Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
J Med Screen ; : 9691413241232899, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509806

RESUMO

OBJECTIVE: Many population-based breast screening programmes temporarily suspended routine screening following the COVID-19 pandemic onset. This study aimed to describe screening mammography utilisation and the pattern of screen-detected breast cancer diagnoses following COVID-19-related screening disruptions in Ireland. METHODS: Using anonymous aggregate data from women invited for routine screening, three time periods were examined: (1) January-December 2019, (2) January-December 2020, and (3) January-December 2021. Descriptive statistics were conducted and comparisons between groups were performed using chi-square tests. RESULTS: In 2020, screening mammography capacity fell by 67.1% compared to 2019; recovering to 75% of mammograms performed in 2019, during 2021. Compared to 2019, for screen-detected invasive breast cancers, a reduction in Grade 1 (14.2% vs. 17.2%) and Grade 2 tumours (53.4% vs. 58.0%) and an increase in Grade 3 tumours (32.4% vs. 24.8%) was observed in 2020 (p = 0.03); whereas an increase in Grade 2 tumours (63.3% vs. 58.0%) and a reduction in Grade 3 tumours (19.6% vs. 24.8%) was found in 2021 (p = 0.02). No changes in oestrogen receptor-positive or nodal-positive diagnoses were observed; however the proportion of oestrogen/progesterone receptor-positive breast cancers significantly increased in 2020 (76.2%; p < 0.01) and 2021 (78.7%; p < 0.001) compared to 2019 (67.8%). CONCLUSION: These findings demonstrate signs of a grade change for screen-detected invasive breast cancers early in the pandemic, with recovery evident in 2021, and without an increase in nodal positivity. Future studies are needed to determine the COVID-19 impact on long-term breast cancer outcomes including mortality.

2.
Childs Nerv Syst ; 40(3): 791-800, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37955716

RESUMO

PURPOSE: To describe a surgical technique for posterior cerebral revascularization in pediatric patients with moyamoya arteriopathy. Here, we describe the clinical characteristics, surgical indications, operative techniques, and clinical and radiographic outcomes in a series of pediatric patients with moyamoya disease affecting the posterior cerebral artery (PCA) territory. METHODS: A retrospective single-center series of all pediatric patients with moyamoya disease who presented to our institute between July 2009 through August 2019 were reviewed. The clinical characteristics, surgical indications, operative techniques, and long-term clinical and radiographic outcomes of pediatric moyamoya patients with PCA territory ischemia were collected and analyzed. RESULTS: A total of 10 PCA revascularization procedures were performed in 9 patients, 5 female, ages 1 to 11.1 years (average 5.2 years). Complications included 1 stroke, with no infections, hemorrhages, seizures, or deaths. One patient had less than 1 year of radiographic and clinical follow-up. In 8 of 9 patients with at least 1 year of radiographic follow-up, there was engraftment of surgical vessels present in all cases. No new strokes were identified on long-term follow-up despite the radiographic progression of the disease. In the 8 cases available for analysis, the average follow-up was 50.8 months with a range of 12 to 117 months. CONCLUSIONS: PCA territory ischemia in patients with progressive moyamoya disease can be surgically treated with indirect revascularization. Here, we describe our experience with PCA revascularization procedures for moyamoya disease, including pial pericranial dural (PiPeD) revascularization and pial synangiosis utilizing the occipital artery. These surgical options may be useful for decreasing the risk of stroke in pediatric moyamoya patients with severe posterior circulation disease.


