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Purpose Patients 16 to 21 years of age with acute lymphoblastic leukemia (ALL) have an inferior outcome compared with younger children, leading some medical oncologists to advocate allogeneic stem-cell transplantation in first remission for these patients. We examined outcome for young adults with ALL enrolled onto the Children's Cancer Group (CCG) 1961 study between 1996 and 2002. Patients and Methods CCG 1961 entered patients with ALL 1 to 21 years of age with initial WBC count ≥ 50,000/μL and/or age ≥ 10 years. Randomly assigned therapies evaluated the impact of postinduction treatment intensification on outcome. We examined outcome and prognostic factors for 262 young adults with ALL. Results Five-year event-free and overall survival rates for young adult patients are 71.5% (SE, 3.6%) and 77.5% (SE, 3.3%), respectively. Rapid responder patients (< 25% bone marrow blasts on day 7) randomly assigned to augmented therapy had 5-year event-free survival of 81.8% (SE, 7%), as compared with 66.8% (SE, 6.7%) for patients receiving standard therapy (P = .07). One versus two interim maintenance and delayed intensification courses had no significant impact on event-free survival. WBC count more than 50,000/μL was an adverse prognostic factor. Conclusion Young adult patients with ALL showing a rapid response to induction chemotherapy benefit from early intensive postinduction therapy but do not benefit from a second interim maintenance and delayed intensification phase. Given the excellent outcome with this chemotherapy, there seems to be no role for the routine use of allogeneic stem-cell transplantation in first remission for young adults with ALL.

To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV).Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS.A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV-non-NF1 group (P .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV-treated children without NF1. NF1 patients and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non-NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV-NF1 group) at a median of 7.8 years (range, 7.3-9.4 years) after enrollment, but there were none in the non-NF1 group.Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928-36. © 2016 American Cancer Society.

Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure are not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21 years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy (“Induction”). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p

Objectives To discuss recent and current initiatives to increase enrollment of adolescents and young adult (AYA) cancer patients onto National Cancer Institute-funded clinical trials to improve outcomes. Data Sources Peer-reviewed publications, websites of professional organizations. Conclusion Despite many challenges facing AYAs, recent studies illustrate that AYA-focused cancer clinical trials can be successfully developed and conducted. Development of the National Cancer Institute National Clinical Trials Network and related AYA-focused initiatives create new opportunities to expand clinical trials that serve AYAs. Implications for Nursing Practice Nurses can influence AYA outcomes by leveraging their roles as educators and collaborators to increase participation in cancer clinical trials.

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled “Next Steps in Adolescent and Young Adult Oncology” on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

Survivors of acute lymphoblastic leukemia have increased risk for long-term cardiovascular complications. Early identification of cardiovascular risk factors (CVRF) may allow for effective interventions. In this retrospective cohort study of 194 patients at Children's Hospital Los Angeles, we investigated CVRF screening practices in an established childhood cancer survivorship program relative to both the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines and American Academy of Pediatrics (AAP) recommendations. CVRF screening practices met COG but not the more stringent AAP recommendations, particularly in areas of dyslipidemia and diabetes screening. Implications of our findings are discussed.

Over the past 30 years, adolescents and young adults (AYA, 15–39 years of age) with cancer have shown significantly less improvement in survival than younger and older patients. Because evidence suggests this may be related to their low participation in cancer clinical trials, increasing accrual to these trials has become a priority for closing this “AYA gap.” This paper reviews data documenting low AYA enrollment, presents a conceptual framework for research and intervention (Clinical Trials Pathway to Enrollment) and summarizes recent developments in the United States National Cancer Institute-sponsored clinical trials enterprise that are expected to improve AYA enrollment, including the National Clinical Trials Network (NCTN) and expanded scientific collaboration between the Children’s Oncology Group and adult NCTN groups. While time will be required for the effects of these changes to be fully realized, they offer a mechanism for facilitating the breadth of clinical/translational research needed for advancing AYA oncology and measuring its impact.

Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities.We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991.Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5-5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males.This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice.

