Feasibility pilot trial of a tailored medication adherence-promotion intervention for adolescents and young adults with cancer: Study design and protocol.

BACKGROUND: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. METHODS: Phase I design included qualitative interviews (n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool (n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15-24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. CONCLUSIONS: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610.

Impact of Hematopoietic Cell Transplantation on Cardiovascular Risk Factors and Insulin Sensitivity.

The use of hematopoietic cell transplantation (HCT) for treating malignant conditions in children has increased over the past five decades, leading to a growing population of long-term survivors.This population of childhood HCT survivors faces increased risks of adverse medical effects due to cancer treatments, including adverse cardiovascular disease (CVD) risk factors such as metabolic syndrome, insulin resistance. but the impact of exposure to HCT preparative conditioning regimen has not been clearly delineated. These risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance (IR), are significant contributors to premature cardiovascular disease and represent a leading cause of non-relapse deaths in childhood cancer and HCT survivors. This study aimed to assess the early development of CVD risk factors and their relationship to insulin resistance in a large population of pediatric and young adult HCT survivors of childhood hematologic malignancies. The study compared their cardiovascular risk profiles, insulin resistance (measured by euglycemic hyperinsulinemic clamp studies), and body composition (determined by dual X-ray absorptiometry - DXA) with a cohort of sibling controls. We enrolled 151 HCT recipients (26.36 ±0.90 years at study enrollment; time since HCT of 2.6-31.5 years) and 92 sibling controls to complete at cardiovascular risk assessment including insulin sensitivity by hyperinsulinemic euglycemic clamp, anthropometry, body composition by dual X-ray absorptiometry, blood pressure, and serum biomarkers. We used linear models to test for mean differences in all continuous outcomes between survivors and siblings, accounting for intra-family correlations with generalized estimating equations. Recipients of HCT were found to have lower insulin sensitivity and more likely to have adverse CVD risk factors in comparison to their healthy siblings. Significantly higher percent fat mass and visceral adipose tissue, and significantly lower lean body mass were noted in HCT recipients than sibling controls despite having a similar body mass index between the two groups. Total body irradiation in the conditioning regimen was one of the strongest factors associated with lower insulin sensitivity, dyslipidemia and abnormal body composition leading to sarcopenic obesity. This study reveals that pediatric and young adult HCT survivors are more insulin resistant and have a higher prevalence of adverse cardiovascular risk factors compared to sibling controls. The presence of cardiovascular risk factors at a relatively young age raises concerns about an escalating trajectory of cardiovascular disease in this population. Therefore, regular monitoring of HCT survivors for cardiometabolic risk factors and early intervention will be crucial for preventing cardiovascular-related complications in the future. The findings underscore the importance of survivorship care for pediatric and young adult HCT survivors, with a focus on managing cardiovascular risk factors and promoting a healthy lifestyle to mitigate long-term adverse effects. Early identification and targeted interventions can significantly improve the long-term health outcomes of this vulnerable population, reducing the burden of cardiovascular disease and related complications.

Socioeconomic Factors and Adherence to Health Care Recommendations in Adolescent and Young Adult Cancer Survivors.

Purpose: The majority of adolescent and young adult (AYA) cancer survivors do not receive recommended health care surveillance after therapy. We used cross-sectional survey data to evaluate the impact of income, education, marital status, and insurance on health care adherence among AYA survivors. Methods: Eligible survivors were 18-39 years at diagnosis with invasive malignancy, 1-5 years from therapy completion. Online surveys assessed sociodemographic factors and self-report of completion of recommended health care services. Diagnosis and treatment data were abstracted from medical records. Multivariable logistic regression calculated odds ratios (ORs) and 95% confidence intervals (CIs) for adherence in relation to socioeconomic status and support. Results: Of 344 participants, 36% were adherent to at least 80% of recommendations. Adherence varied by cancer type: 34% for breast cancer, 52% for leukemia/lymphoma, 23% for other tumors. Adherence rates were similar among White, Asian, and Hispanic/Latinx patients. Lower adherence was associated with lower education (OR: 0.43; 95% CI: 0.23-0.80 for <4-year college degree) and lower annual income (OR: 0.51; 95% CI: 0.28-0.95 for $41,000-$80,000; OR: 0.40; 95% CI: 0.19-0.86 for ≤$40,000). Adherence decreased with decreasing income levels among those who were 1 to less than 3 years after diagnosis (OR: 0.25; 95% CI: 0.07-0.93 for $81,000-$120,000; OR: 0.24; 95% CI: 0.07-0.84 for $41,000-$80,000; OR: 0.13; 95% CI: 0.03-0.60 for ≤$40,000). Conclusion: Risk of nonadherence to health care guidelines was associated with lower income and lower education among AYA cancer survivors. Identification of these risks and related barriers to adherence in AYA survivors will inform interventions designed to meet needs of these high-risk groups, particularly during the first years after diagnosis. Trial Registration: NCT02192333.