Assuntos
Isquemia Encefálica , Revascularização Cerebral , Doença de Moyamoya , Acidente Vascular Cerebral , Criança , Humanos , Feminino , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Angiografia Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Infarto Cerebral/etiologia , Acidente Vascular Cerebral/etiologia , Revascularização Cerebral/métodos
3.
Cell Mol Neurobiol ; 44(1): 12, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38150042

RESUMO

Intracranial vascular malformations manifest on a continuum ranging from predominantly arterial to predominantly venous in pathology. Cerebral cavernous malformations (CCMs) are capillary malformations that exist at the midpoint of this continuum. The axon guidance factor Ephrin B2 and its receptor EphB4 are critical regulators of vasculogenesis in the developing central nervous system. Ephrin B2/EphB4 dysregulation has been implicated in the pathogenesis of arterial-derived arteriovenous malformations and vein-based vein of Galen malformations. Increasing evidence supports the hypothesis that aberrant Ephrin B2/EphB4 signaling may contribute to developing vascular malformations, but their role in CCMs remains largely uncharacterized. Evidence of Ephrin dysregulation in CCMs would be important to establish a common link in the pathogenic spectrum of EphrinB2/Ephb4 dysregulation. By studying patient-derived primary CCM endothelial cells (CCMECs), we established that CCMECs are functionally distinct from healthy endothelial cell controls; CCMECs demonstrated altered patterns of migration, motility, and impaired tube formation. In addition to the altered phenotype, the CCMECs also displayed an increased ratio of EphrinB2/EphB4 compared to the healthy endothelial control cells. Furthermore, whole exome sequencing identified mutations in both EphrinB2 and EphB4 in the CCMECs. These findings identify functional alterations in the EphrinB2/EphB4 ratio as a feature linking pathophysiology across the spectrum of arterial, capillary, and venous structural malformations in the central nervous system while revealing a putative therapeutic target.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Receptor EphB2 , Receptor EphB4 , Humanos , Receptor EphB4/genética , Receptor EphB2/genética , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Células Endoteliais/patologia , Cultura Primária de Células , Sequenciamento do Exoma , Masculino , Feminino , Pré-Escolar , Criança , Adolescente
4.
Eur J Radiol Open ; 11: 100510, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37560166

RESUMO

Introduction: High mammographic breast density (MBD) is an independent breast cancer risk factor. In organised breast screening settings, discussions are ongoing regarding the optimal clinical role of MBD to help guide screening decisions. The aim of this scoping review was to provide an overview of current practices incorporating MBD within population-based breast screening programmes and from professional organisations internationally. Methods: This scoping review was conducted in accordance with the framework proposed by the Joanna Briggs Institute. The electronic databases, MEDLINE (PubMed), EMBASE, CINAHL Plus, Scopus, and Web of Science were systematically searched. Grey literature sources, websites of international breast screening programmes, and relevant government organisations were searched to identify further relevant literature. Data from identified materials were extracted and presented as a narrative summary. Results: The search identified 78 relevant documents. Documents were identified for breast screening programmes in 18 countries relating to screening intervals for women with dense breasts, MBD measurement, reporting, notification, and guiding supplemental screening. Documents were identified from 18 international professional organisations with the majority of material relating to supplemental screening guidance for women with dense breasts. Key factors collated during the data extraction process as relevant considerations for MBD practices included the evidence base needed to inform decision-making processes and resources (healthcare system costs, radiology equipment, and workforce planning). Conclusions: This scoping review summarises current practices and guidelines incorporating MBD in international population-based breast screening settings and highlights the absence of consensus between organised breast screening programmes incorporating MBD in current breast screening protocols.