Health-promoting behaviors are recommended to childhood cancer survivors (CCS) to reduce late effects resulting from cancer treatment. Understanding factors associated with substance use is needed, especially among Hispanic CCS who are underrepresented in previous studies. The objective of this study is to examine substance use behaviors of recently treated Hispanic and non-Hispanic CCS.One hundred ninety-three Los Angeles County CCS who were diagnosed between 2000 and 2007 (54% Hispanic; mean age 19.9 years, SD = 2.8; mean age at diagnosis = 12.1, SD = 3.0; mean years since diagnosis = 7.8, SD = 2.0) provided self-reported information on substance use, demographics, clinical factors, religiosity, and depressive symptoms. Risk and protective factors for substance use were examined using multivariable logistic regression.Prevalence of 30-day substance use was 11%, 25%, and 14% for tobacco, alcohol, and marijuana, respectively. In controlled regression models, age was positively associated with tobacco use, binge drinking, and polysubstance use (use of at least two of the three substances). Male gender, higher depressive symptoms, and higher socioeconomic status were associated with greater marijuana use. In addition, religiosity was negatively associated with the use of all substances.The prevalence rates for substance use in this ethnically diverse representative sample of CCS are lower than those observed in the general population. Older CCS were at higher risk of substance use, and depression was associated with greater marijuana use. No differences by ethnicity were observed. Interventions for substance use prevention/cessation among CCS may be most effective if implemented before the age of 21 years and address mental health as part of survivorship care. Copyright © 2015 John WileySons, Ltd.

For children, adolescents, and their families, the cancer experience is characterized by a series of transitions that begins at diagnosis and, for most patients, ends with entry into long-term survivorship care. Each of these transitions has specific implications for medical care provided during those phases. In pediatric and adolescent oncology, these cancer-related transitions do not occur in isolation but in the context of normal physical, emotional, and social development. Therefore, the successive phases of developmental maturation that begin in infancy and continue through older adolescence not only influence each patient’s response to cancer-related transitions but also require support during the cancer experience in order for healthy adulthood to be achieved.

Major transitions that occur during the management of childhood cancer take place against a backdrop of each patient’s normal physical, emotional, and social developmental tasks. This chapter provides an overview of these transitions, emphasizing those which occur following completion of treatment, during the long-term follow-up phase. Because many survivors are at a lifelong increased risk for developing clinically significant complications of their cancer therapy, systematic surveillance for late effects and other survivorship support is recommended across the lifespan. This requires formal transition of survivorship care from pediatric to adult-focused providers using one of several available models. Addressing formidable barriers that may be encountered is essential for achieving successful health care transition for the childhood cancer survivor.

The adolescent at the end of life poses a unique combination of challenges resulting from the collision of failing health with a developmental trajectory meant to lead to attainment of personal independence. Because virtually all spheres of the dying adolescent's life are affected, optimal palliative care for these young persons requires a multidisciplinary team whose members have a good understanding of their complementary roles and a shared commitment to providing well-coordinated care. Members of the team include the physician (to initiate and coordinate palliative care management); the nurse (to work collaboratively with the physician and adolescent, especially through effective patient advocacy); the psychologist (to assess and manage the patient's neurocognitive and emotional status); the social worker (to assess and optimize support networks); the chaplain (to support the adolescent's search for spiritual meaning); and the child life specialist (to facilitate effective communication in preparing for death). A crucial area for dying adolescents is medical decision making, where the full range of combined support is needed. By helping the young person continue to develop personal autonomy, the multidisciplinary team will enable even the dying adolescent to experience dignity and personal fulfillment.

With nearly 80% of childhood cancer patients achieving cure, there are more adult survivors living now than at any other time in history. Because they are at risk for developing complications of treatment years later, it is recommended that survivors undergo systematic, regular monitoring into young adulthood and beyond. Occasionally, older adolescents and young adults are diagnosed with a relapsed, secondary or primary malignancy that requires urgent care. How best to manage each of these situations is a major challenge. A review of literature and clinical experience was performed. The medical, developmental, and psychosocial characteristics of older adolescents and young adults argue for a planned transition of care from a pediatric to more appropriate adult setting at that age. The 'health-oriented transition' involves the relatively healthy survivor, where an adult-oriented provider must be identified and supplied with a comprehensive treatment history, problem list, and monitoring plan. Continuity of medical insurance coverage must be preserved. The 2 basic models for this type of transition are either institution- or community-based. Each has relative advantages and disadvantages. In both, education and empowerment of the survivor are fundamental. The 'crisis-oriented transition' involves the older adolescent or young adult who is diagnosed in the pediatric setting with relapsed, secondary or primary cancer and is rapidly moved into the adult setting to begin treatment. With minimal time for preparation, this transition requires collaborative efforts by the pediatric and adult oncology teams. Having the capability to address both types of transition should be a central goal of any pediatric and adolescent oncology program.

