RESUMO
Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). In total, 77% of survivors with DS reported ≥1 chronic health condition compared with 50% of AML survivors without DS (P=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.
Assuntos
Síndrome de Down/complicações , Leucemia Mieloide Aguda/etiologia , Qualidade de Vida , Sobreviventes , Adolescente , Criança , Pré-Escolar , Doença Crônica/epidemiologia , Síndrome de Down/psicologia , Seguimentos , Indicadores Básicos de Saúde , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Lactente , Leucemia Mieloide Aguda/psicologia , Leucemia Mieloide Aguda/terapia , Sobreviventes/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). PROCEDURE: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. RESULTS: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%. CONCLUSIONS: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Radiação Cranioespinal , Hepatopatia Veno-Oclusiva/epidemiologia , Neoplasias Embrionárias de Células Germinativas/terapia , Adolescente , Neoplasias do Sistema Nervoso Central/mortalidade , Quimiorradioterapia/efeitos adversos , Criança , Pré-Escolar , Radiação Cranioespinal/efeitos adversos , Feminino , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Masculino , Neoplasias Embrionárias de Células Germinativas/mortalidadeRESUMO
BACKGROUND: Therapy for childhood acute myeloid leukemia (AML) has historically included chemotherapy with or without autologous bone marrow transplant (autoBMT) or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to compare health-related quality-of-life (HRQOL) outcomes between these treatment groups. PROCEDURE: Five-year survivors of AML diagnosed before age 21 and enrolled and treated from 1979 to 1995 on one of 4 national protocols were interviewed. These survivors or proxy caregivers completed a health questionnaire and an HRQOL measure. RESULTS: Of 180 survivors, 100 were treated with chemotherapy only, 26 with chemotherapy followed by autoBMT, and 54 with chemotherapy followed by alloBMT. Median age at interview was 20 years (range 8-39). Twenty-one percent reported a severe or life-threatening chronic health condition (chemotherapy-only 16% vs. autoBMT 21% vs. alloBMT 33%; P = 0.02 for chemotherapy-only vs. alloBMT). Nearly all (95%) reported excellent, very good or good health. Reports of cancer-related pain and anxiety did not vary between groups. HRQOL scores among 136 participants ≥14 years of age were similar among groups and to the normative population, though alloBMT survivors had a lower physical mean summary score (49.1 alloBMT vs. 52.2 chemotherapy-only; P = 0.03). Multivariate analyses showed the presence of severe chronic health conditions to be a strong predictor of physical but not mental mean summary scores. CONCLUSIONS: Overall HRQOL scores were similar among treatment groups, although survivors reporting more health conditions or cancer-related pain had diminished HRQOL. Attention to chronic health conditions and management of cancer-related pain may improve QOL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Nível de Saúde , Leucemia Mieloide Aguda/terapia , Qualidade de Vida , Sobreviventes , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Prognóstico , Inquéritos e Questionários , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks. PROCEDURES: Participants were diagnosed with AML at <21 years of age and survived > or =5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo +/- autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS). RESULTS: Of eligible survivors, 117 were > or =18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006). CONCLUSIONS: This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness.
Assuntos
Leucemia Mieloide Aguda/diagnóstico , Sobreviventes , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Fatores de Risco , Inquéritos e Questionários , Transplante Autólogo , Transplante Homólogo , Adulto JovemRESUMO
PURPOSE: This study assessed the relationship between CNS treatment and psychologic mood using the Profile of Moods State (POMS), a standardized measure of affect, among a large sample of young adult survivors of childhood acute lymphoblastic leukemia (ALL; N = 555). PATIENTS AND METHODS: Survivors of childhood ALL (ages 18 to 33 years at study entry) participated in a structured telephone interview eliciting demographic, health, and behavioral data and the POMS. Treatment data included total dose of CNS irradiation (CRT) and intrathecal methotrexate (MTX) obtained from medical records. RESULTS: Mood disturbance was reported by 24% of survivors. High-dose CRT and MTX predicted disturbance rates modestly and primarily in combination with education variables. Interactions between educational achievement, a history of attendance in special education classes, and sex were better predictors than treatment type or dose. Nonwhite males, those younger than 12.5 years of age at diagnosis, and those with negative perceptions of current health and cancer's impact on employment were also at greater risk for mood disturbance (P <.01 to.001). CONCLUSION: Although most survivors are doing well psychologically, a subset of long-term survivors show potentially serious mood disturbance. Mood disturbance seems to be a function of interactions between preexisting individual difference variables (eg, sex, race/ethnicity), treatment factors, and posttreatment educational experiences. Prevention strategies aimed at childhood cancer survivors at greatest risk for mood disturbance may be improved by focus on posttreatment psychosocial and educational supports.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Encefalopatias/terapia , Irradiação Craniana/efeitos adversos , Metotrexato/uso terapêutico , Transtornos do Humor/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Comportamento , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Estresse Psicológico/etiologia , Inquéritos e Questionários , Sobreviventes/psicologia , Resultado do TratamentoRESUMO
