RESUMO
BACKGROUND: Patients with high-risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal function. PROCEDURE: Long-term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.9 years) HR NBL survivors by plasma creatinine (P-Cr), urea, and cystatin C (P-Cys C) concentrations, urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Ambulatory blood pressure was monitored, and common carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) were evaluated. RESULTS: No significant difference in P-Cr, P-Cys C, or eGFR was found between the NBL survivors and the age- and sex-matched 20 controls. P-Cys C-based eGFR (eGFRcysc) was significantly lower than the P-Cr-based eGFRcr (97 ± 17 mL/min/1.73 m2 vs 111 ± 19 mL/min/1.73 m2 , P < 0.001) among the NBL survivors. The eGFRcysc was below normal in 28%, and ACR was above normal in 22% of the NBL survivors. Abnormal blood pressure was found in 56% of the survivors, and an additional 17% were normotensive at daytime but had significant nocturnal hypertension. Both ACR and P-Cys C were associated with nighttime diastolic hypertension. CONCLUSIONS: Long-term survivors of childhood HR NBL showed signs of only mild renal dysfunction associated with diastolic hypertension. Elevated ACR and P-Cys C were the most sensitive indicators of glomerular renal dysfunction and hypertension in this patient cohort.
Assuntos
Sobreviventes de Câncer , Hipertensão , Testes de Função Renal , Neuroblastoma , Adolescente , Adulto , Creatinina/sangue , Cistatina C/sangue , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Masculino , Neuroblastoma/sangue , Neuroblastoma/terapia , Ureia/sangueRESUMO
AIM: Children with refractory or high-risk malignancies frequently suffer from poor quality of life during palliative care. This study explored the effect of metronomic drug administration on survival and quality of life in paediatric patients with various refractory or high-risk tumours. METHODS: We treated 17 patients with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression-free survival, changes in the Karnofsky-Lansky scores from baseline to the end of the study therapy and radiological responses. RESULTS: The median overall survival after the start of the study therapy was 6.2 months (range 2.0-57.7), and the six-, 12- and 24-month survival rates were 59%, 18% and 18%, respectively. The median progression-free survival was 3.2 months (range 0.3-17.8). The Karnofsky-Lansky scores increased significantly during the study therapy (p = 0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III-V adverse events occurred in 76% of the patients. CONCLUSION: Metronomic therapy may increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events.
Assuntos
Neoplasias/tratamento farmacológico , Cuidados Paliativos , Seleção de Pacientes , Qualidade de Vida , Administração Metronômica , Criança , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Neoplasias/mortalidade , Estudos ProspectivosRESUMO
Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P<0.001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0±10.6%), which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva , Medição de Risco , Taxa de SobrevidaRESUMO
High-dose therapy (HDTx) with autologous stem cell rescue has been widely applied in very-poor-risk pediatric solid tumors. Promising data have become available with the use of high-dose busulfan, whereas high-dose (HD) thiotepa is less commonly used. We report retrospectively our single-institution experience from 1986 to 2012 of single and tandem HDTx with special emphasis on HD-thiotepa as the backbone of HD regimen in Ewing family tumors, including all 24 patients in the Helsinki University Hospital referral area in population-based fashion (Ewing sarcoma 9, Askin tumor 9, peripheral neuroectodermal tumor 6). The 10-year overall survival for the entire cohort was 0.73±0.01. Thirteen out of the 24 underwent HDTx (10 single, 3 tandem). The HDTx regimen consisted of HD-thiotepa (900 mg/m), VP16, and carboplatin. Additional HD-melphalan and total body irradiation were used in the tandem regimens. There was no toxic mortality. The 5-year event-free survival was 0.73±0.16 for high-risk cases transplanted in 1CR. In the relapse group, 1 out of the 3 survived. Radiotherapy to axial sites was given safely in combination with HD-thiotepa in all 3 patients. Thiotepa-based HDTx approach resulted in an encouraging outcome without toxic mortality for high-risk patients. HD-thiotepa merits further studies in larger controlled series.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/terapia , Sarcoma de Ewing/terapia , Tiotepa/administração & dosagem , Adolescente , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Ósseas/mortalidade , Quimiorradioterapia , Criança , Pré-Escolar , Terapia Combinada , Quimioterapia de Consolidação/métodos , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Procedimentos Ortopédicos , Sarcoma de Ewing/mortalidadeRESUMO