With improvements in therapy for childhood cancer, the expectation that most childhood cancer patients will survive and enter adulthood is a reality. There is clear evidence that survivors are at risk for adverse health-related long-term sequelae associated with their cancer and its treatment, requiring appropriate health care resources. What is less clear is how this health care should optimally be delivered. We review the functional and operational needs for long-term follow-up for childhood cancer survivors and present alternatives for models of care. Programs for childhood cancer survivors should provide mechanisms for monitoring and management of late effects, as well as support and advocacy for addressing psychosocial issues, health education, and assistance with financial concerns. Access to research is an important component as clinical care and research are integrally related. A multidisciplinary model that provides continuity of care throughout the disease course is optimal, providing transitions from acute anti-neoplastic therapy to follow-up and primary care, as well as from pediatric care to adult-oriented care. There is no single best model of care for all childhood cancer survivors. In evaluating different models, considerations include available resources as well as the particular cancer population being served. Not all survivors require the same level of services and the service level requirement for individual patients may change with time. As outcome research progresses for childhood cancer survivors, methodological issues of optimal health care delivery for this population deserve to be the subject of such research.

To the editor: Gupta et al[1][1] concluded that young adult patients with acute lymphoblastic leukemia (ALL) aged 15 to 35 years should be treated in first remission with allogeneic transplant. They based their judgment on a meta-analysis of 13 studies, each of which had a control regimen used

Hyper-IgM (HIM) syndrome encompasses a family of congenital immunodeficiency states characterized by frequent infections and markedly low serum levels of IgG, IgA, and IgE but normal or elevated levels of IgM. Many patients have neutropenia. The major defect shared by all forms of HIM syndrome is a failure of immunoglobulin isotype-switching. Recently, a flow cytometric assay was described in the immunology literature for diagnosis of patients with inherited X-linked (X-HIM) syndrome. Using this assay, activated CD4 peripheral blood T lymphocytes from two patients suspected of having HIM syndrome, and from their mothers, were subjected to immunofluorescent flow cytometric analysis for the expression of CD40 ligand (CD154 antigen). Test results established the diagnosis of X-HIM syndrome that was inherited in one patient and spontaneous in the other. The authors' experience illustrates that the flow cytometric assay used and described in detail here can facilitate an accurate and timely diagnosis of X-HIM syndrome. Because the assay can be carried out in most clinical flow cytometry facilities, it lends itself to use by pediatric hematologists in the standard evaluation of patients whose differential diagnosis includes that disorder. The authors hope this report will raise awareness of the value of this procedure.

Introduction: For many forms of cancers, survival improvement in the AYA population has lagged behind that of younger patients. One contributing factor could be differences in drug metabolism and tolerance of cancer treatment. Although previous studies have documented greater vincristine-related neurotoxicity (VRNT) in AYA vs. younger patients, comparative vincristine PK studies have yielded mixed results with no clear difference in PK related to age. One limitation of these studies is that age, rather than a more physiological assessment of developmental maturity, was used for the comparison. The primary aim of this study was to determine whether developmental differences in vincristine PK related to Tanner Stage could be detected in a sample of children and AYAs undergoing treatment for ALL. Our hypothesis was that vincristine PK would be related to Tanner Stage. Methods: From September 2014-March 2015, a purposeful sample of 30 patients with a diagnosis of ALL treated at Children9s Hospital of Los Angeles were recruited to this IRB-approved study either prior to starting Induction phase or during Maintenance phase. Tanner Stage was classified as ≤2 or ≥4, excluding Tanner Stage 3. Vincristine blood levels were obtained around the first dose during Induction or any single monthly dose during Maintenance at pre-specified time points: 0 min, 10 min, 30 min, 1 hour, 12 hour (Induction only), and 24 hours. For all patients, the vincristine dose was 1.5 mg/m 2 (max 2 mg). Vincristine levels were determined by high performance liquid chromatography. Mean vincristine clearance was compared using the independent T-test. Univariate and multivariate linear regression analysis via backward selection was performed using Tanner Stage, age, sex, BMI, fluconazole exposure, and treatment phase as predictors. P-values were two-sided with significance set at Results: The age range was 1-24 yrs ( 2 , respectively (p=0.71). As summarized in Tables 1 and 2, in both univariate and multivariate analyses no predictors, including Tanner Stage, were associated with vincristine clearance. Conclusions: In this pilot study, we were unable to detect an association between vincristine clearance and Tanner Stage. These data suggest that even when using a measure more reflective of physiological maturity than age, substantial developmental differences in vincristine clearance appear to be lacking. This calls into question the potential explanation of altered clearance for the increased VRNT observed in AYAs, and suggests that future investigations should be directed toward potential developmental differences in vincristine pharmacodynamics. Our data may have implications for understanding other differences in chemotherapy toxicity observed in AYAs. Disclosures No relevant conflicts of interest to declare.