PURPOSE: To describe the neurologic and neurosensory deficits in children with brain tumors (BTs), compare incidence of these deficits with that of a sibling control group, and evaluate the factors associated with the development of these deficits. PATIENTS AND METHODS: Detailed questionnaires were completed on 1,607 patients diagnosed between 1970 and 1986 with a primary CNS tumor. Neurosensory and neurologic dysfunctions were assessed and results compared with those of a sibling control group. Medical records on all patients were abstracted, including radiotherapy dose and volume. RESULTS: Seventeen percent of patients developed neurosensory impairment. Relative to the sibling comparison group, patients surviving BTs were at elevated risk for hearing impairments (relative risk [RR], 17.3; P = <.0001), legal blindness in one or both eyes (RR, 14.8; P = <.0001), cataracts (RR, 11.9; P = <.0001), and double vision (RR, 8.8; P = <.0001). Radiation exposure greater than 50 Gy to the posterior fossa was associated with a higher likelihood of developing any hearing impairment. Coordination and motor control problems were reported in 49% and 26%, respectively, of survivors. Children receiving at least 50 Gy to the frontal brain regions had a moderately elevated risk for motor problems (RR, 2.0; P <.05). Seizure disorders were reported in 25% of patients, including 6.5% who had a late first occurrence. Radiation dose of 30 Gy or more to any cortical segment of the brain was associated with a two-fold elevated risk for a late seizure disorder. CONCLUSION: Children surviving BTs are at significant risk for both early and late neurologic or neurosensory sequelae. These sequelae need to be prospectively monitored.
Assuntos
Neoplasias Encefálicas/terapia , Doenças do Sistema Nervoso/etiologia , Sobreviventes , Adulto , Estudos de Casos e Controles , Criança , Epilepsia/etiologia , Feminino , Transtornos da Audição/etiologia , Humanos , Masculino , Distribuição de Poisson , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários , Transtornos da Visão/etiologiaRESUMO
Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.
Assuntos
Neoplasias/psicologia , Neoplasias/reabilitação , Problemas Sociais/prevenção & controle , Problemas Sociais/estatística & dados numéricos , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Causalidade , Criança , Comorbidade , Avaliação Educacional , Escolaridade , Emprego/estatística & dados numéricos , Feminino , Amigos , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Humanos , Deficiências da Aprendizagem/epidemiologia , Deficiências da Aprendizagem/etiologia , Masculino , Casamento/estatística & dados numéricos , Neoplasias/mortalidade , Neoplasias/terapia , Radioterapia/efeitos adversos , Medição de Risco , Ajustamento Social , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS: Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m(2)/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m(2)/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS: The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent. CONCLUSIONS: Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Astrocitoma/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Criança , Pré-Escolar , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Esquema de Medicação , Ependimoma/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Meduloblastoma/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Temozolomida , Resultado do TratamentoRESUMO
BACKGROUND: An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS: Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS: Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for >or=4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (+/-standard deviation) was 14%+/-6% for HGG, 6%+/-6% for MB/PNET and 3%+/-3% for BSG. CONCLUSIONS: Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Glioma/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Quinolonas/uso terapêutico , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Tumores Neuroectodérmicos/tratamento farmacológico , Quinolonas/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: We report results of a phase I trial and pharmacokinetic study of pemetrexed (LY231514) in children and adolescents with refractory solid tumors. Pemetrexed is a novel antifolate that inhibits multiple enzymes necessary for the biosynthesis of thymidine and purine nucleotides. The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic properties of pemetrexed in children. PATIENTS AND METHODS: Pemetrexed was administered as a 10-minute intravenous infusion every 21 days. Patients received vitamin B12 and folic acid supplementation as well as dexamethasone prophylaxis. Cohorts of three to six children were enrolled at dose levels of 400, 520, 670, 870, 1,130, 1,470, 1,910, and 2,480 mg/m2. Pharmacokinetic studies were performed during the first course of treatment. RESULTS: Thirty-three patients (31 assessable) with a median age of 12 years were enrolled. DLT occurred in one of six patients at 1,470 mg/m2 and two of four patients at 2,480 mg/m2. The MTD was 1,910 mg/m2. The primary DLTs were neutropenia and rash. No objective antitumor responses were seen. Mean plasma clearance, half-life, and steady-state volume of distribution values were 2.3 L/h/m2, 2.5 hours, and 5.4 L/m2, respectively. CONCLUSION: Pemetrexed is well-tolerated in children with refractory solid tumors at doses similar to the MTD in adults. The recommended dose for phase II studies is 1,910 mg/m2 administered every 21 days with dexamethasone, folic acid, and vitamin B12 supplementation.