BACKGROUND: The aim of the study was to evaluate arterial morphology and function in a national cohort of long-term survivors of high-risk neuroblastoma (NBL) treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation with or without total body irradiation (TBI). METHODS AND RESULTS: Common carotid, femoral, brachial, and radial artery morphology were assessed with very-high-resolution vascular ultrasound (25-55 MHz), and carotid artery stiffness and brachial artery flow-mediated dilatation measured with conventional vascular ultrasound in 19 adult or pubertal (age 22.7 ± 4.9 years, range 16-30) NBL survivors transplanted during 1984-1999 at the mean age of 2.5 ± 1.0 years. Results were compared with 20 age- and sex-matched healthy controls. The cardiovascular risk assessment included history, body mass index, fasting plasma lipids, glucose, and 24-h ambulatory blood pressure (BP). The survivors had consistently smaller arterial lumens, increased carotid intima-media thickness (IMT), plaque formation (N = 3), and stiffness, as well as increased radial artery intima thickness (N = 5) compared with the control group. Survivors displayed higher plasma triglyceride and cholesterol levels, and increased heart rate, as well as increased systolic and diastolic BPs. TBI (N = 10) and a low body surface area were independent predictors for decreased arterial lumen size and increased IMT. Three out of five survivors with subclinical intima thickening had arterial plaques. Plaques occurred only among TBI-treated survivors. CONCLUSIONS: Long-term childhood cancer survivors treated with TBI during early childhood display significant signs of premature arterial aging during young adulthood.
Assuntos
Espessura Intima-Media Carotídea , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/etiologia , Túnica Íntima/diagnóstico por imagem , Irradiação Corporal Total/efeitos adversos , Adolescente , Adulto , Autoenxertos , Glicemia/metabolismo , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Jejum/sangue , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lipídeos/sangue , Masculino , Neuroblastoma/terapia , Placa Aterosclerótica/sangue , Sobreviventes , Rigidez VascularRESUMO
BACKGROUND: Increasing evidence suggests that early and rapid lymphocyte recovery following allogeneic hematopoietic stem cell transplantation (HSCT) is associated with better survival. PROCEDURE: We retrospectively analyzed very early lymphocyte subset counts following transplantation from our 5-year pediatric allogeneic HSCT material to find clinically relevant associations with post transplant outcome, and the major complication of HSCT, acute graft-versus-host disease (aGVHD). We analyzed HSCTs performed due to acute leukemias and lymphomas from matched unrelated donors (MUD, n = 33), unrelated cord blood (UCB, n = 9) and matched sibling donors (MSD, n = 17). RESULTS: Patients with grafts from MUDs and grade II-IV aGVHD) had higher (median 2.1 compared to 0.3, P<0.0001) and earlier (at day +18 post transplant vs. day +25, P = 0.004) first measurable CD4(+) /CD8(+) T cell ratio, compared to patients with no or grade I aGVHD, respectively. At day +32 after HSCT patients with MUDs and significant aGVHD had higher levels of both CD4(+) and CD8(+) T cell subsets. Low (below median 120/µL) versus high natural killer (NK) cell counts at day +32 were associated with 3-year event-free survival of 27.4 +/- 9.0% versus 82.4 +/- 6.4% (P < 0.0001), cumulative transplant-related mortality of 44.7 +/- 12.2% versus 3.0 +/- 3.0% (P < 0.001) and cumulative relapse incidence of 50.4 +/- 12.2% versus 15.0 +/- 6.2% (P = 0.019), respectively. CONCLUSIONS: We conclude that early lymphocyte subset counts following allogeneic HSCT have an association with aGVHD and post transplant outcome.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/imunologia , Doença Aguda , Aloenxertos , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/patologia , Humanos , Lactente , Leucemia/sangue , Leucemia/imunologia , Leucemia/mortalidade , Leucemia/patologia , Leucemia/terapia , Linfoma/sangue , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/terapia , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: Both osteoporosis and cardiovascular disease (CVD) are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low physical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD) and turnover markers (BTMs) in apparently healthy cohort. DESIGN: A cross-sectional assessment of 155 healthy 32-year-old adults (74 males) was performed for skeletal status, CVD risk factors and lifestyle factors. METHODS: We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP), collagen I carboxy-terminal telopeptide (ICTP) and urine collagen I aminoterminal telopeptide (U-NTX), as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were assessed using DXA scanning. Associations were tested with partial correlations in crude and adjusted models. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria) with multivariate analysis. RESULTS: Osteocalcin and P1NP correlated inversely with insulin (Râ=â-0.243, Pâ=â0.003 and Râ=â-0.187, Pâ=â0.021) and glucose (Râ=â-0.213, Pâ=â0.009 and Râ=â-0.190, Pâ=â0.019), but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (Râ=â-0.162, Pâ=â0.053 and Râ=â-0.093, Pâ=â0.266) and with glucose (Râ=â-0.099, Pâ=â0.240 and Râ=â-0.133, Pâ=â0.110), respectively. Whole body BMD associated inversely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model. CONCLUSIONS: In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass, no association continued to be present. In addition to fat mass, lifestyle factors, especially physical activity, modified the associations between CVD and bone characteristics. Prospective studies are needed to specify the role of mediators and lifestyle factors in the prevention of CVD and osteoporosis.
Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/fisiologia , Doenças Cardiovasculares/etiologia , Adulto , Biomarcadores/sangue , Osso e Ossos/diagnóstico por imagem , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Estilo de Vida , Masculino , Estudos Prospectivos , Radiografia , Fatores de RiscoRESUMO
BACKGROUND: High-dose methotrexate (HD-MTX) is potentially nephrotoxic. The feasibility of novel biomarkers to indicate renal injury due to HD-MTX infusion was studied in children with acute lymphoblastic leukemia (ALL). PROCEDURE: Markers for glomerular and tubular injury were evaluated prospectively after HD-MTX infusion in 20 children with ALL. Plasma creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured 24-48 hr before MTX-infusion and 24, 36, 48, and 72 hr after starting the HD-MTX treatment, and thereafter daily until the MTX concentration was below 0.1 µmol/L. Urine NGAL, ß2 -microglobulin, and creatinine concentrations as well as dipstick and urinalysis were performed at the same time points. RESULTS: In children with ALL, HD-MTX treatment at 5 g/m(2) over 24 hr was well tolerated and none of the patients developed significant glomerular or tubular dysfunction. The mean plasma cystatin C level increased significantly (P < 0.001) from 0.83 mg/L at baseline to 0.94 mg/L at 36 hr after starting the HD-MTX treatment. The cystatin C concentration remained within reference range in all but two patients (10%). There was no significant change in plasma creatinine level during or after HD-MTX treatment, the values being normal in all patients. Plasma and urea NGAL did not increase during or after the HD-MTX treatment. CONCLUSIONS: Our results suggest that plasma cystatin C concentration alone is a sensitive marker to monitor renal function during and after HD-MTX infusion in pediatric ALL patients. Plasma or urine NGAL do not provide any further advantage in the follow-up of these patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores/análise , Cistatina C/sangue , Metotrexato/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Proteínas de Fase Aguda/urina , Adolescente , Criança , Pré-Escolar , Creatinina/urina , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Testes de Função Renal , Lipocalina-2 , Lipocalinas/urina , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas/urina , Microglobulina beta-2/urinaRESUMO
We evaluated the role of mismatched third-party hematopoietic stem cells (TPC) in shortening the neutropenia after umbilical cord blood transplantation (UCBT). A TPC graft was given to 7/37 children with UCBT to support engraftment due to anticipated increased risk of nonengraftment (N=6) or active infection (N=1). TPC grafts were collected with apheresis from haploidentical family members. The median UCB and CD34 cell counts were 5.10 (range, 4.13 to 9.98)×10/kg and 5.98 (range, 4.40 to 14.00)×10/kg, respectively. The median time to neutrophil engraftment was shorter in the patients with TPC (12 d; range, 9 to 24 d) than those without (23 d; range, 12 to 44 d) (P=0.010). TPC chimerism was lost in median at 28 (range, 24 to 103) days posttransplant. TPC grafts from mothers engrafted similarly as the grafts from other family members. UCB graft cell count and the use of methotrexate posttransplant strongly contributed to engraftment. TPC may form a valuable transient bridging graft over the neutropenia after UCBT in patients with anticipated high-risk of nonengraftment or toxicity due to pretransplant infections.