6.
J Neurosurg Pediatr ; 28(3): 351-359, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34214976

RESUMO

OBJECTIVE: Isolated anterior cerebral artery (ACA) territory ischemia in pediatric moyamoya disease (MMD) is rare but has been increasingly recognized, particularly in children manifesting progression of disease in a delayed fashion after middle cerebral artery revascularization surgery. Surgical treatment is complicated by limited graft choices, with the small number of case series largely focused on complex, higher-risk operations (omental flap transfers, large interhemispheric rotational grafts); direct bypass (often untenable in children due to vessel size); or, alternatively, the technically simpler method of multiple burr holes (of limited efficacy outside of infants). Faced with the problem of a growing cohort of pediatric patients with MMD that could benefit from anterior cerebral revascularization, the authors sought to develop a solution that was specifically designed for children and that would be lower risk than the more complex approaches adapted from adult populations but more effective than simple burr holes. In this study, the authors aimed to describe the long-term clinical and radiographic outcomes of a novel approach of pial pericranial dural (PiPeD) revascularization, building on the principles of pial synangiosis but unique in using the pericranium and the dura mater as the primary vascular supply, and employing a larger craniotomy with arachnoid dissection to provide robust full-territory revascularization in all ages with reduced risk relative to more complex procedures. METHODS: The medical records of all pediatric patients with MMD who presented at a single center between July 2009 and August 2019 were retrospectively reviewed to identify patients with MMD with anterior cerebral territory ischemia. Clinical characteristics, surgical indications, operative techniques, and long-term clinical and radiographic follow-up data were collected and analyzed. RESULTS: A total of 25 operations (5.6% of total procedures) were performed in 21 patients (mean age 9.4 years [range 1-16.5 years]; 12 female and 9 male). Almost one-third of the patients had syndromic associations, with no familial cases. Complications included 1 patient (4.7%) with a superficial infection, with no postoperative strokes, hemorrhage, seizures, or deaths. Long-term follow-up was available in 18 of 21 patients (mean 24.9 months [range 4-60 months]). Radiographic engraftment was present in 90.9% (20/22 hemispheres), and no new strokes were evident on MRI on long-term follow-up, despite radiographic progression of the disease. CONCLUSIONS: The use of the pericranium and the dura mater for indirect revascularization provided robust vascularized graft with great flexibility in location and high potential for engraftment, which may obviate more complex and higher-risk operations for ACA territory ischemia. Long-term follow-up demonstrated that PiPeD revascularization conferred durable, long-term radiographic and clinical protection from stroke in pediatric patients with MMD. Based on the results of the current study, the PiPeD technique can be considered an additional tool to the armamentarium of indirect revascularization procedures in select pediatric patients with MMD.

7.
Front Neurol ; 12: 661952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868159

RESUMO

Introduction: A major difficulty in treating moyamoya disease is the lack of effective methods to detect novel or progressive disease prior to the onset of disabling stroke. More importantly, a tool to better stratify operative candidates and quantify response to therapy could substantively complement existing methods. Here, we present proof-of-principle data supporting the use of urinary biomarkers as diagnostic adjuncts in pediatric moyamoya patients. Methods: Urine and cerebrospinal fluid specimens were collected from pediatric patients with moyamoya disease and a cohort of age and sex-matched control patients. Clinical and radiographic data were paired with measurements of a previously validated panel of angiogenic proteins quantified by ELISA. Results were compared to age and sex-matched controls and subjected to statistical analyses. Results: Evaluation of a specific panel of urinary and cerebrospinal fluid biomarkers by ELISA demonstrated significant elevations of angiogenic proteins in samples from moyamoya patients compared to matched controls. ROC curves for individual urinary biomarkers, including MMP-2, MMP-9, MMP-9/NGAL, and VEGF, showed excellent discrimination. The optimal urinary biomarker was MMP-2, providing a sensitivity of 88%, specificity of 100%, and overall accuracy of 91%. Biomarker levels changed in response to therapy and correlated with radiographic evidence of revascularization. Conclusions: We report, for the first time, identification of a panel of urinary biomarkers that predicts the presence of moyamoya disease. These biomarkers correlate with presence of disease and can be tracked from the central nervous system to urine. These data support the hypothesis that urinary proteins are useful predictors of the presence of moyamoya disease and may provide a basis for a novel, non-invasive method to identify new disease and monitor known patients following treatment.

9.
Environ Monit Assess ; 192(7): 458, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32594332

RESUMO

The US Geological Survey (USGS) is currently (2020) integrating its water science programs to better address the nation's greatest water resource challenges now and into the future. This integration will rely, in part, on data from 10 or more intensively monitored river basins from across the USA. A team of USGS scientists was convened to develop a systematic, quantitative approach to prioritize candidate basins for this monitoring investment to ensure that, as a group, the 10 basins will support the assessment and forecasting objectives of the major USGS water science programs. Candidate basins were the level-4 hydrologic units (HUC04) with some of the smaller HUC04s being combined; median candidate-basin area is 46,600 km2. Candidate basins for the contiguous United States (CONUS) were grouped into 18 hydrologic regions. Ten geospatial variables representing land use, climate change, water use, water-balance components, streamflow alteration, fire risk, and ecosystem sensitivity were selected to rank candidate basins within each of the 18 hydrologic regions. The two highest ranking candidate basins in each of the 18 regions were identified as finalists for selection as "Integrated Water Science Basins"; final selection will consider input from a variety of stakeholders. The regional framework, with only one basin selected per region, ensures that as a group, the basins represent the range in major drivers of the hydrologic cycle. Ranking within each region, primarily based on anthropogenic stressors of water resources, ensures that settings representing important water-resource challenges for the nation will be studied.


Assuntos
Ecossistema , Rios , Monitoramento Ambiental , Hidrologia , Inquéritos e Questionários
10.
Radiat Prot Dosimetry ; 189(4): 420-427, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32363403

RESUMO

PURPOSE: To determine the influence of optimal collimation during lumbar spine radiography on radiation dose and image quality. MATERIAL AND METHODS: 110 lumbar spine patients were split into two groups-the first imaged with standard collimation and the second with optimal collimation. Body mass index, image field size, exposure conditions and dose area product were measured. Effective and absorbed organ doses were calculated. Image quality was assessed. RESULTS: Optimal collimation reduced the primary field by up to 40%. The effective dose was reduced by 48% for the AP projection, while no differences were found for the LAT projection due to incorrect positioning of the central beam with standard collimation. The absorbed dose to selected radiosensitive organs decreased by 41 and 10% in the AP and LAT projections, respectively. Image quality for the LAT projection improved by 24% and maintained for the AP projection. CONCLUSION: Optimal collimation in lumbar spine imaging significantly influences patient exposure to radiation.


Assuntos
Vértebras Lombares , Humanos , Vértebras Lombares/diagnóstico por imagem , Imagens de Fantasmas , Doses de Radiação , Radiografia
11.
Exp Mol Med ; 52(4): 658-671, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32286515

RESUMO

We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2:EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n = 30), other cerebrovascular disease (n = 14) and control patients (n = 29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p = 0.04) and migration (p = 0.08), impaired tube formation (p = 0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p = 0.03 and p < 0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2 > 25.7 pg/µg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Post-treatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.


Assuntos
Biomarcadores , Células Endoteliais/metabolismo , Efrina-B2/genética , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/etiologia , Receptor EphB4/genética , Células Cultivadas , Criança , Efrina-B2/metabolismo , Expressão Gênica , Humanos , Malformações Arteriovenosas Intracranianas/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Receptor EphB4/metabolismo
12.
Isr J Health Policy Res ; 8(1): 5, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609944

RESUMO

The implementation of a new role in healthcare teams frequently emanates from emerging or changing needs in the care delivery system or expressed needs of clinicians, patients or caregivers. In this commentary on the experience of the nurse coordinator role in Israel we suggest based on similar experiences in the United States, that effective implementation is accomplished when the functions of the role are well delineated with respect to other members of the team and informed by the needs of patients, their caregivers and clinicians. The outcomes expected from those performing the role should be established and measured over time.


