RESUMO
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.
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Fungemia/epidemiologia , Fungemia/microbiologia , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/complicações , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/microbiologia , Adolescente , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fungos/classificação , Fungos/isolamento & purificação , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
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Acessibilidade aos Serviços de Saúde/normas , Neoplasias , Bancos de Esperma/estatística & dados numéricos , Adolescente , Adulto , Canadá , Custos de Cuidados de Saúde , Humanos , Consentimento Livre e Esclarecido/normas , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Bancos de Esperma/economia , Bancos de Esperma/provisão & distribuição , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. OBJECTIVES AND METHODS: To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. RESULTS: Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. CONCLUSION: From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.
Assuntos
Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Hemoglobinúria Paroxística/genética , Mutação , Proteínas/genética , Proteínas Ribossômicas/genética , Alelos , Anemia Aplástica , Anemia de Diamond-Blackfan/genética , Doenças da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea , Estudos de Coortes , Insuficiência Pancreática Exócrina/genética , Anemia de Fanconi/genética , Testes Genéticos , Humanos , Lipomatose/genética , Estudos Prospectivos , Síndrome de Shwachman-DiamondRESUMO
Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.
Assuntos
Doenças da Medula Óssea , Insuficiência Pancreática Exócrina , Hemoglobinúria Paroxística , Lipomatose , Alelos , Anemia Aplástica , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/genética , Feminino , Estudos de Associação Genética , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/genética , Humanos , Masculino , Mutação , Síndrome de Shwachman-DiamondRESUMO
The primary objective was to describe predictors of physical, emotional and social quality of life (QoL) in children receiving active treatment for cancer. This Canadian multi-institutional cross-sectional study included children with cancer receiving any type of active treatment. The primary caregiver provided information on child physical, emotional and social QoL according to the PedsQL 4.0 Generic Core scales. Between November 2004 and February 2007, 376 families provided the data. In multiple regression, children with acute lymphoblastic leukemia had better physical health (OR: 0.37, 95% CI 0.23, 0.60; P<0.0001) while intensive chemotherapy treatment (OR: 2.34, 95% CI: 1.42, 3.85; P=0.0008) and having a sibling with a chronic condition (OR: 2.53, 95% CI: 1.54, 4.15; P=0.0002) were associated with poor physical QoL. Better emotional health was associated with good prognosis, less intensive chemotherapy treatment and greater household savings, whereas female children and those with a sibling with a chronic condition had poor social QoL. Physical, emotional and social QoL are influenced by demographic, diagnostic and treatment variables. Sibling and household characteristics are associated with QoL. This information will help to identify children at higher risk of poor QoL during treatment for cancer.
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Neoplasias/psicologia , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Emoções , Feminino , Humanos , Modelos Logísticos , Masculino , Neoplasias/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Análise de RegressãoRESUMO
Familial predisposition to neuroblastoma, a common embryonal cancer of childhood, segregates as an autosomal dominant trait with high penetrance. It is therefore likely that neuroblastoma susceptibility is due to germ line mutations in a tumor suppressor gene. Cytogenetic, functional, and molecular studies have implicated chromosome band 1p36 as the most likely region to contain a suppressor gene involved in sporadic neuroblastoma tumorigenesis. We now demonstrate that neuroblastoma predisposition does not map to any of eight polymorphic markers spanning 1p36 by linkage analysis in three families. In addition, there is no loss of heterozygosity at any of these markers in tumors from affected members of these kindreds. Furthermore, there is strong evidence against linkage to two Hirschsprung disease (a condition that can cosegregate with neuroblastoma) susceptibility genes, RET and EDNRB. We conclude that the neuroblastoma susceptibility gene is distinct from the 1p36 tumor suppressor and the currently identified Hirschsprung disease susceptibility genes.
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Bandeamento Cromossômico , Cromossomos Humanos Par 1 , Neuroblastoma/genética , Adolescente , Criança , Pré-Escolar , Mapeamento Cromossômico , Suscetibilidade a Doenças , Saúde da Família , Feminino , Deleção de Genes , Ligação Genética , Genótipo , Mutação em Linhagem Germinativa , Heterozigoto , Doença de Hirschsprung/genética , Humanos , Lactente , Recém-Nascido , Masculino , LinhagemRESUMO
We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.
Assuntos
Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/genética , Predisposição Genética para Doença , Interleucina-1beta/genética , Leucemia Mieloide Aguda/complicações , Polimorfismo de Nucleotídeo Único , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: Neurodevelopmental evidence of the cerebellum's protracted course of postnatal development suggests that it is particularly sensitive to early toxic insult from cancer therapy. If this is the case, one would expect that there is a relationship between the pattern of neuropsychological and magnetic resonance imaging deficits and that both may indicate cerebellar abnormalities. OBJECTIVE: To investigate the profiles of neuropsychological functions and the morphologic features of the cerebellum, using in vivo magnetic resonance imaging planimetry in survivors of acute lymphoblastic leukemia (ALL) treated with radiation and chemotherapy. DESIGN: Thirteen survivors of childhood ALL with onset at age 2 to 5 years and a uniform protocol of treatment involving cranial radiation of 24 Gy and five doses of intrathecal methotrexate sodium participated in the study. Ten controls matched the patients in age and socioeconomic status. Each child was assessed with a comprehensive battery of neuropsychological tests and with magnetic resonance imaging of the brain. MEASUREMENTS: The neuropsychological scores were transformed into z scores and clustered into right and left hemisphere measures. Planimetric measures of the cerebellar vermis and pons were collected in the midsagittal plane. RESULTS: Consistently observed in survivors of ALL were the following: (1) significant cognitive deficits in visual-spatial-motor coordination and figural memory, functions commonly related to the right side of the brain; and (2) hypoplasia of the cerebellar vermis, lobuli I through V and particularly VI to VII. Lateralization of the neurobehavioral deficits was not reflected in structural brain abnormalities. CONCLUSIONS: Coexistence of the cerebellar hypoplasia and visual-motor coordination and memory deficits supports the neurodevelopmental approach to brain sequelae in survivors of ALL; it also suggests significance of the cerebellum for both motor and complex nonmotor cognitive processing.
