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2.
Hum Reprod ; 34(6): 1083-1094, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31116405

RESUMO

STUDY QUESTION: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER: NCT02184806.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Criopreservação , Preservação da Fertilidade/métodos , Neoplasias/tratamento farmacológico , Ovário/transplante , Adolescente , Adulto , Autoenxertos/efeitos dos fármacos , Autoenxertos/fisiologia , Autoenxertos/transplante , Coeficiente de Natalidade , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Sobrevivência de Enxerto , Humanos , Nascido Vivo , Menstruação/fisiologia , Ovário/efeitos dos fármacos , Ovário/fisiologia , Gravidez , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores de Tempo , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
3.
Clin Genet ; 94(2): 252-258, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29700810

RESUMO

Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. However, the specific phenotype and natural history remain to be defined. We correlate molecular data, phenotype, and clinical history of 5 unreported affected children and all individuals reported in the literature. All patients present features consistent with IBMFS: bone marrow failure, growth retardation, failure to thrive, developmental delay, recurrent infections, and skin, teeth or hair abnormalities. Additional features present in some individuals include retinal abnormalities, pancreatic insufficiency, liver cirrhosis, skeletal abnormalities, congenital hip dysplasia, joint hypermobility, and cryptorchidism. We suggest that DNAJC21-related diseases constitute a distinct IBMFS, with features overlapping Shwachman-Diamond syndrome and Dyskeratosis congenita, and additional characteristics that are specific to DNAJC21 mutations. The full phenotypic spectrum, natural history, and optimal management will require more reports. Considering the aplastic anemia, the possible increased risk for leukemia, and the multisystemic features, we provide a checklist for clinical evaluation at diagnosis and regular follow-up.


Assuntos
Anormalidades Múltiplas/genética , Anemia Aplástica/genética , Doenças da Medula Óssea/genética , Instabilidade Genômica/genética , Proteínas de Choque Térmico HSP40/genética , Hemoglobinúria Paroxística/genética , Anormalidades Múltiplas/fisiopatologia , Anemia Aplástica/diagnóstico , Anemia Aplástica/patologia , Anemia Aplástica/fisiopatologia , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/fisiopatologia , Transtornos da Insuficiência da Medula Óssea , Pré-Escolar , Disceratose Congênita/genética , Disceratose Congênita/fisiopatologia , Insuficiência Pancreática Exócrina/genética , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Efeito Fundador , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/fisiopatologia , Humanos , Lactente , Lipomatose/genética , Lipomatose/fisiopatologia , Masculino , Mutação , Fenótipo , Ribossomos/genética , Síndrome de Shwachman-Diamond , Telômero/genética
4.
Nature ; 463(7279): 344-8, 2010 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-20090751

RESUMO

In the lowermost layer of the atmosphere-the troposphere-ozone is an important source of the hydroxyl radical, an oxidant that breaks down most pollutants and some greenhouse gases. High concentrations of tropospheric ozone are toxic, however, and have a detrimental effect on human health and ecosystem productivity. Moreover, tropospheric ozone itself acts as an effective greenhouse gas. Much of the present tropospheric ozone burden is a consequence of anthropogenic emissions of ozone precursors resulting in widespread increases in ozone concentrations since the late 1800s. At present, east Asia has the fastest-growing ozone precursor emissions. Much of the springtime east Asian pollution is exported eastwards towards western North America. Despite evidence that the exported Asian pollution produces ozone, no previous study has found a significant increase in free tropospheric ozone concentrations above the western USA since measurements began in the late 1970s. Here we compile springtime ozone measurements from many different platforms across western North America. We show a strong increase in springtime ozone mixing ratios during 1995-2008 and we have some additional evidence that a similar rate of increase in ozone mixing ratio has occurred since 1984. We find that the rate of increase in ozone mixing ratio is greatest when measurements are more heavily influenced by direct transport from Asia. Our result agrees with previous modelling studies, which indicate that global ozone concentrations should be increasing during the early part of the twenty-first century as a result of increasing precursor emissions, especially at northern mid-latitudes, with western North America being particularly sensitive to rising Asian emissions. We suggest that the observed increase in springtime background ozone mixing ratio may hinder the USA's compliance with its ozone air quality standard.