Assuntos
Antagonistas do Ácido Fólico/farmacocinética , Antagonistas do Ácido Fólico/uso terapêutico , Glutamatos/farmacocinética , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Antagonistas do Ácido Fólico/efeitos adversos , Seguimentos , Glutamatos/efeitos adversos , Guanina/efeitos adversos , Guanina/farmacocinética , Guanina/uso terapêutico , Hospitais Pediátricos , Humanos , Imuno-Histoquímica , Lactente , Infusões Intravenosas , Masculino , Dose Máxima Tolerável , Oncologia , Estadiamento de Neoplasias , Neoplasias/mortalidade , Pemetrexede , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE/OBJECTIVES: To determine the feasibility of collecting symptom data at home from school-age children with acute lymphoblastic leukemia (ALL) and from their fathers and mothers and to obtain initial descriptions of pain, sleep disturbance, and fatigue experienced by the family members at home. DESIGN: Prospective and descriptive. SETTING: Children's homes in Oregon and southwestern Washington. SAMPLE: 9 children with ALL (aged 8-16 years), 6 fathers, and 7 mothers. The children received vincristine during the maintenance phase of their outpatient chemotherapy treatments. METHODS: With age-appropriate, paper-and-pencil diaries and wrist actigraphy, data were collected for three days in the families' homes. Families were reminded by telephone to complete their sleep and activity diaries. MAIN RESEARCH VARIABLES: Pain, sleep disturbance, and fatigue in school-age children and their fathers and mothers. FINDINGS: Most of the families who were approached indicated willingness to participate in the study. After receiving outpatient chemotherapy, the children reported pain, sleep disturbance, and fatigue data over three days. Fathers and mothers also reported symptoms. Actigraphy showed children waking more often during the night than mothers or fathers. CONCLUSIONS: Children's pain, sleep disturbance, and fatigue suggest that the symptoms are influencing families' quality of life. Larger studies are needed to examine the symptom patterns and health outcomes of children, fathers, and mothers over the course of chemotherapy. IMPLICATIONS FOR NURSING: Improving sleep and managing pain and fatigue after chemotherapy treatment for children with ALL may improve health outcomes for children and parents.
Assuntos
Saúde da Família , Fadiga/epidemiologia , Dor/epidemiologia , Pais , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Transtornos do Sono-Vigília/epidemiologia , Adolescente , Criança , Fadiga/etiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Dor/etiologia , Projetos Piloto , Estudos Prospectivos , Transtornos do Sono-Vigília/etiologiaRESUMO
BACKGROUND: Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited. METHODS: We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided. RESULTS: A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P<.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%. CONCLUSIONS: The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity.
Assuntos
Antineoplásicos/efeitos adversos , Menopausa Precoce/efeitos dos fármacos , Menopausa Precoce/efeitos da radiação , Neoplasias/terapia , Ovário/efeitos dos fármacos , Ovário/efeitos da radiação , Hipófise/efeitos dos fármacos , Hipófise/efeitos da radiação , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Estudos de Coortes , Feminino , Doença de Hodgkin/terapia , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Razão de Chances , Distribuição de Poisson , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Fatores de Risco , Inquéritos e Questionários , Sobreviventes/estatística & dados numéricosRESUMO
PURPOSE: To assess the safety of delayed high dose intravenous (i.v.) sodium thiosulfate (STS) in a case series of 12 children with malignant brain tumors who were treated with intraarterial (i.a.) carboplatin in conjunction with blood-brain-barrier disruption (BBBD). METHODS: Twelve children ages 17 months-12 years underwent a total of 132 BBBD chemotherapy treatments and also received delayed high dose STS (i.v.). Dose 1 of STS (10-16 g/m(2)) was administered 2 or 4 hr after carboplatin, and a second STS dose was administered 4 hr after dose 1 if the child had impaired baseline hearing. Toxicity data were graded in accordance with the National Cancer Institute Common Toxicity Criteria (Version 2). Audiologic monitoring to evaluate the otoprotective potential of STS was performed on 11 children. Ototoxicity was defined in accordance with the American Speech-Language-Hearing Association (ASHA) criteria. Baseline and end of treatment hearing status were graded using Brock's criteria. RESULTS: Nausea and vomiting were well controlled with anti-emetics administered approximately 30 min prior to STS infusion. Analogous to results in adult patients, there was mild transient hypernatremia and a trend for improved protection from ototoxicity in children who received STS delayed to 4 hr post-treatment versus 2 hr. Tumor responses were seen in heavily pre-treated patients with relatively chemo-resistant tumors, suggesting that STS did not protect the tumor from platinum cytotoxicity. CONCLUSION: High dose STS is well tolerated in children under 12 years of age. Further studies of STS in children are warranted to assess otoprotection and the impact of STS on platinum mediated efficacy.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/efeitos adversos , Quelantes/administração & dosagem , Perda Auditiva Neurossensorial/prevenção & controle , Tiossulfatos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Limiar Auditivo , Barreira Hematoencefálica , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Quelantes/efeitos adversos , Quelantes/farmacocinética , Criança , Pré-Escolar , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ependimoma/tratamento farmacológico , Ependimoma/patologia , Feminino , Perda Auditiva Neurossensorial/induzido quimicamente , Humanos , Lactente , Infusões Intravenosas , Masculino , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/patologia , Análise de Sobrevida , Tiossulfatos/efeitos adversos , Tiossulfatos/farmacocinética , Fatores de TempoRESUMO
BACKGROUND: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies. PATIENTS AND RESULTS: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. CONCLUSIONS: In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.
