Health-related quality of life in long-term survivors of acute lymphoblastic leukemia in childhood and adolescence.

PURPOSE: Children with acute lymphoblastic leukemia (ALL), the commonest form of cancer in this age group, suffer considerable morbidity during treatment, with the majority returning to good health soon after therapy has been completed, as reflected in health-related quality of life (HRQL). However, survivors are at risk of many adverse health outcomes later, including obesity, measured by body mass index (BMI), that is compounded by limited physical activity. This study examined the HRQL of long-term survivors of ALL and its relationship to BMI and physical activity. METHODS: A cohort of 75 subjects who were more than 10 years from diagnosis was assessed for BMI (weight in kg/height in m2) and completed two questionnaires. HRQL was measured by the multi-attribute, preference-based Health Utilities Index (HUI) instrument HUI23S4.15Q designed for self-report, and physical activity was quantified by the Habitual Activity Estimation Scale. RESULTS: The mean utility scores for overall HRQL (HUI2 = 0.88, HUI3 = 0.83) were similar to those in the Canadian and US general population segments of equivalent age (HUI2 = 0.86, HUI3 = 0.85). However, the minimum scores (HUI2 = 0.23, HUI3 = -0.09) revealed a group of survivors with notable disabilities in the attributes of hearing, emotion, cognition, and pain. There were no statistically significant correlations between HRQL and BMI or between HRQL and physical activity, except for deafness and inactivity on weekdays. CONCLUSIONS: Overall, long-term survivors of ALL in childhood enjoy good HRQL but some experience appreciable disability, though this is not associated with BMI or, in the main, with physical activity.

Nutritional status in children with cancer: Before, during and after therapy.

CONTEXT: Malnutrition is prevalent in children with cancer at diagnosis, especially in low- and middle-income countries (LMIC) where the great majority of children live. It is associated with an added burden of morbidity and mortality. AIMS: Answers were sought to the best measure of nutritional status in LMIC, the impact of anti-neoplastic therapy, effective interventions to achieve normal nutritional status and the impact of these on clinical outcomes. RESULTS: Arm anthropometry offers reasonable estimates of fat mass and lean body mass that are both impacted adversely by treatment. Nutritional supplementation, including the use of simple local resources, is beneficial and can improve survival. Long-term survivors may continue to exhibit perturbed nutritional status. CONCLUSIONS: The prevalence and severity of malnutrition in children with cancer in LMIC demand attention. Opportunities exist to conduct studies in India to examine the effects of nutritional interventions, including on the overall well-being of survivors.

Measurement of socio-economic status in families of children with cancer in Guatemala.

The prospects for survival of children in low and middle income countries are linked to their families socio-economic status (SES), of which income is only one component. Developing a comprehensive measure of SES is required. Informed by clinical experience, a 15-item instrument was designed in Guatemala to categorize SES by five levels in each item. Almost 75% of families attending the Unidad Nacional de Oncología Pediátrica were in the lowest three of six categories, providing a framework for stratified financial and nutritional support. The measure of SES offers an opportunity for examining associations with health outcomes throughout Latin America.

A national study of the provision of oncology sperm banking services among Canadian fertility clinics.

The purpose of this study was to survey the current state of oncology sperm banking services provided by fertility clinics across Canada. A total of 78 Canadian fertility facilities were invited to complete a questionnaire related to the availability, accessibility, affordability and utilisation of sperm banking services for cancer patients. The total response rate was 59%, with 20 (69%) in vitro fertilisation clinics and 26 (53%) other fertility centres returning the survey. A total of 24 responding facilities accepted oncology sperm banking referrals. The time frame to book the first banking appointment for 19 (79%) facilities was within 2 days. Inconsistent practice was found regarding the consent process for cancer patients who are of minority age. Eight (33%) facilities did not provide any subsidy and charged a standard banking fee regardless of patients' financial situations. Overall, the utilisation of oncology sperm banking services was low despite its availability and established efficacy, suggesting that Canadian cancer patients are notably underserved. The study has highlighted some important issues for further consideration in improving access to sperm banking services for cancer patients, especially for adolescents. Better collaboration between oncology and reproductive medicine to target healthcare providers would help to improve sperm banking rates.

Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000).

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20-30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0-18 years were treated on four consecutive protocols: 85-01 (1985-1987), 87-01 (1987-1991), 91-01 (1991-1955) and 95-01 (1996-2000). The 10-year event-free survival (EFS)+/-s.e. by protocol was 77.9+/-2.8% (85-01), 74.2+/-2.3% (87-01), 80.8+/-2.1% (91-01) and 80.5+/-1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

Accounting for body size deviations when reporting bone mineral density variables in children.