Barriers to medication adherence among adolescents and young adults with cancer.

BACKGROUND: Adherence promotion is a critical component of adolescent and young adult (AYA) cancer care, but predictors of nonadherence that could be targeted in intervention efforts remain largely unknown. The purpose of this multi-site longitudinal observational study was to examine the relationship between barriers and medication adherence among AYAs with cancer. PROCEDURE: Sixty-five AYAs (ages 15-24 years; mean age = 18.97 years, SD = 2.51; Mmean time since diagnosis = 1.42 years, SD = 1.95) with newly diagnosed or relapsed cancer completed self-report measures of barriers and adherence at quarterly study visits and used an electronic adherence monitoring device for 12 months. Longitudinal mixed effects models were used to examine our primary hypothesis that greater barriers are related to lower adherence over time. Descriptive statistics were used to explore our secondary aim of describing the frequency and patterns of barriers endorsed by AYAs with cancer. RESULTS: After controlling for covariates (time, medication type, race, ethnicity, diagnosis, time since diagnosis), a greater number of barriers was associated with lower electronically monitored (ß = -5.99, p = .005) and self-reported (ß = -1.92, p < .001) adherence. The specific barriers endorsed by AYAs differed across participants, and the majority of AYAs endorsed an entirely different pattern of barriers than any other AYA in the study. CONCLUSION: Barriers are associated with nonadherence and may be a promising target for intervention. Individual variability across barriers, however, suggests that tailoring may be necessary, and a promising next step is to explore personalized approaches to adherence promotion.

Pediatric Low-Grade Spindle Cell Neoplasm With A Novel AK5::ALK Fusion: A Case Report.

OBJECTIVES: Spindle cell neoplasms (SCN) share a single commonality of spindle-shaped cells on histopathology but are diverse in etiology. Expanding our collective knowledge of these neoplasms could further research in targeted therapies. We present a case of pediatric cutaneous SCN with a novel etiology, and the methods used to identify its origination. CASE PRESENTATION AND RESULTS: A 1.5-year-old child presented with a 7-month history of a rapidly enlarging, erythematous, non-painful scalp mass without ulceration or bleeding. The child underwent ultrasound and magnetic resonance imaging, revealing a 2.9 × 3 × 2 cm vascular mass without intracranial connections. The mass was successfully resected at surgery. Subsequent histopathologic and genetic testing indicated a SCN harboring a previously undescribed gene rearrangement between adenylate kinase 5 (AK5) and anaplastic lymphoma kinase (ALK). The patient received close clinical follow-up and at 6 months post-surgery had no recurrent disease. CONCLUSIONS: ALK rearrangements are common amongst many tumor types, but to our knowledge, AK5::ALK rearrangement has never been reported in SCN. Considering the rapid development of targeted clinical therapies, including those targeting ALK activity, this finding could be significant in the treatment of future patients with similar clinicopathologic and genetic presentation.

Chemotherapy roadmaps in pediatric oncology: A digital electronic medical record integrated solution.

BACKGROUND: Delivery of antineoplastic regimens in the pediatric setting is facilitated by a paper roadmap. Paper roadmaps are the key safety tool required for safe ordering. Electronic medical record systems offer technological solutions for ordering antineoplastic regimens, however, do not offer a solution that integrates paper roadmaps digitally. METHODS: A multidisciplinary project team implemented real-time clinician scanning of paper roadmaps into the electronic medical record. RESULTS: The rate of missing roadmaps decreased from an average of 1.6 to 0.8 per week. Pharmacists gained 3 h of productivity daily. Providers spend an average of 35-45 s and a total of seven clicks each time a roadmap is scanned. Overall, the clinical systems analyst spent less than 1 h of total build time. CONCLUSION: Implementing roadmap scanning decreased the rate of missing roadmaps, increased pharmacist productivity, and required a nominal amount of analyst and provider time. In addition, this solution allows for concurrent viewing of the roadmap files from any connected computer, facilitating an easier co-signature process for providers, pharmacists, and nurses. PRACTICE IMPLICATIONS: These results suggest that implementing real-time scanning of roadmaps can improve oncology care efficiency while maintaining the same safety rigor that paper roadmaps offer.

Feasibility and acceptability of a home-based resistance training intervention in adolescent and young adult hematopoietic cell transplant survivors.