Background/Purpose: The optimal management for typhlitis in pediatric oncology patients has not always been clear from the medical literature. Trends have varied between operative and nonoperative approaches. The aim of this study was to review the successful nonoperative management of these patients at our institution over the last decade to further clarify management guidelines for this difficult problem. Methods: Medical records of pediatric hematology and oncology patients up to 21 years of age with typhlitis diagnosed at the DeVos Children's Hospital from 1990 to 2000 were reviewed. Results: Twelve patients were included. Ten patients (83%) with computed tomography (CT) scans suggestive of the diagnosis were treated successfully nonoperatively. Management usually included bowel rest, antibiotics, and supplemental parenteral nutrition. Two patients (17%) in whom CT scans were not obtained underwent surgery for presumed appendicitis and pneumoperitoneum, respectively. Typhlitis was found incidentally. In the latter patient, the pneumoperitoneum resulted from a perforated jejunum caused by graft-versus-host disease. This patient died of septic complications and was the only mortality in the series (8%). Conclusions: Pediatric cancer patients with typhlitis can be treated carefully nonoperatively with bowel rest, antibiotics, and supplemental nutrition. Usual indications for surgery (ie, perforation, clinical deterioration) still should be used. The early use of CT scanning helps to facilitate the diagnosis and may provide the ability to differentiate typhlitis from other abdominal diseases for which surgery would be indicated. J Pediatr Surg 37:1151-1155. Copyright 2002, Elsevier Science (USA). All rights reserved.

Background This study sought to characterize cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Procedure In this cross-sectional cohort study, Latino survivors of ALL (n = 57) and LL (n = 5) aged 6–16 years were pooled and evaluated using validated measures of cognitive, academic, and behavioral function and English language proficiency. Performance was compared with norms using single-sample t-tests. Results In this cohort (n = 62, 50% male), mean ages at diagnosis and testing were 4.5 and 10.8 years, respectively; mean time off treatment was 44.7 months. All participants spoke English and over half (57%) identified Spanish as the primary language in the home. Forty-two families (68%) placed in the two lowest Hollingshead socioeconomic status categories. Participants were below average for working memory (P

e21043 Background: Melanoma is the third most common cancer among adolescents and young adults (AYAs; aged 15-39). Disease characteristics have not been well-described in this age group, particularly among diverse populations. We describe clinical features of AYAs diagnosed with melanoma at a large public hospital serving an ethnically diverse population. Methods: We reviewed medical chart data from patients diagnosed with melanoma between 2001-2016 at Los Angeles County + USC Medical Center. We describe clinical characteristics of AYA patients and compare to non-AYAs (aged ≥40) using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. Results: Of the 273 melanoma patients identified, 47 (17.3%) were AYAs (mean age 32.3; SD±4.45; lower age range 18). The majority of patients were Hispanic (AYA, 53.2%; non-AYA, 51.1%), followed by non-Hispanic whites (AYA, 38.3%; non-AYA, 38.7%). A greater proportion of AYA patients were female (59.6%) compared to non-AYAs (38.2%) (p < 0.01). No AYA patients reported prior skin cancer compared to 19.9% of non-AYAs; 8.5% of AYAs reported family history of melanoma compared to 6.3% of non-AYAs. For all patients, superficial spreading melanoma was the most common histological subtype (AYA, 21.3%; non-AYA, 20.9%). Nodular melanoma was the second most common subtype in AYAs (17.02%) in contrast to acral lentiginous melanoma among non-AYAs (20.9%). Median Breslow depth was 3.0 mm for AYAs and 2.55 mm among non-AYAs. A slightly higher percentage of AYAs were diagnosed with regional disease (31.9%) than non-AYAs (24.4%), and a greater proportion of non-AYAs presented with distant metastases (AYA, 6.4%; non-AYA, 18.7%). The most common site of diagnosis were the extremities for all patients (AYA, 45.0%; non-AYA, 29.3%). Conclusions: We found similar clinical characteristics between AYA and non-AYA melanoma patients. However, we found a statistically significant difference for gender. The increased incidence of melanoma in female AYAs may be driven by biological factors such as sex hormones or genotype, or tanning behaviors. Further research is warranted to identify predictive and prognostic factors of melanoma among diverse AYAs, particularly females.

Background The adverse effects of irradiation on endocrine function among patients with pediatric brain tumor are well documented. Intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) without central nervous system (CNS) irradiation has demonstrated efficacy in a proportion of very young children with some malignant CNS tumors. This study assessed the long-term endocrine function of young children following chemotherapy-only treatment regimens. Procedures A retrospective chart review was performed on 99 patients under 6 years of age with malignant brain tumors newly diagnosed between May 1991 and October 2010 treated with irradiation-avoiding strategies. Thirty patients survived post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0–22.25 years). The patient cohort included 18 males and 12 females (mean age at AuHCR of 2.5 years, range 0.8–5.1 years). Results All 30 surviving patients had documented normal age-related thyroid function, insulin-like growth factor binding protein 3 (IGF-BP3), prolactin, testosterone, and estradiol levels. Insulin-like growth factor 1 age-related levels were abnormal in one child with normal height. Ninety-seven percent of patients had normal cortisol levels, while follicle-stimulating hormone and LH levels among females were normal in 83% and 92%, respectively, and in 100% of males. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% of patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. Conclusions These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation.