Assuntos
Atmosfera/química , Ozônio/análise , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Ásia , Ecossistema , Efeito Estufa , História do Século XX , História do Século XXI , América do Norte , Ozônio/síntese química , Ozônio/química , Tamanho da Amostra , Estações do Ano
5.
BMC Palliat Care ; 15: 33, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27000049

RESUMO

Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.


Assuntos
Cuidados Paliativos , Qualidade de Vida , Humanos , Neoplasias/tratamento farmacológico
6.
Pediatr Hematol Oncol ; 33(7-8): 423-437, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27960645

RESUMO

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , França , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Taxa de Sobrevida
7.
Curr Oncol ; 23(6): e598-e604, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28050150

RESUMO

BACKGROUND: Since the early 2000s, treatment options for multiple myeloma have rapidly expanded, adding significant complexity to the management of this disease. To our knowledge, no systematic qualitative research on clinical decision-making in multiple myeloma has been published. We sought to characterize how physicians view and implement guidelines and incorporate novel approaches into patient care. METHODS: We designed a semi-structured qualitative interview guide informed by literature review and an expert advisory panel. We conducted 60-minute interviews with a diverse sample of oncology physicians in the southeast United States. We used a constant comparative method to code and analyze interview transcripts. The research team and advisory panel discussed and validated emergent themes. RESULTS: Participants were 13 oncologists representing 5 academic and 4 community practices. Academic physicians reported using formal risk-stratification schemas; community physicians typically did not. Physicians also described differences in eligibility criteria for transplantation; community physicians emphasized distance, social support, and psychosocial capacity in making decisions about transplantation referral; the academic physicians reported using more specific clinical criteria. All physicians reported using a maintenance strategy both for post-transplant and for transplant-ineligible patients; however, determining the timing of maintenance therapy initiation and the response were reported as challenging, as was recognition or definition of relapse, especially in terms of when treatment re-initiation is indicated. CONCLUSIONS: Practices reported by both academic and community physicians suggest opportunities for interventions to improve patient care and outcomes through optimal multiple myeloma management and therapy selection. Community physicians in particular might benefit from targeted education interventions about risk stratification, transplant eligibility, and novel therapies.

8.
Ann Oncol ; 29(5): 1091-1092, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-32138850
9.
Ann Oncol ; 29(5): 1090-1091, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788171
11.
J Adv Model Earth Syst ; 14(6): e2021MS002852, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35864944

RESUMO

The NASA Goddard Earth Observing System (GEOS) Composition Forecast (GEOS-CF) provides recent estimates and 5-day forecasts of atmospheric composition to the public in near-real time. To do this, the GEOS Earth system model is coupled with the GEOS-Chem tropospheric-stratospheric unified chemistry extension (UCX) to represent composition from the surface to the top of the GEOS atmosphere (0.01 hPa). The GEOS-CF system is described, including updates made to the GEOS-Chem UCX mechanism within GEOS-CF for improved representation of stratospheric chemistry. Comparisons are made against balloon, lidar, and satellite observations for stratospheric composition, including measurements of ozone (O3) and important nitrogen and chlorine species related to stratospheric O3 recovery. The GEOS-CF nudges the stratospheric O3 toward the GEOS Forward Processing (GEOS FP) assimilated O3 product; as a result the stratospheric O3 in the GEOS-CF historical estimate agrees well with observations. During abnormal dynamical and chemical environments such as the 2020 polar vortexes, the GEOS-CF O3 forecasts are more realistic than GEOS FP O3 forecasts because of the inclusion of the complex GEOS-Chem UCX stratospheric chemistry. Overall, the spatial patterns of the GEOS-CF simulated concentrations of stratospheric composition agree well with satellite observations. However, there are notable biases-such as low NO x and HNO3 in the polar regions and generally low HCl throughout the stratosphere-and future improvements to the chemistry mechanism and emissions are discussed. GEOS-CF is a new tool for the research community and instrument teams observing trace gases in the stratosphere and troposphere, providing near-real-time three-dimensional gridded information on atmospheric composition.