Assuntos
Sangue Fetal/transplante , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Adolescente , Adulto , Plaquetas/citologia , Criança , Pré-Escolar , Feminino , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Humanos , Lactente , Masculino , Neutrófilos/citologia , Neutrófilos/transplante , Estudos Retrospectivos , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Testicular dysfunction and infertility are of major concern in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). This study assesses predictive factors for very long-term testicular recovery after allogeneic HSCT in childhood and adolescence. PROCEDURE: Testicular volume, sperm production and long-term need of testosterone substitution were evaluated among 106 male survivors transplanted at Huddinge and Helsinki University Hospitals from 1978 through 2000, at a mean age of 8 ± 4.6 years (range 1-17). A mean ± SD of 13 ± 4.8 years (range 4-28) had elapsed since their HSCT and the mean age of the participants was 22 ± 6.0 years (range 12-42). An adult testicular volume was recorded in 74 patients at a mean age of 19 ± 3.3 years (range 14-36). RESULTS: Recipients conditioned with busulfan-based regimens or regimens containing only cyclophosphamide had significantly larger adult testicular volumes (mean volume 18 ml and 16 ml vs. 9 ml, P < 0.00001, respectively) and lower serum levels of FSH (mean 9 IU and 5 IU vs. 19 IU, P < 0.01 and 0.001, respectively) compared to those conditioned with total body irradiation (TBI). Multivariate analysis demonstrated that a non-leukemia diagnosis (P < 0.01) and adult testicular volume ≥ 15 ml (P < 0.03) positively impacted spermatogenetic recovery. CONCLUSIONS: A larger adult testicular volume, normal serum levels of FSH and spermatozoa detected in a majority of seminal fluids after busulfan-based or cyclophosphamide conditionings suggest very long-term recovery of spermatogenesis after chemotherapy-based regimens. A simple measurement of adult testicular volume may help predict spermatogenetic potential among pediatric HSCT survivors.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Infertilidade Masculina/etiologia , Neoplasias/complicações , Espermatogênese , Sobreviventes , Testículo/patologia , Adolescente , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Irradiação Craniana/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Hormônio Foliculoestimulante/sangue , Terapia de Reposição Hormonal , Humanos , Lactente , Infertilidade Masculina/sangue , Infertilidade Masculina/patologia , Infertilidade Masculina/prevenção & controle , Masculino , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia , Tamanho do Órgão , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Puberdade , Lesões por Radiação/sangue , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Análise do Sêmen , Testículo/efeitos dos fármacos , Testículo/efeitos da radiação , Testosterona/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversosRESUMO
BACKGROUND: Despite major treatment attempts, the prognosis for pediatric diffuse intrinsic pontine gliomas (DIPGs) remains dismal. Gliomas are highly vascularized tumors, suggesting that the prevention of vessel formation by anti-angiogenic treatment might be effective. PROCEDURE: Forty-one pediatric patients with DIPG were treated according to the Angiocomb protocol, starting with radiotherapy combined with topotecan and followed by anti-angiogenic triple medication consisting of thalidomide, etoposide, and celecoxib. Overall survival, radiological response, quality of life, requirement of corticosteroids, and adverse effects were monitored. Eight patients treated with only radiotherapy were used as controls. RESULTS: For study patients, the 12 and 24 months overall survival was 61% and 17%, respectively. The median overall survival was 12 months (range 4-60 months). Four radiological complete responses were seen, of which two were transient. Radiologically, 56% of the tumors reduced in size and 78% in signal intensity. Study patients were able to visit school or daycare and walk for a significantly longer time compared to controls (Log Rank 0.036 and 0.008, respectively). Adverse effects were generally minor. CONCLUSIONS: The Angiocomb protocol created a noticeable share of long-term survivors and was well tolerated, suggesting that anti-angiogenic therapy for patients with DIPG should be studied more in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Tronco Encefálico/terapia , Quimiorradioterapia , Glioma/terapia , Qualidade de Vida , Adolescente , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Estudos de Casos e Controles , Celecoxib , Quimioterapia Adjuvante , Criança , Pré-Escolar , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Lactente , Masculino , Gradação de Tumores , Prognóstico , Pirazóis/administração & dosagem , Indução de Remissão , Sulfonamidas/administração & dosagem , Taxa de Sobrevida , Talidomida/administração & dosagem , Topotecan/administração & dosagemRESUMO
