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1.
ESMO Open ; 9(7): 103626, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38968929

RESUMO

BACKGROUND: Determining the maximum tolerated dose (MTD) remains the primary objective for the majority of dose-finding oncology trials. Whilst MTD determination often relies upon clinicians to identify dose-limiting toxicities (DLTs) experienced by patients during the trial, research suggests that clinicians may underreport patient's adverse events. Therefore, contemporary practice may be exposed to recommending intolerable doses to patients for further investigation in subsequent trials. There is increasing interest in patients self-assessing their own symptoms using patient-reported outcomes (PROs) in dose-finding trials. DESIGN: We present Utility-PRO-Continual Reassessment Method (U-PRO-CRM), a novel trial design which simultaneously uses clinician-rated and patient-rated DLTs (Clinician-DLTs and Patient-DLTs, respectively) to make dose (de-)escalation decisions and to recommend an MTD. U-PRO-CRM contains the published PRO-CRM as a special case and provides greater flexibility to trade-off the rate of Patient-DLTs and Clinician-DLTs to find an optimal dose. We present simulation results for U-PRO-CRM. RESULTS: For specified trade-offs between Clinician-DLT and Patient-DLT rate, U-PRO-CRM outperforms the PRO-CRM design by identifying the true MTD more often. In the special case where U-PRO-CRM generalises to PRO-CRM, U-PRO-CRM performs as well as its published counterpart. U-PRO-CRM minimises the number of patients overdosed whilst maintaining a similar proportion of patients allocated to the true MTD. CONCLUSIONS: By using a utility-based dose selection approach, U-PRO-CRM offers the flexibility to define a trade-off between the risk of patient-rated and clinician-rated DLTs for an optimal dose. Patient-centric dose-finding strategies, which integrate PROs, are poised to assume an ever more pivotal role in significantly advancing our understanding of treatment tolerability. This bears significant implications in shaping the future landscape of early-phase trials.

2.
IBM J Res Dev ; 62(1)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29875505

RESUMO

An increasing number of people use mobile devices to monitor their behavior, such as exercise, and record their health status, such as psychological stress. However, these devices rarely provide ongoing support to help users understand how their behavior contributes to changes in their health status. To address this challenge, we aim to develop an interpretable policy for physical activity recommendations that reduce a user's perceived psychological stress, over a given time horizon. We formulate this problem as a sequential decision-making problem and solve it using a new method that we refer to as threshold Q-learning (TQL). The advantage of the TQL method over traditional Q-learning is that it is "doubly robust" and interpretable. This interpretability is achieved by making model assumptions and incorporating threshold selection into the learning process. Our simulation results indicate that the TQL method performs better than the Q-learning method given model misspecification. Our analyses are performed on data collected from 79 healthy adults over a 7 week period, where the data comprise physical activity patterns collected from mobile devices and self-assessed stress levels of the users. This work serves as a first step toward a computational health coaching solution for mobile device users.

3.
Yearb Med Inform ; 26(1): 160-171, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28480472

RESUMO

Introduction: Various health-related data, subsequently called Person Generated Health Data (PGHD), is being collected by patients or presumably healthy individuals as well as about them as much as they become available as measurable properties in their work, home, and other environments. Despite that such data was originally just collected and used for dedicated predefined purposes, more recently it is regarded as untapped resources that call for secondary use. Method: Since the secondary use of PGHD is still at its early evolving stage, we have chosen, in this paper, to produce an outline of best practices, as opposed to a systematic review. To this end, we identified key directions of secondary use and invited protagonists of each of these directions to present their takes on the primary and secondary use of PGHD in their sub-fields. We then put secondary use in a wider perspective of overarching themes such as privacy, interpretability, interoperability, utility, and ethics. Results: We present the primary and secondary use of PGHD in four focus areas: (1) making sense of PGHD in augmented Shared Care Plans for care coordination across multiple conditions; (2) making sense of PGHD from patient-held sensors to inform cancer care; (3) fitting situational use of PGHD to evaluate personal informatics tools in adaptive concurrent trials; (4) making sense of environment risk exposure data in an integrated context with clinical and omics-data for biomedical research. Discussion: Fast technological progress in all the four focus areas calls for a societal debate and decision-making process on a multitude of challenges: how emerging or foreseeable results transform privacy; how new data modalities can be interpreted in light of clinical data and vice versa; how the sheer mass and partially abstract mathematical properties of the achieved insights can be interpreted to a broad public and can consequently facilitate the development of patient-centered services; and how the remaining risks and uncertainties can be evaluated against new benefits. This paper is an initial summary of the status quo of the challenges and proposals that address these issues. The opportunities and barriers identified can serve as action items individuals can bring to their organizations when facing challenges to add value from the secondary use of patient-generated health data.