Assuntos
Transplante de Medula Óssea , Sobrevivência de Enxerto , Trombastenia/terapia , Quimeras de Transplante , Autoanticorpos/sangue , Autoanticorpos/imunologia , Plaquetas/imunologia , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Lactente , Masculino , Agonistas Mieloablativos/administração & dosagem , Agregação Plaquetária , Contagem de Plaquetas/métodos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Trombastenia/sangue , Trombastenia/imunologia , Quimeras de Transplante/sangue , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante/métodosRESUMO
BACKGROUND: Self-concept was compared between adult survivors of childhood acute lymphoblastic leukemia (ALL) and sibling controls. Adult survivor subgroups at greatest risk for negative self-concept were identified. PROCEDURE: Survivors (n = 578) aged > or =18 years, treated before age 20 years on Children's Cancer Group (CCG) ALL protocols, and 396 sibling controls completed a telephone interview and the Harter Adult Self-Perception Profile (ASPP). RESULTS: Survivors global self-worth scores were significantly lower than sibling controls (mean 3.09 vs. 3.18; P = 0.022). Unemployed survivors reported lower global self-worth scores than employed (mean 2.77 vs. 3.12; P = 0.0001), whereas employment status was not associated with self-worth in controls. Among survivors, predictors of negative self-concept included unemployment (odds ratio (OR) = 2.87; 95% CI: 1.50-5.50), and believing that cancer treatment limited employability (OR = 3.17; 95% CI: 1.79-5.62). Unemployment increased the odds for negative self-concept among survivors who received combinations of central nervous system (CNS) irradiation (CRT) and intrathecal methotrexate (IT-MTX), except high CRT with no or low dose IT-MTX. Employed survivors who perceived that treatment limited their employability showed increased odds of negative self-concept for all treatment groups compared to those who did not. Minority ethnic group membership was a borderline significant predictor of negative self-concept (OR = 1.79; 95% CI: 0.94-3.33). CONCLUSIONS: Global self-worth was significantly lower in ALL survivors than sibling controls, however, 81% of survivors had positive self-concept. Survivor subgroups most vulnerable to negative self-concept were the unemployed survivors, believing that cancer treatment affected employability, and ethnic minority group members. Targeted intervention may have greater clinical relevance for these subgroups.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Autoimagem , Sobreviventes/psicologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Terapia Combinada , Coleta de Dados , Emprego , Etnicidade , Seguimentos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Fatores de Risco , IrmãosRESUMO
BACKGROUND: Fertility impairments among women treated during childhood for cancer are known to occur after some, but not all, types of anticancer therapy. Although leukemia is the most common cancer of childhood, until now fertility in survivors has not been comprehensively assessed. PROCEDURE: We investigated functional impairment of fertility in women who were long-term survivors of acute lymphoblastic leukemia (ALL) with a retrospective cohort study. Proven fertility (defined as ever pregnant) was evaluated by self-report among 182 females treated on protocols of the Children's Cancer Group (age at interview, 22.6 years on average) and 170 controls drawn from among the survivors' female siblings (23.4 years). The interview included psychosocial inventories designed to detect mood problems. RESULTS: Significant fertility deficits were noted in female survivors treated with cranial radiotherapy (CRT) at any dose around the time of menarche (relative fertility (RF)) = 0.27, 95% CI = 0.09, 0.82, P = 0.03). Controlling for marital status, mood at interview, and many fertility-related situations did not change the association. CONCLUSION: This study provides evidence for fertility deficits after treatment for ALL with CRT, and, in addition, for the first time, suggests that girls treated around the time of menarche are especially at risk. Clinical confirmation of these results is needed. If gonadal damage occurs in women receiving these treatments, their risk for further sequelae, such as osteoporosis and heart disease, may be significantly raised, requiring active management and intervention.
Assuntos
Fertilidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Adolescente , Adulto , Afeto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Menarca/efeitos da radiação , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group. METHODS: As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS. RESULTS: One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy. CONCLUSIONS: Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy.