Design: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States., Exposure: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity., Outcome: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey., Result: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction., Conclusions: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Sickle cell disease (SCD) affects more than 100,000 Americans, with complications such as pain episodes and acute chest syndrome. Despite the efficacy of hydroxyurea in reducing these complications, adherence remains low. Study objectives were to examine barriers to hydroxyurea adherence, and to evaluate the relationship between barriers and their impact on adherence., Methods: In this cross-sectional study, patients with SCD and their caregivers were enrolled if they were taking hydroxyurea. Study measures included demographics, self-report of adherence using visual analog scale (VAS), and the Disease Management and Barriers Interview (DMI)-SCD. The DMI-SCD was mapped to the Capability, Opportunity, Motivation, and Behavior (COM-B) model., Results: Forty-eight caregivers (females 83%, median age 38 [34-43]) and 19 patients (male 53%, median age 15 [13.5-18]) participated. Using VAS, many patients (63%) reported low hydroxyurea adherence, while most caregivers (75%) reported high adherence. Caregivers endorsed barriers across multiple COM-B components, with physical opportunity (e.g., cost) and reflective motivation (e.g., SCD perceptions) being the most identified categories (48% and 42%), respectively. Patients' most identified barriers included psychological capability (e.g., forgetfulness) and reflective motivation (84% and 68%), respectively. Patients' and caregivers' VAS scores negatively correlated with the number of barriers (r s  = -.53, p = .01; r s  = -.28, p = .05) and COM-B categories (r s  = -.51, p = .02; r s  = -.35, p = .01), respectively, suggesting lower adherence with more endorsed barriers., Conclusions: Fewer barriers to hydroxyurea adherence were associated with higher adherence. Understanding barriers to adherence is essential to develop tailored interventions aimed at improving adherence., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2-3 years of a prolonged maintenance phase composed of oral chemotherapies. Adherence to these medications is critical to achieving good outcomes. However, adherence is difficult to determine, as there is currently no consensus on measures of adherence or criteria to determine nonadherence. Furthermore, there have been few studies in pediatric B-ALL describing factors associated with nonadherence. Thus, we performed a systematic review of literature on oral chemotherapy adherence during maintenance therapy in ALL following PRISMA guidelines. Published studies demonstrated various objective and subjective methods of assessing adherence without generalizable definitions of nonadherence. However, the results of these studies suggested that nonadherence to oral maintenance chemotherapy was associated with increased risk of relapse. Future studies of B-ALL therapy should utilize a uniform assessment of adherence and definitions of nonadherence to better determine the impact of nonadherence on B-ALL outcomes and identify predictors of nonadherence that could yield targets for adherence improving interventions.