12.
Infect Dis Now ; 51(4): 357-361, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33096202

RESUMO

BACKGROUND: Microbiological tests are required for individuals on HIV Pre-Exposure Prophylaxis (PrEP), but their real-life numbers, types and cost are poorly described. METHODS: Number, type, and results of microbiological tests performed in a Besançon Hospital-associated laboratory, France, from 2016 to 2019, in the setting of PrEP consultations were retrospectively collected. Costs were estimated by the current reimbursement rate set by the French national protection system. RESULTS: 756 consultations for PrEP initiation or follow-up of 135 persons were performed over 4 years. Among 3434 tests performed in the institution-associated laboratory, 1083 and 2351 were virological and bacteriological tests, respectively. Serology was predominant in virology (98% of virological tests), with HIV, HCV, and HBV screening as the 3 more frequent assays, whereas molecular biology was predominant in bacteriology (63.1% of bacteriological tests) with N. gonorrhoeae and C. trachomatis screening as leader assays. Agar-based culture accounted for 1% of bacterial tests. The global cost of microbiological tests was 45,983.20 euros, corresponding to a mean cost of 60.80 euros per consultation. Virological and bacteriological tests accounted for 37.7% and 62.3% of this budget, respectively. No seroconversion was observed for HIV or HCV. N. gonorrhoeae and C. trachomatis were detected at least once in 39.3% and 22.4% of individuals, respectively, with 15% of symptomatic episodes in both cases. Active syphilis infection was detected in 15.4% of individuals. CONCLUSIONS: Since numerous microbiological tests are required during PrEP, the availability of specific technical platforms should not be neglected by centers wishing to set up PrEP consultations.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Técnicas Microbiológicas/economia , Técnicas Microbiológicas/estatística & dados numéricos , Profilaxia Pré-Exposição/métodos , Adulto , Técnicas Bacteriológicas/economia , Técnicas Bacteriológicas/estatística & dados numéricos , Chlamydia trachomatis/isolamento & purificação , Feminino , França , Hospitais , Humanos , Masculino , Neisseria gonorrhoeae/isolamento & purificação , Estudos Retrospectivos , Comportamento Sexual , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/virologia , Virologia/economia , Virologia/métodos
13.
Hemasphere ; 3(6): e316, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31976488

RESUMO

The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, p < 0.0001 and 26% vs 12%, p = 0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (p < 0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (p = 0.83). Five-year EFS was 67% for infants vs 58% for older children (p = 0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.

14.
Leukemia ; 21(2): 238-47, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17170721

RESUMO

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Encefalopatias Metabólicas/induzido quimicamente , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Fatores Etários , Encefalopatias Metabólicas/epidemiologia , Encefalopatias Metabólicas/prevenção & controle , Criança , Pré-Escolar , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Neurotoxinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Medição de Risco
15.
Arch Pediatr ; 15(9): 1464-73, 2008 Sep.
Artigo em Francês | MEDLINE | ID: mdl-18556182

RESUMO

Hereditary spherocytosis (HS) is the commonest inherited disorder of the erythrocyte membrane in Northern Europe and North America. It is marked by a regenerative anemia which varies widely from asymptomatic patients to severe hemolysis. In 75% of HS patients, inheritance is autosomal dominant. The diagnosis of HS is easily made when there are a family history, hemolytic anemia, reticulocytosis, spherocytes and increased hyperdense cells. Specialized testing to clarify the nature of membrane disorder is required when the film appearance is atypical without a positive family history, in the absence of a family history, in the newborn and before the splenectomy, to rule out the stomatocytosis which is contraindicated. The indication for splenectomy is dependent on the degree of anemia and its clinical manifestation.


Assuntos
Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/terapia , Criança , Colecistectomia , Membrana Eritrocítica/fisiologia , Transfusão de Eritrócitos , Eritropoetina , Humanos , Proteínas Recombinantes , Esferocitose Hereditária/genética , Esplenectomia
16.
Bone Marrow Transplant ; 40(3): 219-24, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17530002

RESUMO

We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.