Assuntos
Informática Aplicada à Saúde dos Consumidores , Aplicações da Informática Médica , Pesquisa Biomédica , Humanos , Informática Médica
4.
Biosens Bioelectron ; 93: 212-219, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27660018

RESUMO

Sepsis by bacterial infection causes high mortality in patients in intensive care unit (ICU). Rapid identification of bacterial infection is essential to ensure early appropriate administration of antibiotics to save lives of patients, yet the present benchtop molecular diagnosis is time-consuming and labor-intensive, which limits the treatment efficiency especially when the number of samples to be tested is extensive. Therefore, we hereby report a microfluidic platform lab-on-a-disc (LOAD) to provide a sample-to-answer solution. Our LOAD customized design of microfluidic channels allows automation to mimic sequential analytical steps in benchtop environment. It relies on a simple but controllable centrifugation force for the actuation of samples and reagents. Our LOAD system performs three major functions, namely DNA extraction, isothermal DNA amplification and real-time signal detection, in a predefined sequence. The disc is self-contained for conducting sample heating with chemical lysis buffer and silica microbeads are employed for DNA extraction from clinical specimens. Molecular diagnosis of specific target bacteria DNA sequences is then performed using a real-time loop-mediated isothermal amplification (RT-LAMP) with SYTO-9 as the signal reporter. Our LOAD system capable of bacterial identification of Mycobacterium tuberculosis (TB) and Acinetobacter baumanii (Ab) with the detection limits 103cfu/mL TB in sputum and 102cfu/mL Ab in blood within 2h after sample loading. The reported LOAD based on an integrated approach should address the growing needs for rapid point-of-care medical diagnosis in ICU.


Assuntos
Acinetobacter baumannii/isolamento & purificação , Técnicas Biossensoriais , DNA Bacteriano/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Sepse/microbiologia , Acinetobacter baumannii/patogenicidade , DNA Bacteriano/química , Humanos , Técnicas Analíticas Microfluídicas , Mycobacterium tuberculosis/patogenicidade , Compostos Orgânicos/química , Sepse/diagnóstico
5.
Br J Dermatol ; 171(1): 90-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24593191