Objective: Patients facing an advanced cancer diagnosis require clear communication with their clinicians. Technology has been utilized in many different capacities to navigate communication in cancer care, but few authors examine the specific areas of communication from a theoretical perspective. The purpose of this literature review was to (1) identify articles focused on technology-based communication strategies to improve health outcomes in individuals with advanced cancer, and (2) using Epstein and Street's framework, identify areas in which technology-based communication has been used to improve health outcomes, and (3) identify gaps that exist in technology-based communication care in patients with advanced cancer., Methods: A systematic search was conducted which returned 446 articles. Using Epstein and Street's 2007 framework, the final sample was 39., Results: Nine clinical trials, 29 observational studies, and 1 case study were identified. The articles were categorized into one area within Epstein and Street's areas of communication. Many of the articles examined the patient's and provider's acceptability and feasibility of technology-based methods of communication, while other articles examined their efficacy., Conclusions: While research studies were identified in each of the areas of communication, the majority of technology-based communication strategies were focused on the exchange of information between patients and their providers. Further research and the development of technology-based communication interventions assessed through clinical trials are needed in the areas of healing relationships and making decisions in cancer care. Additionally, the communication strategies found effective at improving health outcomes in advanced cancer should begin implementation into clinical practice, therefore reaching more patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Suboptimal adherence to 6-mercaptopurine (6-MP) is prevalent in pediatric acute lymphoblastic leukemia (ALL) and associated with increased risk of relapse. Rapid uptake of personal technology makes mobile health (mHealth) an attractive platform to promote adherence., Objective: Study objectives were to examine access to mobile technology and preferences for an mHealth intervention to improve medication adherence in pediatric ALL., Methods: A cross-sectional survey was administered in oncology clinic to parents of children with ALL as well as adolescents and young adults (AYAs) with ALL receiving maintenance chemotherapy., Results: A total of 49 parents (median age [IQR] 39 [33-42] years; female 76% [37/49]) and 15 patients (median age [IQR] 17 [16-19]; male 80% [12/15]) participated. All parents and AYAs owned electronic tablets, smartphones, or both. Parents' most endorsed mHealth app features included a list of medications (71%, 35/49), information about 6-MP (71%, 35/49), refill reminders (71%, 35/49), and reminders to take 6-MP (71%, 35/49). AYAs' most endorsed features included refill reminders (73%, 11/15), reminders to take 6-MP (73%, 11/15), and tracking 6-MP (73%, 11/15)., Conclusions: Parents and AYAs reported ubiquitous access to mobile technology and strong interest in multiple adherence-specific mHealth app features. Parents and AYAs provided valuable insight into preferred features for a multifunctional behavioral intervention (mHealth app) to promote medication adherence in pediatric ALL., (©Mallorie B Heneghan, Tasmeen Hussain, Leonardo Barrera, Stephanie W Cai, Maureen Haugen, Elaine Morgan, Jenna Rossoff, Joanna Weinstein, Nobuko Hijiya, David Cella, Sherif M Badawy. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 18.02.2021.)

Background: Adherence to oral chemotherapy, including 6-mercaptopurine (6-MP), is suboptimal in pediatric acute lymphoblastic leukemia (ALL), which is associated with increased risk of relapse. Study objectives were to examine self-reported adherence to 6-MP and related barriers to adherence, mapped to the capability, opportunity, motivation, and behavior (COM-B) model for behavior change., Procedure: Forty-nine parents (median, 39 years old; 76% females) and 15 patients (median, 17 years old, 20% females) completed the study survey., Results: Suboptimal adherence was reported in 43% of parents and 73% of patients. Most parents and patients (80% and 90%, respectively) reported ≥1 adherence barrier. Parents reported difficulty helping their child meet others with ALL (43%), contacting community organizations (39%), and meeting other parents (37%). Patients reported difficulty finding out what their medications are (40%), finding out what 6-MP does (47%), and meeting other patients (40%). Using the COM-B, we found that parents and patients endorsed barriers in multiple components, especially physical (55%, 67%) and social opportunity (56%, 47%), highlighting that barriers to adherence may be multifaceted., Conclusions: Our results suggest that parents and patients with ALL face various prevalent barriers to medication adherence and provide insight into the development of behavioral interventions focused on promoting adherence, which is essential to prevent relapse and optimize health outcomes in ALL., (© 2020 Wiley Periodicals, Inc.)