BACKGROUND: Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness, and reduce risk of cardiovascular disease. PROCEDURE: Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose ≤1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics, and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were (a) 60% enrollment of approached patients, (b) 80% completion of weekly phone calls, and (c) 80% completion of the RT intervention and FU1 assessments. Acceptability was based on positive responses in qualitative interviews. RESULTS: Twenty of 31 (65%) eligible AYAs enrolled. Three participants failed to complete baseline measurements (2 = scheduling barriers, 1 = passive refusal) and four participants who completed baseline assessments did not receive the intervention (1 = medical reasons, 2 = no longer interested). Of those who completed baseline assessments, 13 received the intervention, completed 88.5% of coaching calls, and 11 (65%) completed FU1. LBM (kg) increased or remained unchanged in nine of nine participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4, 1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. CONCLUSIONS: A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Perioperative Cardiothoracic and Vascular Risk in Childhood Cancer and its Survivors.

CHILDREN with cancer and survivors of childhood cancer have an increased risk of cardiovascular disease, and this risk in the perioperative period must be understood. During diagnosis and treatment of pediatric cancer, multiple acute cardiovascular morbidities are possible, including anterior mediastinal mass, tamponade, hypertension, cardiomyopathy,and heart failure. Childhood cancer survivors reaching late childhood and adulthood experience substantially increased rates of cardiomyopathy, heart failure, valvular disease, pericardiac disease, ischemia, and arrhythmias. Despite considerable advances in the understanding and therapeutic options of pediatric malignancies, cardiac disease remains the most common treatment-related, noncancer cause of death in childhood cancer survivors. Increasingly, molecularly targeted agents, including small molecule inhibitors, are being incorporated into pediatric oncology. The acute and chronic risks associated with these newer therapeutic options in children are not yet well-described, which poses challenges for clinicians caring for these patients. In the present review, the unique risks factors, prevention strategies, and treatment of cardiovascular toxicities of the child with cancer and the childhood cancer survivor are examined, with an emphasis on the perioperative period.

Feasibility of a behavioral intervention using mobile health applications to reduce cardiovascular risk factors in cancer survivors: a pilot randomized controlled trial.

PURPOSE: Determine the feasibility of a remotely delivered mobile health (mHealth)-supported intervention to improve diet and physical activity in hematologic malignancy survivors. METHODS: Pilot randomized controlled trial of a 16-week intervention for improving diet and physical activity: individualized goal-setting (daily steps, sodium, saturated fat, added sugar intake) per feedback from mHealth trackers (Fitbit for activity; Healthwatch360 for diet), supplemented by a Facebook peer support group. Controls accessed the trackers without goal-setting or peer support. Everyone received standardized survivorship counseling with tailored advice from a clinician. Actigraphy and food frequency questionnaires assessed activity and diet at baseline and follow-up. RESULTS: Forty-one participants (51.2% male; median age 45.1 years; 7.0 years from treatment) were randomized (24 intervention; 17 control). Fitbit and Healthwatch360 use were more common among intervention versus control participants (75.0% versus 70.6% and 50.0% versus 17.7% of eligible days, respectively). Most intervention participants (66.7%) engaged with Facebook; overall, 91.7% interacted with the study's mHealth applications. While no comparisons in activity or dietary outcomes between intervention versus control group met statistical significance, the intervention was associated with greater reductions in the targeted dietary factors and improvements in Healthy Eating Index-2015 score, moderate-vigorous physical activity time, and daily steps. Participant retention at 6 months was 90.2%. CONCLUSIONS: An intervention for cardiovascular risk reduction based on individualized goal-setting enhanced by mHealth and social media peer support was feasible and acceptable among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Effective and easily disseminated strategies that improve diet and physical activity in this population are needed. TRIAL REGISTRATION: Registered in ClinicalTrials.gov (NCT03574012) on June 29, 2018.

Sexual Activity and Substance Use Among Adolescents and Young Adults Receiving Cancer Treatment: A Report from the PRISM Randomized Controlled Trial.