RESUMO

BACKGROUND: The human leucocyte antigen (HLA) allele, HLA-A*31:01, is a biomarker for adverse cutaneous reactions to carbamazepine, a first-line antiepileptic drug. OBJECTIVES: To develop a platform that can rapidly detect the HLA-A*31:01 allele in blood samples to facilitate pretreatment screening. METHODS: A novel protocol based on loop-mediated isothermal amplification (LAMP) was designed and optimized. It was applied to purified genomic DNA samples derived from B-cell lines with known HLA genotypes, and to DNA and whole blood samples collected from patients with epilepsy, in whom HLA-A genotypes were determined by sequence-based typing. RESULTS: The turnaround time for the LAMP-based protocol was < 45 min. In the DNA samples derived from B-cell lines (n = 66), the sensitivity, specificity, positive predictive value and negative predictive value of the LAMP-based protocol for detecting HLA-A*31:01 were 1·00 [95% confidence interval (CI) 0·88-1·00], 0·95 (95% CI 0·82-0·99), 0·94 and 1·00, respectively. The LAMP-based protocol produced the same results in the DNA and whole blood samples collected from patients (n = 34). Its sensitivity, specificity, positive predictive value and negative predictive value in detecting HLA-A*31:01 in the patient samples were 1·00 (95% CI 0·57-1·00), 0·97 (95% CI 0·83-0·99), 0·83 and 1·00, respectively. CONCLUSIONS: The findings demonstrated the feasibility of accurately detecting HLA-A*31:01 in DNA and whole blood samples using a LAMP-based protocol. Given its rapid turnaround time, this novel platform has the potential to be adapted into a point-of-care screening test.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , DNA/análise , Antígenos HLA-A/análise , Técnicas de Amplificação de Ácido Nucleico/métodos , Alelos , Biomarcadores/análise , Biomarcadores/sangue , Linhagem Celular , Toxidermias/diagnóstico , Diagnóstico Precoce , Epilepsia/tratamento farmacológico , Estudos de Viabilidade , Triagem de Portadores Genéticos/métodos , Antígenos HLA-A/sangue , Antígenos HLA-A/genética , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade
6.
Hong Kong Med J ; 18 Suppl 2: 17-21, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22311355

RESUMO

1. Two novel HLA-A2.1 specific H5N1 nucleoprotein epitopes(NP373-381 AMDSNTLEL and NP458-466 FQGRGVFEL) capable of activating cytotoxic T-cells in vitro were identified. 2. When the H5N1 nucleoprotein epitopes (NP373-381AMDSNTLEL and NP458-466FQGRGVFEL) were used with the single chain trimer system, they elicited effective cytotoxic T-cell responses against the corresponding nucleoprotein peptide-loaded cells in an HHD transgenic mouse model.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/farmacologia , Influenza Humana/imunologia , Nucleoproteínas/imunologia , Animais , Células Cultivadas , Citotoxicidade Imunológica , Epitopos de Linfócito T , Humanos , Interferon gama/metabolismo , Camundongos , Infecções por Orthomyxoviridae/imunologia
7.
Neurology ; 78(4): 250-5, 2012 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-22238418

RESUMO

OBJECTIVE: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.


Assuntos
Circulação Cerebrovascular , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Idoso , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/psicologia , Transtornos Cognitivos/diagnóstico por imagem , Estudos de Coortes , Escolaridade , Feminino , Lateralidade Funcional , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/fisiopatologia , Ataque Isquêmico Transitório/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Destreza Motora , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/psicologia , Teste de Sequência Alfanumérica , Percepção Visual , Testes de Associação de Palavras
8.
Ann Oncol ; 23(2): 537-41, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21536663

RESUMO

BACKGROUND: Toxicity data from cancer trials are summarized into a single outcome, dose-limiting toxicity (DLT), which does not account for multiple lower grade toxic effects nor differentiates between toxicity types and gradations within DLT. METHODS: Toxicity data were summarized into a toxicity burden score (TBS) using a weighted sum. The severity weights were estimated via regression using historical data. We demonstrated the method using historical data from a bortezomib trial and illustrated the advantages of defining DLT based on TBS in a simulated dose-finding trial. RESULTS: The estimated weights were 0.17, 0.40 and 0.85 for grade 1/2, grade 3 and grade 4 platelets, respectively; 0.19, 0.64, 1.03 and 2.53 for grade 1, 2, 3 and 4 neuropathy, respectively and 0.17 for each grade 3 or higher nonhematologic toxic effects unrelated to treatment. In the simulated trial, the probability of selecting doses above the maximum tolerated dose decreased when using the DLT defined based on TBS. CONCLUSIONS: TBS is a feasible approach to summarize toxicity. It includes information from the grades and types of multiple toxic effects and can be applied in all phases of drug development. Further efforts should focus on validating the method in a large prospective study before applying it in practice.