UNLABELLED: In a child, bone mineral density (BMD) may differ from an age-expected normal value, not only because of the presence of disease, but also because of deviations of height or weight from population averages. Appropriate adjustment for body size deviations simplifies interpretation of BMD measurements. INTRODUCTION: For children, a bone mineral density (BMD) measurement is normally expressed as a Z score. Interpretation is complicated when weight or height distinctly differ from age-matched children. We develop a procedure to allow for the influence of body size deviations upon measured BMD. METHODS: We examined the relation between body size deviation and spine, hip and whole body BMD deviation in 179 normal children (91 girls). Expressions were developed that allowed derivation of an expected BMD based on age, gender and body size deviation. The difference between measured and expected BMD was expressed as a HAW score (Height-, Age-, Weight-adjusted score). RESULTS: In a second independent sample of 26 normal children (14 girls), measured spine, total femur and whole body BMD all fell within the same single normal range after accounting for age, gender and body size deviations. When traditional Z scores and HAW scores were compared in 154 children, 17.5% showed differences of more than 1 unit and such differences were associated with height and weight deviations. CONCLUSION: For almost 1 in 5 children, body size deviations influence BMD to an extent that could alter clinical management.

Disability and health-related Quality of Life in Long-term Survivors of Cancer in Childhood in Brazil

There is limited experience with patient-reported measurements of health status and health-related quality of life (HRQL) in survivors of cancer in childhood in low-income countries. The purposes of this study were to collect such measurements in Brazil, to test hypotheses about differences among diagnostic groups, and to compare results with those from other countries. Survivors were eligible if diagnosed with cancer in childhood, attending a long-term follow-up clinic, cancer free, literate, and at least 13 years of age. Health status measurements were collected using a Brazilian Portuguese Health Utilities Index questionnaire. Questionnaire responses were converted to scores for morbidity in individual health attributes and for overall HRQL. More than one-third of the 138 consecutive survivors who participated reported some cognitive disability or pain. Approximately one-quarter reported problems with vision, speech, or emotion. Mean HRQL was similar (P>0.05) among countries for survivors of acute lymphoblastic leukemia and Hodgkin disease. The results support the hypotheses that Brazilian survivors of cancer in childhood experience a wide range of disabilities and impaired HRQL, are similar to those in other countries, and should be assessed in long-term follow-up clinics.

Use of paediatric versus adult oncology treatment centres by adolescents 15-19 years old: the Canadian Childhood Cancer Surveillance and Control Program.

The aim of this study was to evaluate the treatment patterns of adolescents with cancer in Canada to ensure this population is receiving the most appropriate care. The Treatment and Outcome Surveillance (TOS) system was compared with the Canadian Cancer Registry (CCR) to estimate the proportion of adolescents (15-19 years) treated in Canadian paediatric oncology centres from 1995 to 2000 inclusive. Using TOS, the demographic, disease, and clinical characteristics of adolescents treated in paediatric versus adult centres in the Prairies were compared and differences were tested statistically. Approximately 30% of Canadian adolescents with cancer were treated in a paediatric centre. Adolescents treated in an adult centre were older at diagnosis and more likely to have carcinoma or germ cell tumours. The time between symptom onset and first treatment was longer for these adolescents, primarily due to the time between first health-care contact and assessment by a treating oncologist or surgeon. They were less likely to be enrolled in a clinical trial. These results suggest that care for adolescents with cancer in Canada is less satisfactory than for younger children, and can be improved.

Alendronate for steroid-induced osteopenia in children with acute lymphoblastic leukaemia or non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND/OBJECTIVES: Osteopenia is a significant morbidity in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL). We conducted a pilot study to assess the impact of alendronate on whole body bone mineral content (WB-BMC), lumbar spine bone mineral density (LS-BMD), biochemical measures of bone mineral metabolism, as well as gross motor function and health-related quality of life (HRQL) in children undergoing therapy for ALL or NHL. METHODS: Ten children (nine boys) between the ages of 3.6 and 14.6 years, on identical maintenance chemotherapy for ALL or NHL were treated with oral alendronate once weekly, and daily calcium supplementation, for a period of six months. Outcome measures were WB-BMC and LS-BMD; biochemical measures of bone mineral metabolism including plasma osteocalcin, C-terminal telopeptide of type I collagen (CTx), serum calcium, 25-hydroxy-vitamin D (25-OHD), and parathyroid hormone (PTH); as well as assessments of motor function and HRQL. RESULTS: A gain in Z score was observed in 7/9 evaluable patients for WB-BMC (mean increase of 0.49) and LS-BMD (0.51). Plasma osteocalcin and CTx showed a change in bone turnover favouring formation over resorption. Serum calcium and 25-OHD remained normal throughout treatment. After an initial spike, serum PTH returned to baseline values at week 4. Measures of motor function showed some improvement and there were modest gains in HRQL. CONCLUSIONS: Alendronate therapy was tolerated well. Further study in a larger sample of children with ALL or NHL is warranted, in the context of a randomized clinical trial.

Health status of young children during therapy for advanced neuroblastoma.

BACKGROUND: The purpose of this study was to describe the health status experienced by young children during various phases of therapy for advanced neuroblastoma. METHODS: Nineteen patients aged 2.00-4.99 years at the time of diagnosis of neuroblastoma (stages 3 or 4) who received active therapy between 1996 and 2000 were enrolled on the study. Their parents provided proxy assessments of their health status at a maximum of 10 assessment points during therapy using the Comprehensive Health Status Classification System for Pre-school Children (CHSCS-PS), which assesses level of function on 10 separate health domains. RESULTS: Eighty-six assessment questionnaires were completed. Maximum morbidity was reported immediately following diagnosis and in the 2-3 weeks following bone marrow transplantation. The greatest morbidity was observed in the pain, self-care, mobility, and emotion domains. CONCLUSIONS: In addition to facing a high risk of mortality, young children being treated for advanced neuroblastoma also experience considerable morbidity.