Assuntos
Cerebelo/anormalidades , Transtornos Cognitivos/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Cerebelo/patologia , Criança , Transtornos Cognitivos/patologia , Dendritos/patologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
This 2-phase study tested the Family Inventory of Needs-Pediatrics (FIN-PED), a 52-item instrument structured to include 2 subscales, the first measuring the importance of care needs and the second measuring the extent to which needs were met. In Phase I, an expert panel of 6 mothers of children with cancer rated the tool for clarity, apparent internal consistency, and content validity. All items met preset criteria for these assessments. In Phase II, 110 mothers rated the instrument for internal consistency reliability, stability over time, and internal construct validity. Both subscales achieved an estimated internal consistency of 0.94. Evidence of the instrument's stability over time was also achieved. Factor analysis resulted in 4 interpretable factors, suggesting that the tool is multidimensional.
Assuntos
Cuidado da Criança , Mães , Avaliação das Necessidades/organização & administração , Neoplasias/enfermagem , Avaliação em Enfermagem/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Análise Fatorial , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Mães/educação , Mães/psicologia , Pesquisa em Avaliação de Enfermagem , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Fatores de TempoRESUMO
Most patients with acute lymphocytic leukemia (all) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with all do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric all, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and "good" cytogenetics at diagnosis.It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (acgh-"microarray") has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a "molecular karyotype."In the present study, microarray was applied to 9 retrospective cases of pediatric all either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the "molecular karyotype" to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The complementary use of microarray and conventional cytogenetics would allow for more sensitive, comprehensive, and accurate analysis of the underlying genetic profile, with concomitant improvement in prognosis and treatment, not only for pediatric all, but for neoplastic disorders in general.
RESUMO
BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.
Assuntos
Doenças da Medula Óssea/congênito , Sistema de Registros , Adolescente , Adulto , Transfusão de Sangue , Doenças da Medula Óssea/sangue , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , Exame de Medula Óssea , Criança , Pré-Escolar , Aberrações Cromossômicas , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Masculino , SíndromeRESUMO
We describe a young girl with antiphospholipid syndrome (APS) and moyamoya-like cerebrovascular changes which reversed after anticoagulation. Although there was a risk of hemorrhage from collateral vessels, we speculate that this treatment may have prevented progression of the vascular abnormalities, while resolution of the thrombus resulted in improved cerebrovascular circulation.
Assuntos
Síndrome Antifosfolipídica/patologia , Doença de Moyamoya/patologia , Anticorpos Anticardiolipina/sangue , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Angiografia Cerebral , Criança , Feminino , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Varfarina/uso terapêuticoRESUMO
Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
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Ductos Biliares/anormalidades , Transtornos da Coagulação Sanguínea/complicações , Doenças dos Ductos Biliares/sangue , Bilirrubina/sangue , Criança , Pré-Escolar , Humanos , Lactente , Hepatopatias/etiologia , Contagem de Plaquetas , Vitamina E/análise , Vitamina K/uso terapêutico , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/terapiaRESUMO
PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.
Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Indóis/uso terapêutico , Náusea/prevenção & controle , Quinolizinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Administração Oral , Adolescente , Antieméticos/efeitos adversos , Antieméticos/farmacocinética , Criança , Pré-Escolar , Feminino , Humanos , Indóis/efeitos adversos , Indóis/farmacocinética , Masculino , Náusea/induzido quimicamente , Quinolizinas/efeitos adversos , Quinolizinas/farmacocinética , Antagonistas da Serotonina/efeitos adversos , Antagonistas da Serotonina/farmacocinética , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasias Testiculares/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Prednisona/administração & dosagem , Recidiva , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Teniposídeo/administração & dosagem , Neoplasias Testiculares/patologia , Vincristina/administração & dosagemRESUMO
PURPOSE: To describe the clinical and biologic features of neuroblastoma (NB) in two siblings and their maternal second cousin. PATIENTS AND METHODS: NB was diagnosed in the siblings at 2 1/2 (patient 2) and 5 (patient 3) years of age. NB was diagnosed in their maternal second cousin (patient 1) when she was 7 years old. Standard clinical and biological data, tumor karyotype, and tumor allelotype at select loci were obtained. RESULTS: Patient 1 had International Neuroblastoma Staging System (INSS) stage 4 NB and unfavorable histology but no evidence of MYCN amplification; she died from complications of autologous bone marrow transplantation in second remission. Patient 2 had INSS stage 4 NB with unfavorable histology but no MYCN amplification; her disease recurred 39 months after completing therapy. Patient 3 had INSS stage 1 NB with favorable biologic features; he was treated with surgical excision and remains free of disease. CONCLUSIONS: Familial NB may occur at a later age than predicted by the tumor suppressor gene model of inherited cancer. This report further emphasizes the clinical and biological heterogeneity of familial NB.