Assuntos
Enfermeiras Clínicas , Papel do Profissional de Enfermagem , Humanos , Israel , Equipe de Assistência ao Paciente , Percepção , Estados Unidos
13.
BMC Public Health ; 18(1): 1390, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567520

RESUMO

BACKGROUND: Calcium intake during early adolescence falls short of requirements for maximum bone accretion. Parents and the home food environment potentially influence children's calcium intakes. This study aimed to quantify parental psychosocial factors (PSF) predicting calcium intakes of Asian, Hispanic, and non-Hispanic white (NHW) early adolescent children from a parental perspective. METHODS: This was a cross-sectional study involving the administration of a validated calcium-specific food frequency questionnaire to a convenience sample of children aged 10-13 years and the primary individual responsible for food acquisition in the child's household. Based on Social Cognitive Theory, parental factors potentially associated with children's calcium intake were also assessed via parent questionnaires. The total study sample consisted of 633 parent-child pairs (Asian = 110, Hispanic = 239, NHW = 284). Questionnaires were completed at community-based centers/sites. Outcome measures were the association between parent-child calcium (mg), milk (cups/day), and soda (cans/day) intakes and the predictive value of significant parental PSF towards calcium intakes of their children. Sex-adjusted linear regression and multivariate analyses were performed. RESULTS: Calcium intakes of parent-child pairs were positively associated among all ethnic groups (r = 0.296; P < 0.001). Soda intakes were positively associated among Hispanic parent-child pairs only (r = 0.343; P < 0.001). Home availability of calcium-rich foods (CRF), parental rules and expectations for their child's intake of beverages, and parents' calcium intake/role modeling were positively associated with children's calcium intake and overwhelmed all other PSF in multivariate analyses. Significant cultural differences were observed. Parental role modeling was a significant factor among Hispanic dyads only. Multivariate models explained 19-21% of the variance in children's calcium intakes. CONCLUSIONS: Nutrition interventions to improve children's calcium intakes should focus on parents and provide guidance on improving home availability of CRF and increasing rules and expectations for the consumption of CRF. Among Hispanic families, interventions promoting parental modeling of desired dietary behaviors may be most successful.


Assuntos
Povo Asiático/estatística & dados numéricos , Cálcio da Dieta/administração & dosagem , Características da Família/etnologia , Hispânico ou Latino/estatística & dados numéricos , Relações Pais-Filho/etnologia , Pais/psicologia , População Branca/estatística & dados numéricos , Adolescente , Criança , Estudos Transversais , Inquéritos sobre Dietas , Feminino , Humanos , Masculino
14.
Cancer ; 124(11): 2438-2446, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29537491

RESUMO

BACKGROUND: Although sexual dysfunction is common after hematopoietic stem cell transplantation (HCT), interventions to address sexual function are lacking. METHODS: We conducted a pilot study to assess the feasibility and preliminary efficacy of a multimodal intervention to address sexual dysfunction in allogeneic HCT survivors. Transplant clinicians screened HCT survivors ≥3 months post-HCT for sexual dysfunction causing distress. Those who screened positive attended monthly visits with a trained transplant clinician who: 1) performed an assessment of the causes of sexual dysfunction; 2) educated and empowered the patient to address his or her sexual concerns; and 3) implemented therapeutic interventions targeting the patient's needs. Feasibility was defined as having approximately 75% of patients who screened positive agreeing to participate and 80% attending at least 2 intervention visits. We administered the Patient-Reported Outcomes Measurement Information System (PROMIS) sexual function and satisfaction measure, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS) to evaluate sexual function, quality of life (QOL), and mood, respectively, at baseline and 6 months postintervention. RESULTS: Approximately 33.1% of patients (50 of 151 patients) screened positive for sexual dysfunction causing distress and 94.0% (47 of 50 patients) agreed to participate, with 100% attending 2 intervention visits. Participants reported improvements in satisfaction (P<.0001) and interest in sex (P<.0001), as well as orgasm (P<.0001), erectile function (P<.0001), vaginal lubrication (P = .0001), and vaginal discomfort (P = .0005). At baseline, approximately 32.6% of participants were not sexually active, compared with 6.5% after the intervention (P = .0005). Participants reported improvement in their QOL (P<.0001), depression (P = .0002), and anxiety (P = .0019). CONCLUSIONS: A multimodal intervention to address sexual dysfunction integrated within the transplant clinic is feasible with encouraging preliminary efficacy for improving sexual function, QOL, and mood in HCT survivors. Cancer 2018;124:2438-46. © 2018 American Cancer Society.