The aim of the present study was to evaluate the impact of infant breast-feeding on cardiovascular risk in young adults. This unique study group involved 158 subjects (eighty-two females) originally collected prospectively at birth in 1975 and followed up to the age of 32 years. Frequent visits during the first year guaranteed the knowledge of the precise duration of breast-feeding. All infants received at least some breast milk. Participants were assessed for both individual cardiovascular risk factors (blood pressure, plasma lipids, homeostatic model assessment of insulin resistance and waist circumference) and the general clinical risk of cardiovascular events by calculating the Framingham risk score (FRS) and the metabolic syndrome criteria score (NCEP-ATPIII; National Cholesterol Education Program's Adult Treatment Panel III). Data on lifestyle factors were carefully collected. Linear regression analyses revealed that the effect of the duration of breast-feeding was not relevant (0·02 decrease in the FRS per one additional breast-feeding month; 95 % CI - 0·19, 0·09). Similarly, the effect of breast-feeding was minor on all of the individual cardiovascular risk factors. We used sex, physical activity, dietary fat and vitamin C, smoking and alcohol consumption as covariates. Again, logistic regression analyses detected no significant impact of the duration of breast-feeding on the risk of the metabolic syndrome according to the NCEP-ATPIII (OR 0·95, 95 % CI 0·8, 1·1). The strongest independent predictor for later CVD risk was male sex. In conclusion, in this prospectively followed cohort of young adults born at term and at weight appropriate for gestational age, the duration of breast-feeding did not have an impact on the accumulation of cardiovascular risk factors.
Assuntos
Aleitamento Materno , Doenças Cardiovasculares , Consumo de Bebidas Alcoólicas , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Gorduras na Dieta/administração & dosagem , Exercício Físico , Feminino , Seguimentos , Humanos , Recém-Nascido , Resistência à Insulina , Lipídeos/sangue , Masculino , Síndrome Metabólica , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fumar , Fatores de Tempo , Circunferência da CinturaRESUMO
Children with acute lymphoblastic leukemia (ALL) have several risk factors for deep venous thromboses (DVTs) such as central venous catheters and asparaginase (ASP), related antithrombin (AT) deficiency. After introduction of a new standard and intermediate-risk ALL treatment protocol with prolonged continuous ASP treatment, two symptomatic DVTs in 10 patients were observed at the Children's Hospital, Helsinki, Finland. To prevent further thrombotic complications yet ensuring continuous exposure to ASP, an AT substitution strategy was adopted in Helsinki. The same ALL treatment protocol is used without AT substitution in the other Nordic countries. In this retrospective study, we describe the effect of prolonged ASP treatment on AT and fibrinogen levels in children without AT substitution in Stockholm, Sweden (n = 39) and the AT substitution in children with AT activity below 0.55 kIU/l in Helsinki (n = 36, intervention group). The intervention group is compared with children treated similarly earlier in Helsinki without AT substitution (n = 10). The median lowest AT activity during the ASP treatment without AT substitution was 0.55 kIU/l. Fibrinogen level of 1.0 g/l or less was found in 14% of all routine samples during the ASP treatment. In the intervention group, 23 (64%) received AT concentrate. Two (20%) children had symptomatic DVT before initiation of the AT substitution and two (6%) thereafter. We conclude that most children are exposed to low AT activity during ASP treatment predisposing to thrombosis. The effect of prophylactic AT substitution remains unclear.