197 Background: Because childhood cancer survivors (CCS) report a high number of unmet cancer-related information needs, knowing where CCS access information may provide insights into appropriate delivery systems to address information deficits. Active seeking of health information among CCS is associated with positive health behaviors, including adherence to follow-up care. This study examined patterns of cancer-related health information seeking as an indicator of health care engagement. Methods: Participants (N = 193) were young adult CCS diagnosed with any cancer type in Los Angeles County, 54% Hispanic, with a mean age of 19.87, and at least two years from treatment. CCS were asked where they accessed health information related to their cancer with 8 response options which were categorized into four information domains: hospital resources, social media, other survivors, and family members. Multivariable logistic regression was used to assess correlates of each information domain, including sociodemographic information, post-traumatic growth, and health care engagement, controlling for age, ethnicity, sex, education, and health insurance status. Results: Hospital resources were the most frequently endorsed information domain (65.3%), and Hispanic CCS (vs. non-Hispanic) were more likely to access this source. Online sources were more likely accessed by female CCS. Seeking information from other cancer survivors was associated with follow-up care and post-traumatic growth after cancer. Hispanic CCS were less likely to seek information from other survivors and their family than non-Hispanics. Conclusions: While CCS obtain information from a variety of sources, hospital resources were the most commonly accessed, particularly for Hispanics. Information sharing between survivors may promote positive health care engagement; however, Hispanics may be less likely to pursue this resource. Future work should address barriers Hispanic CCS face in information sharing with other cancer survivors. [Table: see text]

Purpose: To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. Experimental Design: Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m2 anthracyclines [high risk (HR): n = 100] were compared with those treated with Results: Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: −0.62, LR: −0.03, HC: −0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm2, LR: 56.6 g/cm2, HC: 54.2 g/cm2; P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76–0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. Conclusion: Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction. Clin Cancer Res; 20(24); 6314–23. ©2014 AACR.

Follow-up care is critical for childhood cancer survivors (CCS), who are at high risk for comorbidities and late effects of cancer treatments. Understanding the factors associated with maintaining follow-up care is needed, especially for Hispanic CCS, who have been under-represented in previous studies.Risk factors and protective factors for receiving cancer-related follow-up care were examined among 193 Los Angeles County CCS diagnosed between 2000 and 2007 (54% Hispanic; mean ± standard deviation age, 19.9 ± 2.8 years; age at diagnosis, 12.1 ± 3.0 years; time since diagnosis, 7.8 ± 2.0 years). Self-report surveys were used to assess follow-up care, insurance status, demographics, clinical factors, and psychosocial risk (eg, depression) and protective (eg, self-efficacy [SE]) factors. Multivariable logistic regression was used to identify factors associated with the previous receipt of cancer-related follow-up care (in prior 2 years) and the intent to seek future cancer-related follow-up care.Seventy-three percent of CCS reported a cancer follow-up visit in the previous 2 years, which was positively associated (P .05) with having health insurance, white ethnicity (vs Hispanic), younger age, and greater treatment intensity. Sixty-nine percent reported an intent to receive follow-up care in the next 2 years, which was positively associated (P.05) with having health insurance and greater SE.Hispanics and older CCS were more likely to lack previous follow-up care. Because health insurance was strongly associated with both previous follow-up care and the intent to seek care, the current results indicate that recent changes in health coverage may improve follow-up among CCS. Interventions targeting improved SE may help increase intent to receive follow-up care for this population.

Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6–37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m2 (25–642 mg/m2). Thirty-five (23%) participants had cardiac dysfunction—defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109–14. ©2014 AACR.

Purpose Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity. Patients and Methods In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses. Results Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT. Conclusion Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.

Background Accrual to Cancer Control and Supportive Care (CCL) studies can be challenging. Our objective was to identify facilitators and perceived barriers to successful Children’s Oncology Group (COG) CCL accrual from the clinical research associate (CRA) perspective. Methods A survey was developed that focused on the following features from the institutional perspective: (1) Components of successful accrual; (2) Barriers to accrual; (3) Institutional changes that could enhance accrual; and (4) How COG could facilitate accrual. The survey was distributed to the lead CRA at each COG site with at least 2 CCL accruals within the previous year. The written responses were classified into themes and sub-themes. Results 57 sites in the United States (n = 52) and Canada (n = 5) were contacted; 34 (60%) responded. The four major themes were: (1) Staff presence and dynamics; (2) Logistics including adequate numbers of eligible patients; (3) Interests and priorities; and (4) Resources. Suggestions for improvement began at the study design/conception stage, and included ongoing training/support and increased reimbursement or credit for successful CCL enrollment. Conclusions The comments resulted in suggestions to facilitate CCL trials in the future. Soliciting input from key team members in the clinical trials process is important to maximizing accrual rates.

Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols.Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained.The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes.In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

Purpose To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V 22 (volume of lung exposed to a radiation dose ≥22 Gy) and V 30 (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V dose (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome ( P =.01). Conclusions Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.

OBJECTIVE: Juvenile xanthogranuloma (JXG) with systemic (extracutaneous) involvement is a rare histiocytic disorder in which significant morbidity and occasional deaths may occur. The objective of this study was to characterize the spectrum of anatomic involvement, associated clinical problems, and management considerations in children with systemic JXG. STUDY DESIGN: Two current cases and literature reports of 34 children with various forms of systemic JXG were analyzed with respect to age, clinical presentation, site(s) of involvement, therapy, and outcome. RESULTS: The median age of the 36 patients was 0.3 years (range, birth to 12 years). Symptoms were usually referable to bulky or infiltrative disease. Twenty patients had disease in two or more sites. Cutaneous lesions were present in fewer than half the patients. The most frequent extracutaneous sites of disease were the subcutaneous soft tissue (12); central nervous system (8); liver/spleen (8); lung (6); eye/orbit, oropharynx, and muscle (4 each); with three or fewer instances of disease in each of several other sites. Most patients were treated with excision or had spontaneous regression (some with organ involvement). However, 12 patients received treatment that included radiation or systemic chemotherapy. Survivors, some with long-term disabilities, included young children who had received radiation therapy to the brain, eye, skin, or heart. Two patients died of disease. CONCLUSIONS: Systemic JXG may involve varying numbers and combinations of extracutaneous sites. The extent of disease should be determined in patients with JXG who are suspected to have systemic involvement. In contrast to the cutaneous form, systemic JXG may be associated with significant complications requiring aggressive medical care. When feasible, surgical excision of lesions may be curative. Optimal treatment for symptomatic, unresectable disease is currently undefined but should be selected to minimize toxic effects in these children who are typically younger than 1 year old at presentation. (J P EDIATR 1996;129:227-37)

OBJECTIVE: To catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB). METHODS: Data have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible. RESULTS: In 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations. CONCLUSIONS: The occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases. (J P EDIATR 1996;128:220-4)

LG-65. CLINICOPATHOLOGICAL FEATURES AND OUTCOME IN ADOLESCENTS/YOUNG ADULTS (AYA) WITH LOW GRADE GLIOMA (LGG) COMPARED WITH CHILDREN: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP Ashley Margol1,3, Caihong Xia4, Richard Sposto2,3, David Freyer1,3, and Girish Dhall1,3; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Children’s Hospital Los Angeles, Los Angeles CA, USA; Children’s Oncology Group, Monrovia, CA, USA LGGs represent a heterogeneous group of tumors that occur across age groups and are the most common central nervous system tumors in children. AYA represent a unique subset of patients whose disease presentation, pathology and outcome often differ compared with children and adults. While differences in pediatric and adult LGGs have been established, potential differences in the presentation, pathology, and outcome of children versus AYA with LGGs have not been interrogated. We hypothesized that there are age-related differences in clinicopathological features and outcome in patients with LGGs. We performed a retrospective secondary analysis of a legacy CCG dataset (CCG9891/POG9130) to determine if differences exist between childrenand AYAwith LGGs managed primarily with surgery.Children and AYA were defined as ages 0 to 14 and 15 to 21 years, respectively. The following parameters for children (n 1⁄4 468) were compared to those of AYA (n 1⁄4 50): sex, race/ethnicity, pathological features, tumor location, incidence of seizures at presentation, level of consciousness at presentation, extent of resection, incidence of surgical complications, event-free survival (EFS), pattern of relapse and overall survival (OS). When comparing children and AYA, there were no statistically significant age-related differences in any of these clinicopathological features or EFS, OS, and pattern of relapse. In conclusion, LGGs occurring in AYA have similar clinicopathological features to those occurring in children. Our findings suggest that treatment paradigms and clinical trials for childhood LGG are appropriate for use among AYA. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.65 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The discipline of Adolescent and Young Adult (AYA) Oncology addresses compelling medical and psychosocial needs of AYA patients across the spectrum of cancer survivorship. To be successful, extraordinary collaboration involving multiple scientific disciplines and specialties is required. While AYA Oncology is international in scope, recent AYA-focused studies conducted in the Children's Oncology Group (COG) have documented survival disparities, toxicity differences, and biological insights that provide the basis for new COG trials and initiatives for this population. This experience will be useful in leveraging the new United States National Cancer Institute Clinical Trials Network to transform AYA Oncology research.

Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach.A multi-center retrospective cohort analysis was conducted of AML survivors diagnosed from 2004 to 2009 and treated with MRC-based regimens. Change in left ventricular shortening fraction (LVSF) on echocardiogram was determined from baseline to latest post-treatment/pre-relapse value; associations with potential predictors were examined.This cohort of pediatric survivors (n = 52) was assessed at a median interval of 13 months from end of treatment. Mean cumulative anthracycline dose was 339 ± 14 mg/m(2) . Mean baseline and post-treatment LVSF were 39.3 ± 0.8% and 35.4 ± 0.9%, respectively; mean percent change for individuals was -8.4 ± 2.8% (P0.001). Cardiac-directed medications were initiated in four patients (7.7%). Decline in LVSF was significantly associated with cumulative anthracycline dose, increasing BMI and Hispanic ethnicity.Early, significant decline in LVSF was observed following treatment with these MRC-based regimens. Elevated BMI and Hispanic ethnicity were identified as new independent risk factors. Children and adolescents so treated are at substantial risk for late-onset cardiomyopathy, require monitoring with annual echocardiogram per current COG survivorship guidelines, and are good candidates for appropriate cardioprotection strategies.

Purpose Children with cancer experience significant toxicities while undergoing treatment. Documentation of adverse events (AEs) in clinical trials is mandated by federal agencies. Although many AEs are subjective, the current standard is clinician reporting. Our long-term goal is to create and validate a self-report measure of subjective AEs for children aged 7 years and older that will inform AE reporting for the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). This content validation study aimed to identify which of the AEs in the current CTCAE should be included in a pediatric self-report measure. Methods We sought expert panel review and consensus among 187 pediatric clinicians from seven Children's Oncology Group institutions to determine which of the 790 AEs are amenable to child self-report. Two survey iterations were used to identify suitable AEs, and clinician agreement estimated by the content-validity ratio (CVR) was assessed. Results Response rates for surveys 1 and 2 were 72% and 67%, respectively. After the surveys, 64 CTCAE terms met the criteria of being subjective, relevant for use in pediatric cancer trials, and amenable to self-report by a child. The most frequent reasons for removal of CTCAE terms were that they relied on laboratory or clinical measures or were not applicable to children. Conclusion The 64 CTCAE terms will be translated into child-friendly terms as the basis of the child-report toxicity measure. Ultimately, systematic collection of these data will improve care by enhancing the accuracy and completeness of treatment toxicity reports for childhood cancer. Pediatr Blood Cancer 2013; 60: 1231–1236. © 2013 Wiley Periodicals, Inc.

Childhood cancer survivors who have received treatment with anthracyclines are at risk for developing cardiomyopathy in dose-dependent fashion. Historically, restrictions on certain types of physical activity that were intended to preserve cardiac function have been recommended, based on a mixture of evidence-based and consensus-based recommendations. In the LIFE Cancer Survivorship & Transition Program at Children’s Hospital Los Angeles, the authors reevaluated their recommendations for exercise in survivors who were exposed to anthracyclines, with or without irradiation in proximity to the myocardium. The primary goal was to develop consistent, specific, practical, safe, and (where possible) evidence-based recommendations for at-risk survivors in the program. To accomplish this, the authors referred to current exercise guidelines for childhood cancer survivors, consulted recent literature for relevant populations, and obtained input from the program’s pediatric cardiology consultant. The resulting risk-based exercise recommendations are designed to complement current published guidelines, maximize safe exercise, and help childhood cancer survivors return to a normal life that emphasizes overall wellness and physical activity. This article describes a single institution’s experience in modifying exercise recommendations for at-risk childhood survivors and includes the methods, findings, and current institutional practice recommendations along with sample education materials.

Purpose Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm2. Tumor location in the thalamus was also associated with poor OS. Conclusion The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

To describe survivorship services provided by the Children's Oncology Group (COG), an assessment of services was undertaken. Our overall aims were (1) to describe survivorship services, including the extent of services provided, resources (personnel, philanthropy, and research funding), billing practices, and barriers to care and 2) to describe models of care that are in use for childhood cancer survivors and adult survivors of childhood cancer.One hundred seventy-nine of 220 COG institutions (81%) completed an Internet survey in 2007.One hundred fifty-five (87%) reported providing survivorship care. Fifty-nine percent of institutions provide care for their pediatric population in specialized late effects programs. For adult survivors, 47% of institutions chose models of care, which included transitioning to adult providers for risk-based health care, while 44% of institutions keep survivors indefinitely at the treating institution (Cancer Center Based Model without Community Referral). Sixty-eight percent provide survivors with a copy of their survivorship care plan. Only 31% of institutions provide a detailed summary of results after each clinic visit, and 41% have a database to track survivor health outcomes. Minimal time required for initial and annual survivorship visits is estimated to be approximately 120 and 90 min, respectively. The most prevalent barriers to care were the lack of dedicated time for program development and a perceived insufficient knowledge on the part of the clinician receiving the transition referral.Not all COG institutions provide dedicated survivorship care, care plans, or have databases for tracking outcomes. Transitioning to adult providers is occurring within the COG. Survivorship care is time intensive.

