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Survivors of pediatric acute lymphoblastic leukemia (ALL) often have altered body composition secondary to treatment effects, including sarcopenic obesity (SO), which increases the risk of both metabolic complications and frailty. SO is difficult to detect without using advanced imaging techniques to which access is often limited. To explore whether common clinical indices can reliably identify the presence of SO in a cohort of long-term survivors of ALL, the discriminatory capacity of body mass index (BMI) or triponderal mass index (TMI, kg/m3) for detecting SO was assessed. Thresholds of BMI and TMI associated with overweight or obesity status had poor sensitivity (<50%) and specificity for detecting SO. Total misclassification rates at these thresholds exceeded 50% and positive likelihood ratios were nonsignificant. Notably, TMI is more strongly correlated with elevated adiposity than is BMI in this survivor population (R2=0.73 vs. 0.57), suggesting further exploration is warranted. Our study is limited by the sample size, precluding detailed regression analysis. This study highlights the challenges of identifying SO in survivors of pediatric ALL using common clinical indices. Prospective evaluation of additional potential surrogate markers in survivors, in conjunction with the component features of SO, should be a key focus of future research.

Survival of cancer in childhood is increasingly common with modern therapeutic protocols but leads frequently to adverse long-term impacts on health, including metabolic and cardiovascular disease. Changes in body composition, especially an increase in fat mass and a decrease in muscle mass, are found early in patients with pediatric cancer, persist long after treatment has been completed and seem to contribute to the development of chronic disease. This review details the effects of such changes in body composition and reviews the underlying pathophysiology of the development of sarcopenic obesity and its adverse metabolic impact. The authors discuss the particular challenges in identifying obesity accurately in survivors of pediatric cancer using available measurement techniques, given that common measures, such as body mass index, do not distinguish between muscle and adipose tissue or assess their distribution. The authors highlight the importance of a harmonized approach to the assessment of body composition in pediatric cancer survivors and early identification of risk using “gold-standard” measurements. This will improve our understanding of the significance of adiposity and sarcopenia in this population, help identify thresholds predictive of metabolic risk, and ultimately prevent or ameliorate the long-term metabolic and cardiovascular impacts on health experienced by survivors of cancer in childhood.

Supplemental Digital Content is available in the text.Body size influences bone mineral density (BMD) in health. Relationships of BMD with body mass index, fat mass (FM), fat-free mass, and appendicular lean mass were explored in acute lymphoblastic leukemia (ALL) survivors (n=75; 41 males; 45 standard risk ALL) >10 years from diagnosis. Dual energy radiograph absorptiometry performed body composition analysis. Relationships were assessed by regression analyses and Pearson correlation coefficients (r). Twenty subjects (26.3%) were osteopenic; lumbar spine (LS) BMD Zscore <−1.00. Age at diagnosis, sex, ALL risk-category, type of post-induction steroid or cranial radiation did not correlate with LS or whole body (WB) BMD. Body mass index correlated significantly with LS BMD (r=0.333, P=0.004) and WB BMD (r=0.271, P=0.033). FM index (FM/height²) Zscore showed no significant correlation with LS or WB BMD. Fat-free mass index Zscore correlated strongly with LS BMD (r=0.386, P=0.013) and WB BMD (r=0.605, P<0.001) in males but not in females. The appendicular lean mass index, a surrogate for skeletal muscle mass, correlated significantly with LS BMD (r=0.367, P=0.018) and WB BMD (r=0.604, P<0.001) in males but not in females. Future studies to evaluate interventions to enhance BMD focused on improving body composition particularly skeletal muscle mass are warranted.

Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium. The median age was 21.15 years and time from diagnosis 15.07 years, and 27 subjects had experienced fractures. More than 30% of the total sample were OW/OB. There was no correlation of body mass index with present PA. There were no significant differences between those with/without fractures in terms of age, sex, time from diagnosis, and the prevalence of OW/OB. Subjects with fractures during treatment reported more total activity on typical weekend days than those without fractures (mean 8.8 vs. 6.9 h, P<0.01). There was no significant difference on weekdays. Higher activity on weekends suggests that fractures may have occurred more commonly in those who had a more active lifestyle before, during, and after treatment.