Assuntos
Deficiência de Antitrombina III/induzido quimicamente , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Deficiência de Antitrombina III/sangue , Deficiência de Antitrombina III/diagnóstico , Criança , Pré-Escolar , Feminino , Fibrinogênio/metabolismo , Humanos , Lactente , Masculino , Fatores de RiscoRESUMO
Children with high-risk neuroblastoma (NBL) constitute a heterogenous group, but little attention has been paid to further subdivision of the high-risk group. Although the current therapies including multiple high-dose consolidations have neared their efficacy and tolerability limits, alternative therapies are needed. We wanted to define an ultrahigh-risk group among high-risk NBL patients, to be potential candidates for novel therapies given up-front. Children with high-risk NBL (n=59) treated at a single institution during 1987 to 2010 were evaluated for upfront prognostic factors at diagnosis and response to induction therapy. The overall outcome was not different during 1987 to 1994 versus 1995 to 2010. Therapy consisted of induction chemotherapy, surgery, and high dose-consolidation (single, tandem, or triple) with autologous stem cell rescue, followed by local irradiation and cis-retinoic acid. MYCN amplification and bone metastases were powerful upfront prognostic factors, and a combination of these determined an ultrahigh-risk group with a 5-year event-free survival of 0.125±0.083. The combination of MYCN amplification and bone metastases overruled the intensity of the therapy given and remained the only significant predictor (P<0.019) in a multiple step-wise forward Cox regression analysis. We conclude that high-risk NBL patients can be categorized into prognostic subgroups based on MYCN status and bone metastases. MYCN amplification and bone metastases combined determined an ultrahigh-risk group of patients being suitable candidates for novel alternative therapies.
Assuntos
Neuroblastoma/classificação , Neuroblastoma/genética , Neuroblastoma/patologia , Adolescente , Neoplasias Ósseas/secundário , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Proteína Proto-Oncogênica N-Myc , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Prognóstico , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparison with array comparative genomic hybridization (aCGH), and besides, to detect novel genetic anomalies. We found a high concordance of copy number variations (CNVs) as detected by next generation sequencing (NGS) and aCGH. By both methodologies, the recurrent deletion at CDKN2A/B locus was identified, whereas NGS revealed additional, small regions of CNVs, seen more frequently in adult patients, while aCGH was better at detecting larger CNVs. Also, by NGS, we detected novel structural variations, novel SNVs and small insertion/deletion variants. Our results show that NGS, in addition to detecting mutations and other genetic aberrations, can be used to study CNVs.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 9/genética , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Feminino , Genes p16 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
BACKGROUND: BK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads. OBJECTIVES: Characterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment. STUDY DESIGN: By prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments). RESULTS: Decreasing BKV viremia of>2log(10)copies/mL and clinical resolution was seen in 4 patients over 5-12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patients CONCLUSIONS: The data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.
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Vírus BK/isolamento & purificação , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Cistite/epidemiologia , Cistite/virologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/transmissão , Administração Intravenosa , Administração Intravesical , Antivirais/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Cidofovir , Infecção Hospitalar/tratamento farmacológico , Cistite/tratamento farmacológico , Cistite/patologia , Citosina/administração & dosagem , Citosina/análogos & derivados , Feminino , Hemorragia/epidemiologia , Hemorragia/patologia , Hemorragia/virologia , Humanos , Masculino , Organofosfonatos/administração & dosagem , Plasma/virologia , Infecções por Polyomavirus/tratamento farmacológico , Transplante , Resultado do Tratamento , Urina/virologia , Carga ViralRESUMO
BACKGROUND: Ewing's sarcoma family of tumors (ESFTs) are rare bone and soft tissue tumors characterized by specific genetic alterations. Our aim was to carry out a nationwide analysis of ESFT, to survey the treatments used and to report the five-year disease specific and event-free survival rates (EFS and DSS). MATERIAL AND METHODS: The study data was gathered from the Finnish National Cancer Registry and all five University Hospitals and consisted of 76 bone and soft tissue ESFT patients diagnosed during 1990-2009. Their medical records were reviewed and data on their disease, treatments, complications and outcome were analyzed. RESULTS: The five-year EFS and DSS of patients with localized disease at diagnosis (n = 57) were 70% and 60%, respectively. Factors contributing to DSS and EFS were the axial vs. peripheral site of primary tumor and adequate surgical resection of the primary tumor. DSS was also affected by patient's age at diagnosis and the treatment employed. The five-year DSS of patients with metastatic disease at diagnosis (n = 19) was 33% and both preoperative and high dose chemotherapy were associated with improved survival. CONCLUSION: Population-based studies including both bone and soft tissue ESFTs are few. In this nationwide, population-based study on Finnish bone and soft tissue ESFT patients, we find their treatment successful and results comparable to those previously published. Absence of metastases, young age at diagnosis and a peripheral primary tumor site were associated with a better prognosis. It seems that surgical resection of the primary tumor should be performed whenever adequate resection margins can be achieved. The role of high dose chemotherapy merits further studies in this setting.