Purpose: Despite health implications, sexual activity and substance use among adolescents and young adults (AYAs) receiving cancer treatment are understudied. Methods: AYAs 12-25 years of age participated in a randomized controlled trial testing the efficacy of a resilience intervention. They were fluent in English and either diagnosed with new cancer (NC) or advanced cancer (AC). At baseline and 6 months, participants self-reported sexual activity and substance use. We describe the percentage of AYAs who endorsed each behavior and a count of total behaviors endorsed by each respondent. We describe frequencies by sex/gender (male/female), age (<18/≥18), and disease status (AC/NC). Results: Participants (N = 92) were majority white/Caucasian (57%), 12-17 years old (73%), and diagnosed with leukemia/lymphoma (62%); 32% had AC. Responses were not associated with the intervention; hence, we summarized data from the whole cohort. At both time points, median behavior endorsed was 2. At baseline and follow-up, 87% and 81% endorsed at least 1 behavior: 13% and 15% were sexually active, 75% and 73% of whom used birth control inconsistently; and 22% and 22% reported drinking alcohol, 31% and 27% using prescription opioids/sedatives, 19% and 22% using other drugs, and 9% and 7% using tobacco. Young adults engaged in most behaviors more frequently than adolescents (e.g., 48% vs. 12% alcohol at baseline); males engaged in sexual activity more frequently than females (e.g., 20% vs. 5% sexually active at baseline); and AYAs with NC engaged in most behaviors more frequently than those with AC (18% vs. 0% sexually active at baseline). Conclusion: AYAs engage in sexual activity and substance use during cancer treatment.

Lasting effects of cancer and its treatment on employment and finances in adolescent and young adult cancer survivors.

BACKGROUND: The impact of cancer and its treatment on employment and financial burden in adolescents/young adults (AYAs) is not fully known. METHODS: Eligibility for this cross-sectional study of AYA cancer survivors included the diagnosis of a malignancy between ages 18 and 39 years and survey completion within 1 to 5 years from diagnosis and ≥1 year after therapy completion. Participants were selected randomly from the tumor registries of 7 participating sites and completed an online patient-reported outcomes survey to assess employment and financial concerns. Treatment data were abstracted from medical records. Data were analyzed across diagnoses and by tumor site using logistic regression and Wald-based 95% confidence intervals adjusting for age (categorized), sex, insurance status, education (categorized), and treatment exposures. RESULTS: Participants included 872 survivors (breast cancer, n = 241; thyroid cancer, n = 126; leukemia/lymphoma, n = 163; other malignancies, n = 342). Exposure to chemotherapy in breast cancer survivors was associated with an increase in self-reported mental impairment in work tasks (odds ratio [OR], 2.66) and taking unpaid time off (OR, 2.62); survivors of "other" malignancies reported an increase in mental impairment of work tasks (OR, 3.67) and borrowing >$10,000 (OR, 3.43). Radiation exposure was associated with an increase of mental impairment in work tasks (OR, 2.05) in breast cancer survivors, taking extended paid time off work in thyroid cancer survivors (OR, 5.05), and physical impairment in work tasks in survivors of "other" malignancies (OR, 3.11). Finally, in survivors of "other" malignancies, having undergone surgery was associated with an increase in physical (OR, 3.11) and mental impairment (OR, 2.31) of work tasks. CONCLUSIONS: Cancer treatment has a significant impact on AYA survivors' physical and mental work capacity and time off from work.

Association of Pre-pregnancy BMI and Postpartum Weight Retention Before Second Pregnancy, Washington State, 2003-2013.

Background Maternal overweight and obesity is one of the most common high-risk obstetric conditions associated with adverse birth outcomes. Smaller studies have suggested that pre-pregnancy body mass index (BMI) is associated with postpartum weight retention. Objective The primary objective of this study was to examine the association between pre-pregnancy BMI status and maternal weight retention. Study design We conducted a population-based retrospective cohort study using Washington State birth certificate data from 2003-2013. We included women who had two sequential births during this time period, with the second birth occurring within 18-36 months of the first singleton delivery date. BMI before a women's first pregnancy ("pre-pregnancy BMI") was categorized as normal (18.5-24.9 kg/m2) and overweight/obese (25-40 kg/m2). Women were classified as having returned to first pre-pregnancy BMI if their BMI before their second pregnancy was no more than 1 kg/m2 more compared to their BMI before their first pregnancy. Analyses were stratified by gestational weight gain during the first pregnancy (below, met, exceeded recommended gestational weight gain). Results A total of 49,132 mothers were included in the study. Among women who met their recommended gestational weight gain, compared to mothers with a normal BMI, obese/overweight mothers were less likely to return to their pre-pregnancy BMI (76.5 vs 72.3%; RRObese/Overweight = 0.88; 95% CI: 0.85-0.92). A similar pattern was observed among women who exceeded their recommended gestational weight gain (62.6 vs 53.2%; RRObese/Overweight = 0.79, 95% CI: 0.78-0.80). Conclusion Pre-pregnancy BMI in the overweight/obese range is associated with a decreased likelihood of returning to pre-pregnancy BMI. Further research to support women during and after their pregnancy to promote behavior changes that prevent excessive weight gain during pregnancy and weight retention after birth is needed.

Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors.

