RESUMEN
BACKGROUND: Health-related quality of life (HRQoL) from diagnosis until end of treatment for children with acute lymphoblastic leukaemia was investigated, examining effects of age, gender, risk-stratified treatment regimen, and therapy intensity (one vs. two 'delayed intensifications' [DIs]). METHOD: In a multi-centre prospective study, parents reported their child's generic and disease-specific HRQoL and their own care-giving burden at five time points. From 1,428 eligible patients, 874 parents completed questionnaires at least once during treatment. RESULTS: At each time point, generic HRQoL was significantly lower than equivalent norm scores for healthy children. HRQoL decreased significantly at the start of treatment, before recovering gradually (but remained below pre-treatment levels). Parents reported that older children worried more about side effects and their appearance, but showed less procedural anxiety than younger children. Concern for appearance was greater among girls than boys. Compared to Regimen B (i.e. additional doxorubicin during induction and additional cyclophosphamide and cytarabine during consolidation chemotherapy), patients receiving Regimen A had fewer problems with pain and nausea. There were no statistically significant differences in HRQoL by number of DI blocks received. INTERPRETATION: HRQoL is compromised at all stages of treatment, and is partly dependent on age. The findings increase understanding of the impact of therapy on children's HRQoL and parental care-giving burden, and will contribute to the design of future trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Calidad de Vida , Adolescente , Adulto , Niño , Preescolar , Quimioterapia de Consolidación , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The overall survival of childhood leukaemia has increased dramatically over recent decades. With the increasing number of survivors, chemotherapy protocols are designed not only to improve cure rates but also to minimise long-term sequelae. Central-nervous-system-directed therapy given as intrathecal chemotherapy and/or cranial irradiation plays a crucial part in acute leukaemia treatment but can also result in adverse effects on the developing brain. The elimination of cranial irradiation from current treatment protocols has improved the neurocognitive outcome without compromising survival rates. Although neurodevelopmental long-term sequelae after chemotherapy-only central-nervous-system-directed therapies may be more subtle, survivors of childhood leukaemia will continue to require methodical follow-up and appropriate rehabilitation.
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Discapacidades del Desarrollo/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Sistema Nervioso Central/patología , Niño , Irradiación Craneana/efectos adversos , Humanos , Infiltración Leucémica/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Traumatismos por Radiación/etiologíaRESUMEN
INTRODUCTION: The availability of health-related quality of life (HRQL) measures that are reliable, valid, brief and comprehensible and appropriate for use with UK children is limited. We report the validation of a HRQL measure suitable for UK use in healthy children, children with chronic disease conditions and socially disadvantaged children. PATIENTS: A total of 1238 children took part in the study, including healthy children as controls (n = 824) and five exemplar groups: children diagnosed with asthma (n = 87), diabetes (n = 103) or inflammatory bowel disease (IBD; n = 69), children in remission from cancer (n = 68) and children in public care (n = 87). METHODS: In phase I, the Manchester-Minneapolis Quality of Life instrument (MMQL) Child Form was translated into UK English. In phases II and III, the questionnaire was shortened and validated. RESULTS: MMQL was anglicised and shortened to five components comprising 29 items. Good internal reliability was found with alpha reaching at least 0.69 for all subscales. Construct validity was established through moderate correlations with comparable PedsQL subscales (Pearson's r ranged from 0.38 to 0.58, p<0.01). Discriminant validity was also demonstrated in children with asthma and IBD, children in remission from cancer and children in public care, all of whom reported significantly lower HRQL than healthy children. Children with diabetes showed similar HRQL to their healthy peers. Good reproducibility and moderate responsiveness were demonstrated for the new measure. CONCLUSIONS: The anglicised and shortened MMQL was shown to be valid and reliable and could be a valuable new tool for the assessment of HRQL in children.