Assuntos
Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Adolescente , Doenças Ósseas/etiologia , Doenças Ósseas/mortalidade , Doenças Ósseas/psicologia , Catarata/etiologia , Catarata/mortalidade , Catarata/psicologia , Criança , Pré-Escolar , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Transtornos da Alimentação e da Ingestão de Alimentos/mortalidade , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/psicologia , Humanos , Hipotireoidismo/etiologia , Hipotireoidismo/mortalidade , Hipotireoidismo/psicologia , Incidência , Lactente , Infecções , Artropatias/etiologia , Artropatias/mortalidade , Artropatias/psicologia , Pneumopatias/etiologia , Pneumopatias/mortalidade , Pneumopatias/psicologia , Masculino , Segunda Neoplasia Primária , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Irradiação Corporal Total
17.
Leukemia ; 20(2): 187-92, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16341042

RESUMO

A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon alpha-based regimen. In all, 30 children from eight European countries were enrolled. In 18 children assessable for hematologic response, imatinib mesylate induced complete hematologic response in eight (80%) of the 10 patients included in chronic phase and in six (75%) of eight enrolled in advanced phase of the disease with acceptable toxicity. In 27 patients assessable for cytogenetic response, imatinib mesylate induced disappearance of Philadelphia chromosome-positive bone marrow cells in 12 (60%) of 20 children included in chronic phase and in two (29%) of seven included in advanced phase. A reduction of the bcr-abl/abl ratio to less than 10(-4) was achieved in 11 (50%) of the children included in chronic phase. Estimated 12-month overall survival rate was 95% (95% CI, 87-100%) for the patients included in chronic phase and 75% (95%CI, 45-100%) for those enrolled in advanced phase. Imatinib mesylate is well tolerated and molecular remission can be achieved in children with CML.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transplante de Células-Tronco , Adolescente , Benzamidas , Criança , Pré-Escolar , Doença Crônica , Esquema de Medicação , Europa (Continente) , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Lactente , Masculino , Recidiva , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
18.
Leukemia ; 20(6): 965-70, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16598313

RESUMO

In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFalpha/beta genes impairs normal hematopoietic differentiation and is supposed to cooperate with additional mutations promoting proliferation. The incidence and the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001). RTK mutations were associated with a higher white blood cell count (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002 and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras mutations did not affect prognosis. Screening for RTK mutations may help to identify patients with a more adverse outcome and thus susceptible to benefit from intensified protocols or RTK inhibitors.


Assuntos
Fatores de Ligação ao Core/genética , Leucemia Mieloide/genética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Tirosina Quinase 3 Semelhante a fms/genética , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Éxons , Feminino , Humanos , Lactente , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Leukemia ; 19(8): 1338-44, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15973457

RESUMO

The t(6;9)(p23;q34) is a recurrent chromosomal abnormality observed in 1% of acute myelogenous leukemia (AML), which generates a fusion transcript between DEK and CAN/NUP214 genes. We used a DEK-CAN real-time quantitative (RQ)-PCR strategy to analyze 79 retrospective and prospective samples from 12 patients. Five patients reached DEK-CAN negativity (sensitivity 10(-5)); all underwent early allogeneic hematopoietic stem cell transplantation (median 5.5 months from diagnosis) with some demonstrating molecular positivity at the time of allograft. All four cases in CCR with adequate follow-up (median 18.5 months, range 13--95) demonstrate persistent molecular negativity, whereas all seven patients with persistent DEK-CAN positivity died at a median of 12 months from diagnosis (range 7--27). We conclude that DEK-CAN molecular monitoring by RQ-PCR in t(6;9) malignancies is a useful tool for individual patient management and that molecular negativity is indispensable for survival, but should not be a prerequisite for allografting in this rare, poor prognosis, subset of AML.


Assuntos
Leucemia Mieloide/diagnóstico , Técnicas de Diagnóstico Molecular , Proteínas Oncogênicas/análise , Proteínas Recombinantes de Fusão/análise , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide/mortalidade , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase , Prognóstico , Proteínas Recombinantes de Fusão/genética , Taxa de Sobrevida
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