Survivors of brain tumors in childhood experience adverse sequelae that are greater in prevalence and severity than those encountered by survivors of all other forms of cancer in early life, reflected in a burden of morbidity by instruments measuring health-related quality of life (HRQL). However, there are few studies of the change in HRQL over time in such populations. Patients who were above 5 years of age, at least 2 years from completion of therapy, and able to communicate in English were eligible for study of HRQL by the Health Utilities Index HUI2 and HUI3 at study entry, and again 5 and 10 years later. An initial cohort of 40 patients was reduced to 37 and 25 at the second and third time points, respectively, although only 1 death occurred during the study. HRQL showed a progressive decline over the decade, reaching conventional levels of clinical significance for the sizes of the changes. Median scores for HUI2 were 0.93, 0.90, and 0.88; and for HUI3 were 0.88, 0.85, and 0.77 at baseline, 5, and 10 years, respectively. The serial decline in HRQL demands further examination and an exploration of potential targets for therapeutic intervention.

This position statement from the Canadian Task Force on Adolescents and Young Adults with cancer aims to (1) conceptualize the numerous transition experiences encountered by adolescents and young adults (AYA) with cancer; and (2) provide recommendations on how to help the AYA regain a sense of control over their lives as they adjust to these transition experiences.

Delay in diagnosis is a pejorative term for an interval better described as lag time, a period of considerable concern to health care administrators, providers, and consumers, receiving attention in numerous countries over many years. The general assumption that the longer the lag time the poorer the prospect for survival is not supported by the evidence that points to a more complex relationship. In some instances shorter lag times are associated with longer survival and in others correlate with shorter survival; in many instances there is no clear relationship. The associations between numerous demographic variables, such as the patient’s age and the nature of the first health care contact, and lag time account for no more than 20 of the variance in this interval. It appears that more important determinants are the biology of the tumor and its related clinical behavior. Nevertheless, to minimize anxiety in patients and families, every effort should be made to reach a timely diagnosis. With the exceptions of retinoblastoma and malignant melanoma, campaigns to enhance public awareness have met with limited success with regard to reducing lag times in children and adolescents with cancer, indicating a challenge worthy of international attention.

The bone health of adults is dependent on the appropriate acquisition of peak bone mineral mass during late childhood and adolescence. Measurement of bone mineral density (BMD) in clinical practice is accomplished usually by dual energy x-ray absorptiometry that provides 2-dimensional (areal) values for BMD, does not distinguish cortical from trabecular bone, and should be adjusted for height and weight when used for children and adolescents. Peripheral quantitative computed tomography (pQCT) provides volumetric measures of BMD and geometry in both cortical and trabecular bone and, unlike dual energy x-ray absorptiometry, does not need adjustment for body size. Studies of bone health in young people require reference data for normative comparison. A literature review from 1946 to 2012 identified 1886 titles suggesting use of pQCT, with only 32 reporting some form of normative data. A detailed review of these 32 reports revealed a lack of consensus among users for standard scan locations in upper and lower limbs, acquisition protocols and analytical steps, and variables reported. Meaningful and effective use of pQCT for assessing bone strength and overall bone health in all age groups will require better defined normative data derived with common measuring techniques, equipment, and analytical approaches.

Maintenance of adequate nutrition is important in the care of children with cancer. In clinical practice, determination of nutritional status can be accomplished with measurement of body composition by dual-energy x-ray absorptiometry (DXA). However, DXA is seldom available in low-income countries where most children with cancer live. This study sought to provide predictive equations for lean body mass and fat mass, measured by DXA, on the basis of simple arm anthropometry providing measures of mid-upper arm circumference and triceps skin-fold thickness in a population (N=99) of children diagnosed with cancer. Such equations were derived successfully with the inclusion of absolute body weight, the body weight Z-score, and the predicted whole-body bone mineral content on the basis of age and sex. Attempted validation in a small sample (N=7) of children who completed therapy for acute lymphoblastic leukemia revealed disparities reflective of the prevalence of obesity in such survivors. Further validation must be undertaken in large samples of children with a variety of malignant diseases to assess the robustness of the equations predictive of body composition.

Children with acute lymphoblastic leukemia experience musculoskeletal morbidity during therapy. We examined the patterns of change in skeletal muscle mass (SMM) and the relationship between change in SMM and the burden of illness as reflected in days of hospitalization. Ninety-one children had dual energy x-ray absorptiometry (DXA scans) during treatment, yielding the sum of lean tissue mass in all 4 limbs; the appendicular lean mass. SMM was derived from appendicular lean mass. The number of inpatient days was recorded. DXA scans at 5 time points showed a profile of change in SMM characterized by a drop in the mean Zscore from −0.18 at diagnosis to −1.08 after 6 months of therapy, with a partial recovery 12 to 24 months after diagnosis. Levels of serum creatinine, a surrogate measure of SMM, were mainly unchanged. The extent of the drop in SMM during early therapy was associated with the duration of hospitalization (r=0.31, P<0.05). Children with acute lymphoblastic leukemia experience a notable reduction in SMM early in treatment, with incomplete recovery. The degree of loss is associated with the burden of illness. These findings provide a target for a therapeutic intervention and a measure to determine its efficacy.