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Asma/psicología , Diabetes Mellitus/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios/normas , Adolescente , Adulto , Asma/epidemiología , Estudios de Casos y Controles , Niño , Diabetes Mellitus/epidemiología , Análisis Factorial , Femenino , Estado de Salud , Humanos , Masculino , Reproducibilidad de los Resultados , Reino Unido/epidemiologíaAsunto(s)
Enfermedades Óseas Metabólicas/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Antimetabolitos Antineoplásicos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Densidad Ósea/efectos de la radiación , Enfermedades Óseas Metabólicas/metabolismo , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/efectos de la radiación , Niño , Preescolar , Femenino , Glucocorticoides/uso terapéutico , Homeostasis/fisiología , Humanos , Masculino , Metotrexato/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMEN
OBJECTIVE: Osteopenia and excess adiposity occur following treatment of childhood acute lymphoblastic leukaemia (ALL) and the use of cranial irradiation is thought to be a significant contributory factor. Hyperleptinaemia has also been demonstrated following cessation of treatment for childhood ALL. Therefore a prospective study was undertaken to evaluate serial changes in percentage bone mineral content (BMC), adiposity and serum leptin concentrations during 2 years of treatment of children with ALL with chemotherapy but without cranial irradiation. DESIGN AND PATIENT: Only patients treated using the MRC ALL 97/ALL 97 (modified 99) protocols for childhood ALL were eligible for entry into the study. A total of 14 patients (seven male, with a median age of 7.5 years (range 3.4-16.7 years) were recruited. Serial dual energy X-ray absorptiometry (DEXA) scanning was undertaken at diagnosis and during two years of treatment. Serum leptin concentrations were determined at the same time as the scans. RESULTS: Reductions in %BMC were observed at the hip and lumbar spine by 12 months (P < 0.01) and remained low after 24 months of treatment. Subanalysis of %BMC measurements at the hip demonstrated a greater reduction in %BMC at the trochanteric region compared to the femoral neck. The percentage corrected fat mass increased from 6 months whereas the body mass index (BMI) standard deviation score (SDS) was increased after 24 months of treatment (P < 0.05). Serum leptin concentrations increased following 24 months of therapy (P < 0.05). CONCLUSIONS: Children treated for ALL with contemporary regimens have a predisposition to osteopenia, excess adiposity and hyperleptinaemia during treatment without cranial irradiation administration. We speculate that in addition to glucocorticoid administration, leptin resistance may account in part for these observations.
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Enfermedades Óseas Metabólicas/complicaciones , Leptina/sangre , Obesidad/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Obesidad/metabolismo , Obesidad/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Estudios ProspectivosRESUMEN
Studies in children treated with chemotherapy suggest that chemotherapeutic agents have deleterious effects on bone metabolism. We therefore evaluated the in vitro effects of clinically relevant concentrations of chemotherapeutic agents on the synthesis of type I collagen, alkaline phosphatase (AP) activity, and mineralization by primary human osteoblast-like (HOB) cells derived from children. Because serum 1,25-dihydroxyvitamin D(3) concentrations may be reduced during treatment with chemotherapy, the effect of chemotherapeutic agents on HOB cells cultured in the presence or absence of 1,25-dihydroxyvitamin D(3) was also evaluated. Type I collagen synthesis was reduced by all agents (P < 0.01) other than methotrexate, whereas the relative AP activity was increased (P < 0.01) by all agents. The relative number of cells staining intensely for AP after culture with agents increased (P < 0.05), and AP mRNA expression was increased (P < 0.01) with vincristine. 1,25-Dihydroxyvitamin D(3) ameliorated (P < 0.01) the depletion of HOB cell numbers by chemotherapeutic agents. Furthermore, vincristine and daunorubicin inhibited 1,25-dihydroxyvitamin D(3)-mediated AP activity (P < 0.01). We conclude that chemotherapeutic agents can adversely affect HOB cell function, and we speculate that this observation may account, in part, for the osteopenia observed during and after treatment of children with chemotherapy.
Asunto(s)
Antineoplásicos/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Adolescente , Fosfatasa Alcalina/antagonistas & inhibidores , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Calcitriol/farmacología , Recuento de Células , Células Cultivadas , Niño , Preescolar , Colágeno Tipo I/biosíntesis , Sinergismo Farmacológico , Femenino , Humanos , Masculino , Minerales/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , ARN Mensajero/metabolismoRESUMEN