Inter-observer agreement of a comprehensive health status classification system for pre-school children among patients with Wilms' tumor or advanced neuroblastoma.

We assessed inter-observer agreement on a new comprehensive health status classification system for preschool children (CHSCS-PS). Prospective assessments of children aged 2-4.9 years at the time of diagnosis of neuroblastoma (stages 3-4, excluding 4S) or Wilms' tumor (stages II-V) were collected independently from a parent and nurse by self-report during therapy. Responses were used to determine functional status on 10 health domains, as well as an overall disability score. Inter-observer agreement was evaluated by a kappa statistic for agreement about levels within individual domains, and by an intraclass correlation coefficient (ICC) for agreement of overall disability scores. Twenty-four parent/nurse pairs of assessments were collected. Agreement was almost perfect for mobility and self-care, substantial for emotion and pain, and slight for speech. There was high percent agreement for vision, hearing, dexterity, learning and remembering, and thinking and problem solving, but insufficient variability in responses to calculate a kappa statistic. The ICC for overall disability scores between observers was 0.86, indicating strong agreement. Given the need for, and paucity of, instruments for the measurement of health-related quality of life in very young children, these results strongly support further evaluation of the CHSCS-PS.

The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies.

This paper reviews the Health Utilities Index (HUI) systems as means to describe health status and obtain utility scores reflecting health-related quality of life (HRQoL). The HUI Mark 2 (HUI2) and Mark 3 (HUI3) classification and scoring systems are described. The methods used to estimate multiattribute utility functions for HUI2 and HUI3 are reviewed. The use of HUI in clinical studies for a wide variety of conditions in a large number of countries is illustrated. HUI provides a comprehensive description of the health status of subjects in clinical studies. HUI has been shown to be a reliable, responsive and valid measure in a wide variety of clinical studies. Utility scores provide an overall assessment of the HRQoL of patients. Utility scores are also useful in cost-utility analyses and related studies. General population norm data are available. The widespread use of HUI facilitates the interpretation of results and permits comparisons. HUI is a useful tool for assessing health status and HRQoL in clinical studies.

Health status and health-related quality of life in survivors of cancer in childhood in Latin America: a MISPHO feasibility study.

Cancer is an increasing cause of disease-related death in childhood within developing countries, where the great majority of the world's children reside. The improving prospects for survival in such children, and the corresponding challenge of undertaking economic evaluations of related health interventions, provide a stimulus to study the health-status and health-related quality of life in survivors of cancer in childhood in Latin America. Spanish language versions of questionnaires for proxy assessors, based on the Health Utilities Index (HUI), were used to elicit responses from parents and physicians. The HUI is a family of multi-attribute, generic, preference-linked measures of health status and health-related quality of life that are reliable, responsive and valid, and have been used previously in pediatric oncology. Valid responses were received from 178 parents and 144 physicians in 6 centres in 4 countries (Cuba, Honduras, Colombia and Uruguay). For children with acute lymphoblastic leukemia the major morbidity burdens were in the attributes of emotion, cognition and pain. The overall burden of morbidity was greater in children with non-Hodgkin's lymphoma. In survivors of Hodgkin's disease and Wilms' tumor the attributes most affected were emotion and pain. In general, there was considerable agreement between the assessments provided independently by parents and physicians. This study demonstrates the feasibility of conducting such measurements in developing countries, and reveals similarities in health status and health-related quality of life to comparable populations in more privileged societies.

Magnesium absorption using stable isotope tracers in healthy children and children treated for leukemia.

Intestinal magnesium (Mg) absorption was measured in six healthy children (control) and in four children treated for acute lymphoblastic leukemia with the single-isotope fecal recovery technique (SIFRT). The objective of this study was to determine Mg absorption in young children with acute lymphoblastic leukemia using stable isotope tracers. Fractional and absolute absorption levels determined by SIFRT were not significantly different between children with acute lymphoblastic leukemia (fractional absorption: 58.3 +/- 10.6% [mean +/- SEM], absolute absorption: 3.66 +/- 0.71 mg x kg(-1) x d(-1), [0.15 +/- 0.03 mmol x kg(-1) x d(-1)]) and control children (fractional absorption: 61.4 +/- 7.5%, absolute absorption: 5.69 +/- 0.85 mg x kg(-1) x d(-1), [0.23 +/- 0.03 mmol x kg(-1) x d(-1)]). Average Mg absorption in young children (aged 3--8 y) was 60.2 +/- 5.8%. This study describes the first application of the SIFRT to assess Mg absorption in young children and illustrates the feasibility of the SIFRT in this age group to obtain more accurate information on Mg absorption.

Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity. Compared with prior protocols, post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks. Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR). Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P =.03). There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant prognostic factor (P =.03), with inferior outcomes observed in infants and children 9 years or older. Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P <.01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy.