Dietary supplement use among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. METHODS: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. RESULTS: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well-being and vitality were positively associated with supplement use among childhood cancer survivors. CONCLUSIONS: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors.

Immunogenicity and safety of the human papillomavirus vaccine in young survivors of cancer in the USA: a single-arm, open-label, phase 2, non-inferiority trial.

BACKGROUND: Young survivors of cancer are at increased risk for cancers that are related to human papillomavirus (HPV), primarily caused by oncogenic HPV types 16 and 18. We aimed to examine the immunogenicity and safety of the three-dose series of HPV vaccine in young survivors of cancer. METHODS: We conducted an investigator-initiated, phase 2, single-arm, open-label, non-inferiority trial at five National Cancer Institute-designated comprehensive cancer centres in the USA. Eligible participants were survivors of cancer who were HPV vaccine-naive, were aged 9-26 years, in remission, and had completed cancer therapy between 1 and 5 years previously. Participants received three intramuscular doses of either quadrivalent HPV vaccine (HPV4; enrolments on or before March 1, 2016) or nonavalent HPV vaccine (HPV9; enrolments after March 1, 2016) over 6 months (on day 1, at month 2, and at month 6). We also obtained data from published clinical trials assessing safety and immunogenicity of HPV4 and HPV9 in 9-26-year-olds from the general population, as a comparator group. The primary endpoint was antibody response against HPV types 16 and 18 at month 7 in the per-protocol population. A response was deemed non-inferior if the lower bound of the multiplicity-adjusted 95% CI was greater than 0·5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titres (GMTs) in survivors of cancer versus the general population. Responses were examined separately in male and female participants by age group (ie, 9-15 years and 16-26 years). Safety was assessed in all participants who received at least one vaccine dose and for whom safety data were available. This study is registered with ClinicalTrials.gov, NCT01492582. This trial is now completed. FINDINGS: Between Feb 18, 2013, and June 22, 2018, we enrolled 453 survivors of cancer, of whom 436 received one or more vaccine doses: 203 (47%) participants had survived leukaemia, 185 (42%) were female, and 280 (64%) were non-Hispanic white. Mean age at first dose was 15·6 years (SD 4·6). 378 (83%) of 453 participants had evaluable immunogenicity data; main reasons for exclusion from per-protocol analysis were to loss to follow-up, patient reasons, and medical reasons. Data were also obtained from 26 486 general population controls. The ratio of mean GMT for anti-HPV types 16 and 18 in survivors of cancer versus the general population was more than 1 for all subgroups (ie, aged 9-15 years, aged 16-26 years, male, and female groups) in both vaccine cohorts (ranging from 1·64 [95% CI 1·12-2·18] for anti-HPV type 16 in female participants aged 9-15 years who received HPV9, to 4·77 [2·48-7·18] for anti-HPV type 18 in male participants aged 16-26 years who received HPV4). Non-inferiority criteria were met within each age and sex subgroup, except against HPV type 18 in female participants aged 16-26 years receiving HPV9 (4·30 [0·00-9·05]). Adverse events were reported by 237 (54%) of 435 participants; injection site pain was most common (174 [40%] participants). One serious adverse event (ie, erythema nodosum) was possibly related to vaccine (HPV9; 16-26 year female cohort). INTERPRETATION: Immunogenicity and safety of HPV vaccine three-dose series in survivors of cancer is similar to that in the general population, providing evidence for use in this clinically vulnerable population. FUNDING: US National Cancer Institute, Merck, Sharp & Dohme, and American Lebanese Syrian Associated Charities.

Sexual behaviors and human papillomavirus vaccine non-initiation among young adult cancer survivors.