Assuntos
Sobreviventes de Câncer/psicologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Qualidade de Vida , Disfunções Sexuais Fisiológicas/reabilitação , Estresse Psicológico/reabilitação , Adulto , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Terapia Combinada/métodos , Estudos de Viabilidade , Feminino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente/estatística & dados numéricos , Projetos Piloto , Comportamento Sexual/fisiologia , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Fisiológicas/psicologia , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Resultado do Tratamento
15.
Biol Blood Marrow Transplant ; 22(1): 80-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26260679

RESUMO

Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD.


Assuntos
Nucleotídeos de Adenina/administração & dosagem , Arabinonucleosídeos/administração & dosagem , Bussulfano/administração & dosagem , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Condicionamento Pré-Transplante , Adulto , Idoso , Doença Crônica , Clofarabina , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
16.
Biol Blood Marrow Transplant ; 21(9): 1583-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26009261

RESUMO

Many patients with lymphoma relapse after autologous stem cell transplantation (AutoSCT). These patients are often considered for allogeneic stem cell transplantation (AlloSCT) if remission can be achieved. If a tandem approach was organized, some cases of relapse might be prevented. We conducted a phase II trial of tandem AutoSCT followed by reduced-intensity conditioning (RIC) AlloSCT for patients with high-risk lymphoma. High-dose chemotherapy was given with busulfan, cyclophosphamide, and etoposide. AlloSCT was composed of RIC with busulfan/fludarabine and tacrolimus, sirolimus, and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Donors were fully matched related or unrelated donors. AlloSCT was performed any time between 40 days and 6 months after AutoSCT. Forty-two patients were enrolled, and all patients underwent AutoSCT. RIC AlloSCT was performed in 29 patients. In the 29 patients who underwent tandem transplant, median time from AutoSCT to AlloSCT was 96 days (range, 48 to 169). The 6-month cumulative incidence of grades II to IV acute GVHD was 13.8% (90% confidence interval [CI], 5.3% to 26.3%). Cumulative incidence of chronic GVHD at 1 year was 37.9% (90% CI, 23.1% to 52.7%). Nonrelapse mortality at 2 years after AlloSCT was 11.1% (90% CI, 3.5% to 23.6%). At a median follow-up of 30 months (range, 17.1 to 51.5) for the entire group, the 2-year progression-free survival rate was 64% (90% CI, 50% to 75%) and the 2-year overall survival rate was 69% (90% CI, 43% to 85%). For the 29 patients who underwent tandem SCT, the 2-year progression-free survival rate was 72% (90% CI, 55% to 83%) and the 2-year OS rate was 89% (90% CI, 74% to 96%). Tandem AutoSCT-RIC AlloSCT appears to be safe and effective in patients with high-risk lymphoma. Prospective trials using such an approach in specific lymphoma subtypes are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma/mortalidade , Linfoma/terapia , Transplante de Células-Tronco , Adulto , Idoso , Aloenxertos , Autoenxertos , Bussulfano/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Sirolimo/administração & dosagem , Taxa de Sobrevida , Tacrolimo/administração & dosagem , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
17.
Cancer ; 121(2): 226-33, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25204639

RESUMO

BACKGROUND: High-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL. METHODS: A single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m(2) were given on days 1 and 8 of mobilization and on days -9 and -2 of TBC. The primary endpoint was efficacy. RESULTS: Thirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma. CONCLUSIONS: For patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Indução/métodos , Linfoma não Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/cirurgia , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Massachusetts , Pessoa de Meia-Idade , Rituximab , Tiotepa/administração & dosagem , Transplante Autólogo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...