Purpose Young adult survivors of childhood and adolescent cancer are an ever-growing population of patients, many of whom remain at lifelong risk for potentially serious complications of their cancer therapy. Yet research shows that many of these older survivors have deficient health-related knowledge and are not engaging in recommended health promotion and screening practices that could improve their long-term outcomes. The purpose of this review is to address these disparities by discussing how formal transition of care from pediatric to adult-focused survivorship services may help meet the unique medical, developmental, and psychosocial challenges of these young adults. Design Literature review and discussion. Results This article summarizes current research documenting the medical needs of young adult survivors, their suboptimal compliance with recommended follow-up, and the rationale, essential functions, current models, and innovative approaches for transition of follow-up care. Conclusion Systematic health care transition constitutes the standard of care for young adult survivors of childhood cancer. In developing a transitional care program, it is necessary to consider the scope of services to be provided, available resources, and other local exigencies that help determine the optimal model for use. Additional research is needed to improve health services delivery to this population. Effective advocacy is needed, particularly in the United States, to ensure the availability of uninterrupted health insurance coverage for survivorship services in young adulthood.

Every year in the United States, over 2,100 children die of progressive cancer, or of complications related to the disease or its treatment. Physicians, other clinicians, and parents caring for these children are often faced with decisions about the continuation or termination of life-sustaining treatment (LST). In adults, a consensus has emerged which holds that LST may be ethically discontinued if the burdens of continued treatment outweigh its benefits for the patient. While this standard is also applicable to LST decisions in pediatric oncology, its appropriate use must address several medical and ethical issues characteristic of children with cancer. These special considerations, which are the subject of this discussion, include the extensive medical experience of children with cancer, the nature of modern oncology treatment, the unpredictable patterns of response to treatment, the parent and/or physician biases which may threaten the child's well-being, the distinction between being incurably ill and imminently dying, the need for effective palliative care, and the variable levels of cognitive and emotional development which determine a child's capacity for participating in an LST decision. Consideration of these factors facilitates a consistent approach to these difficult decisions which is both compatible with current ethical guidelines and responsive to the particular needs of these patients.

Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease. Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3–43 months old (median 13 months) with minimal acid α-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort. Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid α-glucosidase; no patients withdrew from the study because of safety concerns. Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence.

Children with cancer frequently have associated cachexia and malnutrition. Failure to thrive affects nearly 40% of oncology patients with advanced or progressive disease. Malnutrition can erode quality of life and adversely impact disease prognosis. Appetite stimulation and increased food intake is 1 approach to combat cancer-related cachexia.Cyproheptadine hydrochloride (CH), an appetite stimulant, was administered to children with cancer-associated cachexia to prevent further weight loss. All participants started CH and were evaluated for response after 4 weeks. Efficacy of megestrol acetate (MA) was evaluated in patients who did not respond to CH. Medical evaluation, weight measurements, prealbumin, and serum leptin levels were preformed at follow-up visits.Seventy patients were enrolled. Of the 66 evaluable patients, 50 demonstrated a response to CH (average weight gain 2.6 kg and mean weight-for-age z-score change of 0.35, P=0.001). Seven of the 16 nonresponders received MA. Six patients completed 4 weeks of MA, 5 responded (average weight gain of 2.5 kg). The most commonly reported side effect of CH was drowsiness. One patient on MA developed low cortisol levels and hyperlipidemia.This study demonstrates that CH is a safe and effective way to promote weight gain in children with cancer/treatment-related cachexia.

The fundamental purposes underlying formal health care transition from the pediatric to adult setting for young adult survivors of childhood cancer are to facilitate the continuous, medically and developmentally appropriate implementation of risk-based guidelines for the monitoring and management of late effects of childhood cancer and its treatment; and to support the normal maturational processes involved with growing from childhood to adulthood. To achieve these, this article identifies specific goals and action items in the following key areas: Models of Transitional Care, Survivor/Family Education, Post-Transitional Care Outcomes, Education of Health Care Professionals, and Health Care Policy and Advocacy.

Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with “higher risk” acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 × 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/ or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P < .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.