BACKGROUND: Young adult cancer survivors are at risk for subsequent human papillomavirus (HPV)-related malignancies. High-risk sexual behavior increases risk for HPV acquisition; HPV vaccination protects against infection. We aimed to determine the prevalence of sexual behaviors, factors related to high-risk sexual behaviors, and the relationship between sexual behaviors and HPV vaccine non-initiation among survivors. METHODS: Survivors at comprehensive cancer centers, aged 18-26 years and 1-5 years post-treatment, reported sexual behaviors and HPV vaccine initiation (i.e., ≥ 1 dose). Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with high-risk sexual behaviors (age at first intercourse < 16 years, ≥ 3 lifetime sexual partners, or condom use ≤ 50% of the time) and to explore the relationship between sexual behaviors and vaccine non-initiation. RESULTS: Of the 312 participants (48.1% female, median age at cancer diagnosis 17.2 years and at survey 20.9 years), sexual intercourse was reported by 63.1%. Of those reporting intercourse, 74.6% reported high-risk sexual behavior. Factors related to high-risk sexual behavior included currently dating/partnered (OR = 4.39, 95%CI 2.5-7.7, P < 0.001) and perceived susceptibility to HPV (OR = 1.76, 95%CI 1.3-2.5, P < 0.001). Most survivors (75.3%) reported HPV vaccine non-initiation; sexual behaviors were not associated with vaccine non-initiation (P = 0.4). CONCLUSIONS: Many survivors participate in high-risk sexual behaviors, yet HPV vaccine initiation rates are low. Factors related to high-risk sexual behaviors can inform interventions to reduce risk for HPV acquisition among survivors. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors participate in sexual behaviors that increase risk for HPV acquisition and would benefit from vaccination.

Connectivity of the Cerebello-Thalamo-Cortical Pathway in Survivors of Childhood Leukemia Treated With Chemotherapy Only.

Importance: Treatment with contemporary chemotherapy-only protocols is associated with risk for neurocognitive impairment among survivors of childhood acute lymphoblastic leukemia (ALL). Objective: To determine whether concurrent use of methotrexate and glucocorticoids is associated with interference with the antioxidant system of the brain and damage and disruption of glucocorticoid-sensitive regions of the cerebello-thalamo-cortical network. Design, Setting, and Participants: This cross-sectional study was conducted from December 2016 to July 2019 in a single pediatric cancer tertiary care center. Participants included survivors of childhood ALL who were more than 5 years from cancer diagnosis, age 8 years or older, and treated on an institutional chemotherapy-only protocol. Age-matched community members were recruited as a control group. Data were analyzed from August 2017 to August 2020. Exposure: ALL treatment using chemotherapy-only protocols. Main Outcomes and Measures: This study compared brain volumes between survivors and individuals in a community control group and examined associations among survivors of methotrexate and dexamethasone exposure with neurocognitive outcomes. Functional and effective connectivity measures were compared between survivors with and without cognitive impairment. The Rey-Osterrieth complex figure test, a neurocognitive evaluation in which individuals are asked to copy a figure and then draw the figure from memory, was scored according to published guidelines and transformed into age-adjusted z scores based on nationally representative reference data and used to measure organization and planning deficits. ß values for neurocognitive tests represented the amount of change in cerebellar volume or chemotherapy exposure associated with 1 SD change in neurocognitive outcome by z score (mm3/1 SD in z score for cerebellum, mm3/[g×hr/L] for dexamethasone and methotrexate AUC, and mm3/intrathecal count for total intrathecal count). Results: Among 302 eligible individuals, 218 (72%) participated in the study and 176 (58%) had usable magnetic resonance imaging (MRI) results. Among these, 89 (51%) were female participants and the mean (range) age was 6.8 (1-18) years at diagnosis and 14.5 (8-27) years at evaluation. Of 100 community individuals recruited as the control group, 82 had usable MRI results; among these, 35 (43%) were female individuals and the mean (range) age was 13.8 (8-26) years at evaluation. There was no significant difference in total brain volume between survivors and individuals in the control group. Survivors of both sexes showed decreased mean (SD) cerebellar volumes compared with the control population (female: 70 568 [6465] mm3 vs 75 134 [6780] mm3; P < .001; male: 77 335 [6210] mm3 vs 79 020 [7420] mm3; P < .001). In female survivors, decreased cerebellar volume was associated with worse performance in Rey-Osterrieth complex figure test (left cerebellum: ß = 55.54; SE = 25.55; P = .03; right cerebellum: ß = 52.57; SE = 25.50; P = .04) and poorer dominant-hand motor processing speed (ie, grooved pegboard performance) (left cerebellum: ß = 82.71; SE = 31.04; P = .009; right cerebellum: ß = 91.06; SE = 30.72; P = .004). In female survivors, increased number of intrathecal treatments (ie, number of separate injections) was also associated with Worse Rey-Osterrieth test performance (ß = -0.154; SE = 0.063; P = .02), as was increased dexamethasone exposure (ß = -0.0014; SE = 0.0005; P = .01). Executive dysfunction was correlated with increased global efficiency between smaller brain regions (Pearson r = -0.24; P = .01) compared with individuals without dysfunction. Anatomical connectivity showed differences between impaired and nonimpaired survivors. Analysis of variance of effective-connectivity weights identified a significant interaction association (F = 3.99; P = .02) among the direction and strength of connectivity between the cerebellum and DLPFC, female sex, and executive dysfunction. Finally, no effective connectivity was found between the precuneus and DLPFC in female survivors with executive dysfunction. Conclusions and Relevance: These findings suggest that dexamethasone exposure was associated with smaller cerebello-thalamo-cortical regions in survivors of ALL and that disruption of effective connectivity was associated with impairment of executive function in female survivors.