Adult survivors of acute leukemia in childhood have a higher-than-expected frequency of obesity and are at increased risk for metabolic syndrome and early mortality from cardiovascular disease (CVD). Adipose tissue has been recognized as an endocrine and paracrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. In this study, we examined inflammatory factors (IL-6 and TNF-α) and adipokines (adiponectin, leptin), in addition to body composition and adiposity, in cancer survivors who underwent hematopoietic cell transplantation (HCT) during childhood compared with sibling controls. Over 2-year survivors of HCT for hematologic malignancies during childhood were recruited from 2 institutions along with a control population of siblings. Participants underwent evaluation for body composition, anthropometric measurements, and assessment of CVD risk factors and adipokines. Cases were stratified by radiation exposure in the preparative regimen (total body irradiation [TBI] + central nervous system [CNS] irradiation, TBI only, chemotherapy only) and adjusted least squares means were estimated for each adipokine and adjusted by age, sex, race, Tanner stage, and percent fat mass (PFM) percentiles (0-24, 25-74, 75+). A total of 151 HCT survivors and 92 siblings underwent evaluation. Significant differences in mean adipokine levels were detected between survivors and siblings; leptin was significantly higher and adiponectin significantly lower in HCT survivors who received TBI with or without CNS irradiation compared with siblings. IL-6 was significantly higher in all groups of HCT survivors compared with siblings. Body mass index (BMI) was similar in survivors and controls, although PFM was significantly higher in all groups of HCT survivors and lean body mass (LBM) was lower in survivors who received TBI with or without CNS radiation compared with siblings. HCT survivors showed an unfavorable profile of inflammation, adipokines, and adiposity, despite similar BMI as controls. Higher PFM and lower LBM may contribute to these findings. TBI exposure is correlated with greater severity of these observations. Increasing LBM may represent a tangible target for mitigating the high cardiometabolic risks of HCT survivors.

Progression of Hip Dysplasia in Mucopolysaccharidosis Type I Hurler After Successful Hematopoietic Stem Cell Transplantation.

BACKGROUND: Dysostosis multiplex contributes substantially to morbidity in patients with Hurler syndrome (mucopolysaccharidosis type I Hurler phenotype [MPS I-H]), even after successful hematopoietic stem cell transplantation (HSCT). One of the hallmarks of dysostosis multiplex in MPS I-H is hip dysplasia, which often requires surgical intervention. We sought to describe in detail the course of hip dysplasia in this group of patients, as assessed by radiographic analysis, and to identify potential outcome predictors. METHODS: Longitudinal data were obtained from digitally scored pelvic radiographs of patients with MPS I-H using OrthoGon software for parameters including, but not limited to, the acetabular index, migration percentage, Smith ratio, and neck-shaft angle. Scoring was performed independently by two blinded observers. Additional information on genotype, enzyme replacement therapy pre-HSCT, donor chimerism, and enzyme activity post-HSCT were obtained. General trends and potential correlations were calculated with mixed-model statistics. RESULTS: Fifty-two patients (192 radiographs) were included in this analysis. Intraobserver and interobserver variation analysis showed an intraclass correlation coefficient ranging from 0.78 to 1.00. Among the twenty-one patients with follow-up beyond the age of five years, the acetabular index was in the range of severe hip dysplasia in up to 86% of the patients. Severe coxa valga was seen in 91% of the patients. Lateral and superior femoral displacement were highly prevalent, with the migration percentage outside the reference range in up to 96% of the patients. Finally, anterior pelvic tilt increased with age (p = 0.001). No correlations were identified between clinical parameters and radiographic findings. CONCLUSIONS: Our study shows that progressive acetabular dysplasia as well as coxa valga and hip displacement are highly prevalent and progressive over time in patients with MPS I-H, despite successful HSCT. These data may provide essential natural history determinations for the assessment of efficacy of new therapeutic strategies aimed at improving skeletal outcomes in patients with MPS I-H.

Ofatumumab for refractory opsoclonus-myoclonus syndrome following treatment of neuroblastoma.

Opsoclonus-myoclonus syndrome (OMS) may be associated with ANNA-1 (anti-Hu) autoantibodies. The standard treatment with IVIG, steroids, and anti-CD20 monoclonal antibody may fail, and optimal therapy is unknown. A patient developed OMS with high-titer ANNA-1 following recovery from neuroblastoma. She failed standard therapy and had only transient response to rituximab. Treatment with the humanized anti-CD20 monoclonal antibody ofatumumab combined with methotrexate resulted in transient neurologic improvement and decrease of ANNA-1. This suggests that ofatumumab combined with methotrexate should further be considered OMS patients, particularly in refractory disease.