Chromosome 1 is the largest of all human chromosomes, containing 3141 genes. It is linked to 890 known genetic diseases including congenital hypothyroidism, hemochromatosis, and prostate cancer. Recognized deletion and duplication syndromes have been described. Deletions in the short arm (p) of the chromosome have been identified in tumors of the brain and kidneys. Duplications in the long (q) arm of the chromosome are reported in myelodysplastic syndromes. Solitary 1p36 deletion or 1q42 duplication are rarely reported entities and their associations with malignancy have not been characterized. We report a case of a child with constitutional 1pter-p36.31 duplication and 1q43-qter deletion who developed acute lymphoblastic leukemia (ALL). The patient’s oncologic presentation and subsequent clinical course raise the question of the association of the underlying genetic abnormality and its malignant potential, specifically in relation to ALL. Acquired chromosome 1 deletions and duplications have been well described in other malignant diseases. Constitutional chromosome 1p duplication and 1q deletions have not been described with ALL.

The nutritional status of children with cancer is clinically important. In an effort to separate the influences of disease and treatment, we studied children at the time of diagnosis. A total of 99 children underwent assessment by 24 hours dietary recall, measurement of body mass index (BMI), and analysis of body composition by dual energy x-ray absorptiometry (DXA scan). The group averages for calorie intake and BMI were close to the median population norms but ranged widely among individuals. As a group the study participants exceeded the Dietary Reference Intake for protein. Nine children (9) had a BMI

Obesity is increasingly prevalent in affluent societies and portends considerable morbidity. This is especially true in children with acute lymphoblastic leukemia (ALL) in whom the metabolic syndrome may begin during therapy, demanding clarification of the trajectory of weight gain so that effective interventions may be developed. In this retrospective study of body mass index from a single institution over a 20-year period, almost 15 of children with ALL were at risk of overweight or frankly overweight (body mass index >85th centile) at diagnosis. This proportion increased steadily, reaching 40 at the end of treatment. Strategies to limit weight gain will have to be instituted early in the management of children with ALL, and will probably have to be maintained throughout and after the completion of active treatment.

Camping programs for children with chronic diseases are designed for specific needs, but rigorous evaluation of their impact is largely lacking. The biggest camp for children with cancer and their families provided an opportunity to conduct such an investigation.

Osteopenia is a common consequence of the treatment of acute lymphoblastic leukemia (ALL) in children and adolescents, due predominantly to glucocorticosteroid therapy. The pathogenesis relates to an imbalance of resorption over formation of bone.

The objectives were to describe and compare waiting times to diagnosis and treatment of children and adolescents who accessed pediatric oncology centers in Canada for healthcare, and to assess the effects and relative contributions of age, sex, and diagnosis to waiting times.

Cancer is the commonest cause of disease-related death in children over 5 years of age in various parts of Latin America, but the survival rates are improving. This study assessed the health status and health-related quality of life (HRQL) of more than 200 survivors of cancer in childhood in the countries of a Central American consortium devoted to pediatric hematology-oncology. Patients' self-reports and parental proxy assessments were collected using interviewer-administered Spanish-language questionnaires, and physicians provided assessments using self-complete questionnaires, based on the complementary Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems. Inter-rater agreement, measured by intra-class correlation (ICC), was fair to moderate (0.340.60) for all 3 pairs of assessors for readily assessable attributes HUI2 sensation, HUI3 vision, HUI3 hearing, and HUI3 ambulation. Less than 40 of the patients reported being in perfect health. More than 20 reported being in health states with HRQL scores corresponding to moderate or severe disability, notably in the attributes of emotion and cognition. The results reflect a common profile in survivors of cancer in childhood, including those from industrialized societies. This study illustrates the feasibility of collecting reliable and valid information on HRQL in the developing country context, raising the prospect that such information could be used to influence clinical practice.

This report describes the clinical course of three siblings, all of whom had Evans syndrome in childhood.