Patient-reported outcomes in paediatric cancer survivorship: a qualitative study to elicit the content from cancer survivors and caregivers.

OBJECTIVES: Content elucidation for patient-reported outcomes (PROs) in paediatric cancer survivorship is understudied. We aimed to compare differences in the contents of five PRO domains that are important to paediatric cancer survivorship through semistructured interviews with paediatric cancer survivors and caregivers, and identified new concepts that were not covered in the item banks of the Patient-Reported Outcomes Measurement Information System (PROMIS). DESIGN: Semistructured interviews to collect qualitative PRO data from survivors and caregivers. SETTING: A survivorship care clinic of a comprehensive cancer centre in the USA. PARTICIPANTS: The study included 51 survivors (<18 years old) and 35 caregivers who completed interviews between August and December 2016. Content experts coded the transcribed interviews into 'meaningful concepts' per PROMIS item concepts and identified new concepts per a consensus. Frequencies of meaningful concepts used by survivors and caregivers were compared by Wilcoxon rank-sum test. RESULTS: For pain and meaning and purpose, 'Hurt a lot' and 'Purpose in life' were top concepts for survivors and caregivers, respectively. For fatigue and psychological stress, 'Needed to sleep during the day'/'Trouble doing schoolwork' and 'Felt worried' were top concepts for survivors, and 'Felt tired' and 'Felt distress'/'Felt stressed' for caregivers. Survivors reported more physically relevant contents (eg, 'Hard to do sport/exercise'; 0.78 vs 0.23, p=0.007) for pain, fatigue and stress, whereas caregivers used more emotionally relevant concepts (eg, 'Too tired to enjoy things I like to do'; 0.31 vs 0.05, p=0.025). Both groups reported positive thoughts for meaning and purpose (eg, 'Have goals for myself'). One (psychological stress, meaning and purpose) to eleven (fatigue) new concepts were generated. CONCLUSIONS: Important PRO contents in the form of meaningful concepts raised by survivors and caregivers were different and new concepts emerged. PRO measures are warranted to include survivorship-specific items by accounting for the child's and the caregiver's viewpoints.

Protein Supplementation and Resistance Training in Childhood Cancer Survivors.

PURPOSE: Muscle weakness, low lean body mass, and poor physical performance are prevalent among adult survivors of childhood cancer (survivors). We evaluated the feasibility and effects of resistance training with and without protein supplementation on lean body mass and muscle strength among survivors. METHODS: This double-blind placebo-controlled trial enrolled survivors ≥18 to <45 yr old. Participants were randomized to resistance training with protein supplement (21 g whey protein per day, 90 kcal) (RT + S) or resistance training with placebo (sucrose, 90 kcal) (RT + P). Participants received educational materials, access to a local fitness center, and a tailored resistance training program with tapered supervision. Participant retention and adherence were used to evaluate feasibility. Lean body mass and muscle strength were assessed at baseline and 24 wk, using dual x-ray absorptiometry, and dynamometer testing or one-repetition maximum testing, respectively. Mean changes were compared with two-way ANOVA. RESULTS: Of 70 participants randomized, 57 completed the 24-wk intervention (24 in RT + S, 33 in RT + P). The RT + S group completed 74.8% and the RT + P group completed 67.0% of exercise sessions. Mean ± SD age for those who completed was 33.1 ± 7.0 yr, 67% were White and 47% female. There were no differences in change in lean mass (RT + S, 1.05 ± 2.34 kg; RT + P, 0.13 ± 2.19 kg; P = 0.10) or strength (grip RT + S, 1.65 ± 4.17 kg; RT + P, 1.63 ± 4.47 kg; P = 0.98; mean leg press RT + S, 58.4 ± 78.8 kg; RT + P, 51.0 ± 65.1 kg; P = 0.68) between groups. Both lean mass (P = 0.03) and strength (grip P = 0.003, leg press P < 0.001) increased over time. CONCLUSIONS: Supervised resistance training among survivors with protein supplementation is feasible but not more effective at increasing total lean body mass than resistance training alone.

Cerebral microbleeds in adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation.