Clinical studies suggest that combination chemotherapy adversely affects bone metabolism and in vitro studies have demonstrated that a reduction in osteoblast numbers results in diminished bone formation. The aim of this study was to investigate the in vitro effects of combinations of chemotherapeutic agents on primary human osteoblast-like (hOB) cell numbers and apoptosis, and to assess the ability of hOBs and osteoprogenitor (HCC1) cells to recover from prior treatment with chemotherapy. As glucocorticoids are frequently administered during treatment with cytotoxic agents, we evaluated whether glucocorticoids influence the chemosensitivity of hOB and human osteosarcoma (MG63) cells. Culture with clinically relevant concentrations of the individual chemotherapeutic agents reduced hOB cell numbers compared with control (p < 0.01) and also increased the numbers of apoptotic cells (p < 0.05). Potentiation of cytotoxicity was observed when agents were given in combination, thus further reducing cell numbers, and this effect was greatest when vincristine was given in combination with asparaginase. Following culture with a chemotherapeutic agent, there was greater recovery of hOB compared with HCC1 cell numbers (p < 0.01). Pretreatment with glucocorticoids ameliorated the adverse effects of chemotherapeutic agents on hOB and MG63 cell numbers and apoptosis (p < 0.05). We conclude that the use of combination chemotherapy contributes to osteopenia in childhood malignancy by a reduction in osteoblast numbers. However, this effect may be attenuated by the concomitant use of glucocorticoids.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Osteoblastos/efectos de los fármacos , Adolescente , Apoptosis/efectos de los fármacos , Enfermedades Óseas Metabólicas/patología , Niño , Daunorrubicina/farmacología , Etopósido/farmacología , Femenino , Glucocorticoides/farmacología , Neoplasias Hematológicas/inducido químicamente , Neoplasias Hematológicas/prevención & control , Humanos , Osteoblastos/patología , Células Madre/efectos de los fármacos , Células Madre/patología , Células Tumorales Cultivadas , Vincristina/farmacologíaRESUMEN
Osteopenia is a complicating problem that may occur during and after treatment for childhood malignancy. Clinical studies suggest that chemotherapeutic agents directly affect osteoblasts in vivo. Since combinations of agents are used for treatment, we individually investigated the chemosensitivity of human osteoblast-like cells to 11 of the chemotherapeutic agents used. The relative chemosensitivity of osteoblast-like cells representing different stages of cell differentiation was also examined. Cell numbers were evaluated following culture of an established human osteoblast-like cell line (MG63) for 3 days with clinically relevant concentrations of the chemotherapeutic agents. The chemosensitivity of MG63 cells was compared to that of a human osteoprogenitor cell line (HCC1) and primary osteoblast-like (HOB) cells derived from pediatric bone. Cell numbers were reduced by all agents in all cell types, although there was a varied response between agents at equimolar concentrations. In MG63 cells the lowest concentration of agent significantly reducing cell numbers varied between agents, for example, methotrexate (10(-7) M), vincristine (10(-9) M), and etoposide (10(-7) M) (all P <0.01). The less differentiated osteoblast phenotypes were significantly more chemosensitive at equimolar concentrations of methotrexate, vincristine, asparaginase, and dexamethasone than more differentiated phenotypes (all P <0.01). Furthermore, four agents significantly increased alkaline phosphatase (AP) activity in HOB cells. We conclude that individual chemotherapeutic agents added to osteoblast cell cultures reduce cell numbers, with osteoblast precursor cells being preferentially depleted. These results suggest that most of the agents may contribute to osteopenia in childhood malignancy by direct effects on cell numbers.
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Enfermedades Óseas Metabólicas/tratamiento farmacológico , Osteoblastos/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Asparaginasa/metabolismo , Asparaginasa/farmacología , Recuento de Células/métodos , Técnicas de Cultivo de Célula , Diferenciación Celular , Dexametasona/metabolismo , Dexametasona/farmacología , Etopósido/metabolismo , Etopósido/farmacología , Humanos , Metotrexato/metabolismo , Metotrexato/farmacología , Osteoblastos/citología , Osteoblastos/metabolismo , Vincristina/metabolismo , Vincristina/farmacologíaAsunto(s)
Neoplasias/terapia , Calidad de Vida , Sobrevivientes , Adaptación Psicológica , Factores de Edad , Antineoplásicos/efectos adversos , Niño , Empleo , Sistema Endocrino/efectos de la radiación , Cardiopatías/inducido químicamente , Humanos , Infertilidad/etiología , Relaciones Interpersonales , Esperanza de Vida , Trastornos Mentales/etiología , Neoplasias/psicología , Osteoporosis/inducido químicamente , Pubertad , Radioterapia/efectos adversos , Factores de Riesgo , Sobrevivientes/psicologíaAsunto(s)
Neoplasias/terapia , Sobrevivientes , Enfermedades Cardiovasculares/inducido químicamente , Medicina Basada en la Evidencia , Medicina Familiar y Comunitaria , Estudios de Seguimiento , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Enfermeras Practicantes , Estudios RetrospectivosRESUMEN
The relationship between child- and parent-reported quality of life (QOL) and the effects of parental mental health, illness stressors, and child vulnerability was explored using two measures of QOL: the Pediatric Cancer Quality Life-32 (Varni et al., 1998a) and the Disquol (Eiser, Cotter, Oades, Seamark, & Smith, 1999). Thirty-two children with acute lymphoblastic leukaemia (mean age = 8.92 years) and 36 parents completed measures of QOL when attending routine clinic. In addition, parents also completed the General Health Questionnaire (GHQ-28), perception of the child's vulnerability, and illness-related stressors. Significant correlations were found between the overall scores on the two child-completed QOL measures, with a range of poor, moderate to good correlations found between the individual subscales. Poor to moderate concordance was found between child and parent reports. Children who self-reported poorer QOL had mothers who were more depressed. Parents who reported poorer QOL for their child reported more illness stressors and perceived their child as being more vulnerable. Assumptions that concordance between child and parent ratings of QOL is a necessary requirement for new measures of QOL are challenged.