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Neoplasias Ósseas/epidemiologia , Sarcoma de Ewing/epidemiologia , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Terapia Combinada , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Metástase Neoplásica , Sistema de Registros/estatística & dados numéricos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Sarcoma de Ewing/terapia , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The impact of breastfeeding on adult body composition is controversial. We evaluated effects of lifestyle and childhood-related factors, including infant feeding, on adult body composition. METHODS: We determined total body and trunk fat and lean mass by densitometry in 158 adults who were born full-term and prospectively followed from birth to the age of 32 years. Data on various factors, extending from infancy to adulthood, with potential effect on body composition, were recorded. RESULTS: Scapular skinfold thickness at 12 months correlated with adult trunk (R = 0.22, p = 0.005) and body fat percentage (R = 0.18, p = 0.023). In linear regression analysis, current physical activity (R = -0.33, p < 0.001) and maternal BMI (R = 0.28, p = 0.002) were associated with adult body fat percentage. Gender (R = 0.78, p < 0.001) and weight gain during infancy (R = 0.147, p = 0.008) were associated with adult lean mass. In the analysis of covariance, prolonged breastfeeding tended to lead to lower fat percentage in adulthood, but no direct association with the duration of breastfeeding and adult body composition was confirmed. CONCLUSIONS: Current physical activity, growth in infancy, gender and maternal BMI influence adult body composition. Breastfeeding has an indirect influence on adult body fat accumulation by affecting growth and body adiposity in infancy.
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Composição Corporal , Índice de Massa Corporal , Aleitamento Materno , Absorciometria de Fóton , Tecido Adiposo/anatomia & histologia , Adulto , Antropometria , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosAssuntos
Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Outcome of high risk neuroblastoma (NBL) remains unsatisfactory in spite of intensive treatment efforts. Consolidation with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) has been intensified with tandem and triple cycles with promising results. Our purpose was to improve the outcome with two or three HD-consolidations. METHODS: Thirty six children with high risk NBL, diagnosed 1995-2010, had intensive induction and surgery, and were stratified to single, tandem or triple HD-therapy and ASCT, followed by local irradiation and cis-retinoic acid. In inoperable patients surgery was facilitated by preoperative HD-melphalan. Long-term outcome of our old cohort from 1987-1994 was updated. RESULTS: Ten year event-free survival (EFS) from diagnosis was 0.44+/-0.10 of the old and 0.43+/-0.085 of the new cohort. EFS from the last ASCT was 0.53 +/-0.12 and 0.48+/-0.091, respectively. Preoperative HD-melphalan rendered 73% of bulky primaries operable in the new cohort. The 5-yr EFS from ASCT was 0.46+/-0.15 for single and 0.73+/-0.15 for tandem ASCT (P = 0.19). All triple ASCT patients, selected by poor/slow response, relapsed or died. CONCLUSIONS: Thiotepa- and melphalan based HD regimens, with or without total body irradiation (TBI), appeared to give an outcome comparable to major NBL study groups with acceptable toxicity. Tandem HD therapy gave a 5-year EFS of 73%, whereas a third HD consolidation did not offer any additional advantage for ultra high risk patients with slow response. Pediatr Blood Cancer 2012; 59: 1190-1197. © 2012 Wiley Periodicals, Inc.