Background: Unintentional medication nonadherence is common and has been associated with poor health outcomes and increased health care costs. Earlier research demonstrated a relationship between habit strength and medication adherence. Previous research also examined a habit's direct effect on adherence and how habit interacts with more conscious factors to influence or overrule them. However, the relationship between habit and adherence and the role of habit-based mobile health (mHealth) interventions remain unclear., Objective: This review aimed to systematically evaluate the most recent evidence for habit strength, medication adherence, and habit-based mHealth interventions across chronic medical conditions., Methods: A keyword search with combinations of the terms habit, habit strength, habit index, medication adherence, and medication compliance was conducted on the PubMed database. After duplicates were removed, two authors conducted independent abstract and full-text screening. The guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed when reporting evidence across the included and reviewed studies., Results: Of the 687 records examined, 11 met the predefined inclusion criteria and were finalized for data extraction, grading, and synthesis. Most included studies (6/11, 55%) were cross-sectional and used a theoretical model (8/11, 73%). The majority of studies measured habit strength using the self-report habit index and self-report behavioral automaticity index (9/11, 82%). Habit strength was positively correlated with medication adherence in most studies (10/11, 91%). Habit mediated the effects of self-efficacy on medication adherence (1/11, 9%), and social norms moderated the effects of habit strength on medication adherence (1/11, 9%). Habit strength also moderated the effects of poor mental health symptoms and medication adherence (1/11, 9%). None of the included studies reported on using or proposing a habit-based mHealth behavioral intervention to promote medication adherence., Conclusions: Habit strength was strongly correlated with medication adherence, and stronger habit was associated with higher medication adherence rates, regardless of the theoretical model and/or guiding framework. Habit-based interventions should be used to increase medication adherence, and these interventions could leverage widely available mobile technology tools such as mobile apps or text messaging, and existing routines., (©Sherif M Badawy, Richa Shah, Usman Beg, Mallorie B Heneghan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.04.2020.)

Objectives: The primary objectives were to (a) identify current published research in electronic health (eHealth) and mobile health (mHealth) interventions for youth undergoing cancer treatment and child, adolescent, and young adult survivors of childhood cancer and (b) critically appraise the current scientific evidence on their effectiveness and efficacy. As an exploratory aim, we identified pediatric cancer patients' and survivors' perceptions, attitudes, and concerns related to eHealth and mHealth interventions., Methods: A comprehensive search of the literature was performed to identify peer-reviewed journal articles that included the use of mHealth and eHealth interventions among youth receiving active cancer treatment and survivors of childhood cancer through the age range of childhood to young adulthood (mean age 21 years or younger at the time of diagnosis; mean age 39 years or younger at the time of intervention). The search was conducted via six electronic databases: PubMed, CINAHL, EMBASE, PsycINFO, IEEEXplore and the Cochrane Library., Results: Of the 1879 potential records examined, 21 met criteria for inclusion for a total of 1506 participants. Of the investigations included, 13 were randomized controlled trials, and eight were nonrandomized studies. Findings demonstrated feasibility as well as acceptability with these approaches. Evidence of efficacy for interventions targeting emotional distress, health behaviors, health outcomes, and neurocognitive functioning was mixed., Conclusions: Given the growing evidence of efficacy, coupled with increasing access to digital technologies, eHealth and mHealth may serve an important role in improving mental and physical health outcomes of youth undergoing cancer treatment and child, adolescent, and young adult survivors of childhood cancer., (© 2019 John Wiley & Sons, Ltd.)

The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.

Background: Cure rates for acute lymphoblastic leukemia (ALL) have improved, but as therapy has intensified, the burden of osteonecrosis (ON) has increased. Limited data exist regarding surgical interventions for pediatric ALL patients with ON., Materials and Methods: A multi-center cohort of children with newly diagnosed ALL was established with Pediatric Health Information System (PHIS) data from 43 freestanding children's hospitals from 1999 to 2011. Patients with ON identified by International Classification of Diseases, Ninth Revision (ICD-9) code were followed for up to 5 years after index ALL admission for the presence of ON-associated orthopedic surgical procedures., Results: A cohort of 10,729 ALL patients was assembled, of which 242 (2.33%) were identified with an ICD-9 code for ON within 5 years of ALL diagnosis. Fifty-five patients (22.7%) with ON underwent orthopedic surgical intervention aimed at joint preservation (82%) or replacement (18%) with substantial practice variation by hospital in both the rate and type of surgical intervention. The majority of patients had surgical procedures while receiving maintenance therapy. None of the patients undergoing surgical intervention required intensive care unit-level care within 14 days of surgery, and there was no associated in-hospital mortality., Conclusions: No standard of care exists for treatment of ALL-associated ON. While considerable practice variation exists, surgical intervention appears relatively safe., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells., Methodology/principal Findings: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas., Conclusion: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.