In the period 1980–1988, data were collected (prospectively from 1985) on the clinical utilization of exteriorized, tunnelled, right atrial catheters in children with cancer undergoing treatment at a single institution. A total of 231 devices were placed in 180 patients. Individual catheters were in place for a median of 314 days, with a total experience of more than 83,000 days. This form of long-term venous access was used for the administration of antineoplastic agents and other drugs, blood products (especially platelet concentrates and packed red blood cells), parenteral nutrition and infusion of other fluids, obtaining samples of venous blood, and giving intravenous contrast media and radiolabeled substances for radiological investigations. Almost 80 of catheters were removed electively (on completion of scheduled therapy or at death), with the remainder requiring removal in the management of infection or device displacement. Infections were manifest in two-thirds of the children, most commonly (60) at the catheter exit site on the anterior chest wall. “Clinically significant” infection occurred with a frequency of 2.1 episodes per 1,000 patient days, with Staphylococcal species predominating except for the circumstances of catheter colonization in which Gram-negative, water-borne organisms were most in evidence. Empirical, intravenous, combined antibiotic therapy was effective in –90 of “clinically significant” episodes. Mechanical complications (traveling, leakage, or catheter occlusion) occurred less frequently and were managed by repairing or replacing the device, or clearing the block. Indwelling catheters, of the Broviac or Hickman types, offer major advantages with acceptable morbidity in the management of children with malignant diseases.

The primary purpose of this study was to determine the therapeutic efficacy of a protocol of treatment for acute lymphoblastic leukemia (ALL) in children. A prospective approach was adopted with an inception cohort of patients. Outcome measures were assessed on December 31, 1990. The study was conducted at two tertiary care centres (pediatric oncology programs) in Ontario, Canada. All children with ALL were eligible for study and consecutive recruitment took place between May 1984 and July 1987. They were classified at diagnosis into one of three categories for risk of relapse according to standardized criteria. Thirty-nine children were designated as having standard risk (SR), 31 as having high risk (HR), and 12 as having very high risk (VHR) disease. All patients are included in the analysis. Treatment was administered according to risk category-specific chemotherapy protocols, the details of which have been published. A distinguishing feature of these strategies is the intensive use of intramuscular L-asparaginase. Patients remained on these regimens for 2 years or until relapse or toxic death (events) ensued. Total and event-free survival data were determined by life-table analysis (Kaplan-Meier plots). With a minimum interval from diagnosis of 186 weeks and a median interval exceeding 5 years, the cumulative proportion of the entire cohort (C) surviving is 85 [95 confidence interval (CI), 77–93]. For the respective risk groups, the corresponding proportions are SR 94 (95 CI, 87–100), HR 74 (95 CI, 59–89), and VHR 81 (95 CI, 59–100). Event-free survival data are C 76 (95 CI, 67–85), SR 89 (95 CI, 79–99), HR 69 (95 CI, 53–85), and VHR 67 (95 CI, 40–94). Because 14 of the 17 events occurred before the minimum follow-up period, the majority of children with ALL treated on these protocols are now on the plateau of the event-free survival curve, and so are probably cured.

Xanthoma disseminatum is a rare non-Langerhans' histiocytosis of older children and adults with characteristic lesions involving the skin, mucous membrane and occasionally internal organs. We describe a case, presenting in infancy, with unique clinical features.

Monozygotic twin boys presented at 1 year of age with seborrheic skin rash, otorrhea, and hepatosplenomegaly. Skin biopsy confirmed Langerhans cell histiocytosis. Treatment with conventional antineoplastic drugs and with calf thymus extract was ineffective. The disease remained refractory to recombinant human a-interferon and to low-dose total body irradiation, and the children died between 3 and 3 years of age.

The purpose of this study is to assess the effects of amikacin on renal proximal tubular function, and on magnesium (Mg) and calcium (Ca) status in children treated for acute lymphoblastic leukemia (ALL).

Three groups of patients were studied to assess the effect of oral corticosteroid therapy on erythropoiesis in vivo as measured by changes in haemoglobin concentration (Hb) and red blood cell count (RBC). Fifteen patients with acute lymphoblastic leukaemia, who were in remission and receiving pulses of vincristine and prednisone during maintenance chemotherapy, showed no rise in Hb or RBC with steroid therapy. Likewise, 15 patients completing chemotherapy for ALL did not show a rise in Hb or RBC after stopping treatment. However, 14 children with acute immune thrombocytopenic purpura demonstrated a significant increase in Hb and RBC during a course of treatment with prednisone. These findings complement the results of in vitro studies, indicating that erythropoiesis in normal human bone marrow is stimulated by corticosteroid therapy.