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57-10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform.

Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort.

Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited. Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes. Design: Cross-sectional. Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center. Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis. Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED). Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI. Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.

Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes.

OBJECTIVES: To estimate the prevalence of central precocious puberty (CPP) after treatment for tumours and malignancies involving the central nervous system (CNS) and examine repercussions on growth and pubertal outcomes. DESIGN: Retrospective study of patients with tumours near and/or exposed to radiotherapy to the hypothalamus/pituitary axis (HPA). PATIENTS AND MEASUREMENTS: Patients with CPP were evaluated at puberty onset, completion of GnRH agonist treatment (GnRHa) and last follow-up. Multivariable analysis was used to test associations between tumour location, sex, age at CPP, GnRHa duration and a diagnosis of CPP with final height <-2SD score (SDS), gonadotropin deficiency (LH/FSHD) and obesity, respectively. RESULTS: Eighty patients (47 females) had CPP and were followed for 11·4 ± 5·0 years (mean ± SD). The prevalence of CPP was 15·2% overall, 29·2% following HPA tumours and 6·6% after radiotherapy for non-HPA tumours. Height <-2SDS was more common at the last follow-up than at the puberty onset (21·4% vs 2·4%, P = 0·005). Obesity was more prevalent at the last follow-up than at the completion of GnRHa or the puberty onset (37·7%, 22·6% and 20·8%, respectively, P = 0·03). Longer duration of GnRHa was associated with increased odds of final height <-2SDS (OR = 2·1, 95% CI 1·0-4·3) and longer follow-up with obesity (OR = 1·3, 95% CI 1·1-1·6). LH/FSHD was diagnosed in 32·6%. There was no independent association between CPP and final height <-2SDS, and LH/FSHD and obesity in the subset of patients with HPA low-grade gliomas. CONCLUSIONS: Patients with organic CPP experience an incomplete recovery of growth and a high prevalence of LH/FSHD and obesity. Early diagnosis and treatment of CPP may limit further deterioration of final height prospects.

Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report.

PURPOSE: Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group. METHODS: An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system. RESULTS: The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment. CONCLUSIONS: Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.

Physical therapy and chiropractic use among childhood cancer survivors with chronic disease: impact on health-related quality of life.

INTRODUCTION: The use of rehabilitation services to address musculoskeletal, neurological and cardiovascular late effects among childhood cancer survivors could improve physical function and health-related quality-of-life (HRQL). We describe physical therapy (PT) and chiropractic utilization among childhood cancer survivors and their association with HRQL. METHODS: The sample included 5+ year survivors from the Childhood Cancer Survivor Study (N = 9,289). Questions addressing use of PT or chiropractic services and HRQL (Medical Outcomes Survey Short Form (SF-36)) were evaluated. Multivariable regression models compared PT and/or chiropractic utilization between survivors and siblings, and by diagnosis, treatment and demographic characteristics; associations between chronic disease, PT/chiropractic use, and HRQL were similarly evaluated. RESULTS: Survivors were not more likely to use PT (OR 1.0; 95% CI 0.8-1.2) or chiropractic (OR 0.8; 95% CI 0.7-1.0) services than siblings. More survivors reported using chiropractic (12.4%) than PT (9.2%) services. Older age and having health insurance were associated with utilization of either PT or chiropractic services. Grade 3-4 chronic conditions and a CNS tumor or sarcoma history were associated with PT but not with chiropractic service utilization. Survivors with musculoskeletal (OR 1.8; 95% CI 1.1-2.9), neurological (OR 3.4; 95% CI 1.6-6.9), or cardiovascular (OR 3.3; 95% CI 1.6-6.9) chronic conditions who used PT/chiropractic services were more likely to report poor physical health than survivors who did not use services. CONCLUSIONS: The reported prevalence of PT/chiropractic among survivors is consistent with that reported by siblings. Severity of late effects is associated with service use and with reporting poor physical health. IMPLICATIONS FOR CANCER SURVIVORS: Long-term childhood cancer survivors do not appear to utilize rehabilitation services to optimize physical function and support increased HRQL.

Health behaviors, medical care, and interventions to promote healthy living in the Childhood Cancer Survivor Study cohort.

Childhood cancer survivors are at risk for medical and psychosocial late effects as a result of their cancer and its therapy. Promotion of healthy lifestyle behaviors and provision of regular risk-based medical care and surveillance may modify the evolution of these late effects. This manuscript summarizes publications from the Childhood Cancer Survivor Study (CCSS) that have examined health behaviors, risk-based health care, and interventions to promote healthy lifestyle practices. Long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects. Nearly 90% of survivors report receiving some form of medical care. However, only 18% report medical visits related to their prior cancer that include discussion or ordering of screening tests or counseling on how to reduce the specific risks arising from their cancer. One low-cost, peer-driven intervention trial has been successful in improving smoking cessation within the CCSS cohort. On the basis of data from CCSS investigations, several trials to promote improved medical surveillance among high-risk groups within the cohort are underway. Despite their long-term risks, many survivors of childhood cancer engage in risky health behaviors and do not receive adequate risk-based medical care.

Implementing an intervention to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia: BONEII, a prospective placebo-controlled double-blind randomized interventional longitudinal study design.

The BONEII study is a large two-phase study. The baseline study (Study 1) aims to estimate the prevalence of diminished bone mineral density (BMD) in patients treated for childhood acute lymphoblastic leukemia (ALL) and identify risk factors for BMD deficits. The interventional phase (Study 2) of BONEII has a placebo-controlled double-blind randomized longitudinal design to evaluate the effects of nutritional counseling and calcium and vitamin D supplementation on changes in BMD and serum and urine markers of bone metabolism. The extensive information being collected through this large study will serve as a repository of relational data about BMD and bone turnover and will support further investigations to assess the association of calcium metabolism, bone turnover, nutritional intake, lifestyle factors (such as exercise and the use of alcohol and tobacco), and the specific agents used in ALL therapy in this rapidly increasing population of childhood cancer survivors.

Cisplatin-induced hypomagnesemia and cardiac dysrhythmia.

We describe a case of a patient with cisplatin-induced hypomagnesemia who suffered brief asystole during an episode of gastroenteritis. Structural heart disease was excluded. The patient achieved complete clinical recovery after short-term administration of intravenous magnesium supplementation. Cisplatin should be considered a cause of hypomagnesemic-related cardiac dysrhythmia. Magnesium deficit may increase myocardial electrical instability and thus, the risk of life-threatening arrhythmias and sudden death. Long-term serum electrolyte measurement and appropriate replacement of magnesium are recommended.

Retention of survivors of acute lymphoblastic leukemia in a longitudinal study of bone mineral density.

Attrition in longitudinal studies of survivors of childhood cancer reduces these studies' statistical power, introduces bias and threatens internal and external validity. This study investigated the variables associated with dropout of survivors of acute lymphoblastic leukemia in a trial investigating the effect of vitamin D and calcium supplementation and nutritional counseling on bone mineral density (BMD). Twenty-five participants withdrew from the study. Common reasons given for withdrawing were intolerance of the study drug, family hardship and schedule conflicts. Few statistically and clinically significant differences identified participants who completed the study. Nurses need to be aware of the reasons that participants withdraw from clinical trials, as they are in a strategic position to encourage patients to participate in health promotion studies.

Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: There is little information about factors modulating bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia (ALL). PROCEDURE: We analyzed data from 57 survivors (26 male, 52 Caucasian) who underwent two serial quantitative computed tomography (QCT) studies of BMD. Using multiple linear regression, we evaluated the association of BMD change with demographic variables, treatment history, hormone therapy, exercise, and tobacco and alcohol use. RESULTS: The median age was 3.4 years (range, 0.9-17.4 years) at diagnosis of ALL; the median age at the first QCT (Study I) was 15.0 years (range, 10.6-31.0 years) and at the second QCT (Study II) was 18.2 years (range, 14.2-35.3 years). Mean height increased 4.7 cm and mean weight increased 8.8 kg between Studies I and II. While the mean BMD increased 9.33 mg/cc (P = 0.003), the BMD Z-score increased only slightly (0.21 SD, P = 0.035). Cortical bone density increased significantly (approximately 25.3 mg/cc; P = 0.001), but the ratio of trabecular to cortical BMD decreased significantly (P = 0.045). Factors independently associated with unfavorable BMD changes included older age at diagnosis (P = 0.001), female sex (P = 0.018), and nutritional supplementation (0.032). Alcohol (P = 0.009) was an unfavorable factor in a univariable analysis. CONCLUSIONS: Bone mineral accretion during adolescence is attenuated in childhood ALL survivors by a comparative deficit in trabecular versus cortical bone deposition. BMD is influenced favorably by exercise in early adolescence and unfavorably by the use of nutritional supplements and alcohol. These results provide new information about behavioral factors that affect bone accrual in survivors of childhood ALL and warrant definitive evaluation in a larger cohort.