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Salud Mental , Padres/psicología , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicología , Calidad de Vida/psicología , Estrés Psicológico , Adulto , Niño , Depresión/psicología , Femenino , Humanos , Masculino , Proyectos de Investigación , Autoevaluación (Psicología)RESUMEN
Primary lung tumours in childhood are rare. However, cancer in a child may have an impact on the lung in a number of ways. Chemotherapy and radiotherapy may be directly toxic to the lung. Young children are particularly sensitive to the effects of radiotherapy, which can cause impairment of growth of muscle, skin and bone, in addition to its direct toxic effect on the underlying lung. The lung is vulnerable to infection - particularly protozoal, viral and fungal organisms, as well as bacterial. Children undergoing bone marrow transplantation are at greater risk of lung damage, as they are profoundly immunosuppressed and have received intensive cytotoxic chemotherapy or radiotherapy. The underlying cause of lung damage may be difficult to determine because of the complexity of treatment and the additional risk of infectious complications. In a small number of children, pulmonary complications may be fatal. However, for the many survivors, although abnormalities of lung function are frequently detected, these are rarely clinically significant and, with notable exceptions, do not appear to deteriorate with time. However, data remain scanty; there is a real need for ongoing prospective studies of lung function in survivors of childhood cancer.
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Enfermedades Pulmonares/etiología , Neoplasias/complicaciones , Antineoplásicos/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Niño , Humanos , Neoplasias Pulmonares/patología , Radioterapia/efectos adversos , Infecciones del Sistema Respiratorio/etiologíaRESUMEN
We report a case of juxtaposed Wilms' tumor (WT) and cystic nephroma (CN) in a 21-month-old girl which gave rise to radiological diagnostic difficulty. Preoperative chemotherapy was given, resulting in marked tumor necrosis but the cystic nephroma remained untouched. Histological examination showed characteristic features of a triphasic WT and a CN; the two lesions were separated by a thick fibrous capsule. While everybody agrees that WT and cystic partially differentiated nephroblastoma (CPDN) are closely related, there are two opposite views about their relationship to CN. One is that CN may represent the final step in maturation of WT and CPDN. Other authors argue that there is no evidence to support this theory but believe CN might have something in common with nephrogenic rests. We suggest that the two lesions in the present case may have originated from two intralobar nephrogenic rests, which would strengthen the latter view.
Asunto(s)
Neoplasias Renales/patología , Enfermedades Renales Poliquísticas/patología , Tumor de Wilms/patología , Femenino , Humanos , Lactante , Tomografía Computarizada por Rayos XAsunto(s)
Neumonía por Pneumocystis/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Antiinfecciosos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tos/etiología , Diagnóstico Diferencial , Femenino , Fiebre/etiología , Humanos , Lactante , Cooperación del Paciente , Neumonía por Pneumocystis/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
There are now more than one million new cases of cancer every year in the European Community (EC) including the children to whom particular needs should be addressed. Besides the disease-free survival other outcomes reflecting the impact of treatment on the patient and their families must also be assessed and include their physical, psychological and social functioning throughout their care: during therapy, after completion of treatment or, for some, in the terminal phase of their illness. To provide optimal care and thus improve the quality of life for these children needs: a) an appropriately structured Paediatric Cancer Unit; b) well trained and permanent staff members: comprising doctors, nurses, psychologists, social workers and other health care professionals; c) facilities such as a specific out-patient clinic, a hospital school, a residence for parents; d) a well defined programme for the terminally ill children; e) a well defined programme for controlling the late effects of therapy.
Asunto(s)
Neoplasias/psicología , Calidad de Vida , Adolescente , Niño , Preescolar , Europa (Continente) , Humanos , Italia , Neoplasias/terapia , Atención al Paciente , Educación del Paciente como Asunto , Sobrevivientes/psicología , Cuidado TerminalAsunto(s)
Infertilidad Femenina/etiología , Infertilidad Masculina/etiología , Neoplasias/terapia , Medicina Reproductiva , Antineoplásicos/efectos adversos , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Embarazo , Complicaciones del Embarazo/etiología , Radioterapia/efectos adversos , Sobrevivientes , Enfermedades Uterinas/etiologíaAsunto(s)
Calidad de Vida , Adolescente , Niño , Supervivencia sin Enfermedad , Humanos , Neoplasias/complicaciones , Neoplasias/psicologíaRESUMEN
Four children with spinal cord compression due to malignant tumours are presented. The severity of the condition was not initially recognized by parents, or the nature of the likely cause by the initial physicians. Lower limb asymmetrical weakness, clear-cut sensory levels, and marked pain indicate need for urgent imaging and exclusion of a space occupying lesion. In 1997 diagnosis of Guillain-Barré syndrome should not be made without careful prior spinal imaging.