Assuntos
Antineoplásicos/toxicidade , Ácidos Borônicos/toxicidade , Neoplasias/tratamento farmacológico , Pirazinas/toxicidade , Testes de Toxicidade , Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Bortezomib , Estudos de Viabilidade , Indicadores Básicos de Saúde , Humanos , Pirazinas/efeitos adversos
9.
Ultrasound Obstet Gynecol ; 36(3): 362-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20603859

RESUMO

OBJECTIVES: To describe the sonographic findings in the decidua basalis layer in spontaneous early pregnancy loss and to compare them with those in normal pregnancy. METHODS: We reviewed 119 scans at 4-10 weeks' gestation from 110 patients who miscarried clinically at less than 13 weeks' gestation and 132 scans also at 4-10 weeks from 98 patients who had normal uncomplicated term pregnancies. The thickness and echogenicity of the decidua basalis layer were compared between pregnancies which suffered early loss and normal controls. RESULTS: Relative thinning of the decidua basalis was observed in cases of early pregnancy loss from 5-6 weeks onwards when compared with normal pregnancies. In embryonic pregnancies that subsequently miscarried, the decidua basalis did not show the rising trend in thickness that was observed in normal pregnancies. Shortly before and after embryonic demise, the decidua appeared relatively more echogenic compared with that in normal pregnancy and the placenta showed areas of hypoechogenicity. Embryonic demise was followed by disorganization of the decidual layer, which became difficult to recognize. Pregnancy with an empty sac showed a more gradual trend in the thinning of the decidua basalis, but the uniformity and echogenicity of the layer appeared to be relatively better preserved with time. CONCLUSION: The decidua basalis layer in pregnancies that are destined to miscarry in the first trimester differs sonographically from that in normal pregnancies. The sonographic differences are suggestive of a defective decidual-placental complex resulting from deficient trophoblastic invasion.


Assuntos
Aborto Espontâneo/diagnóstico por imagem , Decídua/diagnóstico por imagem , Placenta/diagnóstico por imagem , Trofoblastos/diagnóstico por imagem , Aborto Espontâneo/fisiopatologia , Adulto , Decídua/fisiopatologia , Feminino , Idade Gestacional , Humanos , Placenta/fisiopatologia , Gravidez , Primeiro Trimestre da Gravidez , Trofoblastos/fisiologia , Ultrassonografia Pré-Natal
10.
Ultrasound Obstet Gynecol ; 33(6): 634-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19291694

RESUMO

OBJECTIVES: To describe the sonographic appearance of the decidua basalis and its changes in the first trimester of pregnancy. METHODS: We reviewed images from 159 first-trimester ultrasound examinations in 105 women with uncomplicated pregnancies who later delivered at term. The appearance of the decidua basalis layer and the sonographic changes that it underwent, including in echogenicity and thickness, were analyzed with respect to gestational age. RESULTS: A distinct decidual layer could be identified consistently at 5-6 weeks' gestation and its thickness peaked at 6-7 weeks. It was seen inconsistently at 8-9 weeks and was not identifiable by 10 weeks. Its appearance changed over time, from a uniformly echogenic layer at 5-6 weeks to a heterogeneous echogenic layer at 7 weeks, corresponding to the histological evidence of trophoblast penetration. The layer then became less echogenic with time until it became unidentifiable. CONCLUSIONS: There is a window of opportunity in the first trimester for sonographic examination of the decidua. This may allow screening, at an early stage, for conditions that affect the decidua during pregnancy.


Assuntos
Decídua/diagnóstico por imagem , Trofoblastos/diagnóstico por imagem , Adolescente , Adulto , Decídua/fisiologia , Feminino , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Trofoblastos/fisiologia , Ultrassonografia Pré-Natal , Adulto Jovem
13.
Bone Marrow Transplant ; 40(7): 621-31, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17660841

RESUMO

There is a significant amount of morbidity and mortality following myeloablative umbilical cord blood transplantation (UCBT). Reduced intensity (RI) conditioning offers an alternative to myeloablative conditioning before UCBT. We investigated RI-UCBT in 21 children and adolescents with malignant (n=14), and non-malignant diseases (n=7). RI conditioning consisted of fludarabine (150-180 mg/m2) with either busulfan (< or = 8 mg/kg)+rabbit antithymocyte globulin (R-ATG; n=16) or cyclophosphamide+R-ATG+/-etoposide (n=5). Human leukocyte antigen match: 4/6 (n=13), 5/6 (n=5) and 6/6 (n=3). The median total nucleated cell and CD34+ cell dose per kilogram were 3.58 x 10(7) and 2.54 x 10(5), respectively. The median time for neutrophil and platelet engraftment was 17.5 and 52 days, respectively. There were six primary graft failures (chronic myelogenous leukemia (CML), beta-thalassemia, hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndrome (MDS)). The probability of developing grade II to grade IV acute graft-versus-host disease (GVHD) and chronic GVHD was 28.6 and 16.7%, respectively. Incidence of transplant-related mortality (TRM) was 14%. The 5 years overall survival (OS) in all patients was 59.8%. The 5 years OS for patients with average versus poor-risk malignancy was 77.8 versus 22.2% (P=0.03). RI-UCBT may result in graft failure in specific high-risk chemo-naïve patients (CML, beta-thalassemia, HLH and MDS), but in more heavily pretreated pediatric and adolescent recipients results in rapid engraftment and may be associated with decreased severe GVHD and TRM.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal/citologia , Neoplasias/terapia , Adolescente , Adulto , Antígenos CD34/análise , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/prevenção & controle , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Doadores Vivos , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Neoplasias/mortalidade , Seleção de Pacientes , Proteínas Recombinantes , Análise de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante , Falha de Tratamento , Resultado do Tratamento , Talassemia beta/mortalidade , Talassemia beta/terapia
16.
Biophys J ; 90(9): 3288-99, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16461393

RESUMO

Zero mode waveguides (ZMWs), subwavelength optical nanostructures with dimensions ranging from 50 to 200 nm, have been used to study systems involving ligand-receptor interactions. We show that under proper conditions, lipid membranes will invaginate into the nanostructures, which confine optical excitation to subattoliter volumes. Fluorescence correlation spectroscopy (FCS) was used to characterize the diffusion of fluorescently tagged lipids in liquid-disordered phase 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and gel phase 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) membranes incubated on the nanostructured surface. In contrast to the POPC, DSPC membranes did not appear to enter the structures, suggesting that invagination is dependent on membrane rigidity. Although correlation curves obtained from POPC membranes conformed to previously derived models for diffusion in the evanescent field within the nanostructure, the diffusion constants obtained were systematically lower than expected. The validity of the one-dimensional diffusion model for membrane diffusion is discussed and it is concluded that the erroneous diffusion constants are a result of nontrivial membrane conformation within the ZMWs. Additionally, FCS was used to characterize the fraction of fluorescently labeled tetanus toxin C fragment bound to a ganglioside-populated POPC membrane within the ZMWs. This allowed the determination of the toxin's equilibrium binding constant at a concentration of 500 nM; higher than possible with diffraction-limited FCS. To our knowledge, the results presented here are the first reported for supported lipid bilayers in nanostructured devices. Furthermore, they open the possibility of studying membrane imbedded receptors and proteins at physiological concentrations with single-molecule resolution.


Assuntos
Bicamadas Lipídicas/química , Fosfatidilcolinas , Gangliosídeos/química , Gangliosídeos/metabolismo , Modelos Biológicos , Nanoestruturas/química , Espectrometria de Fluorescência , Toxina Tetânica/química , Toxina Tetânica/metabolismo
18.
Gynecol Oncol ; 96(2): 475-83, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15661238

RESUMO

OBJECTIVE: To explore whether the recombinant protein (Human papillomavirus (HPV) type16 E7 peptide(38-61) linked with an immunoglobulin G fragment) will generate protective immunity in mouse model. METHODS: In our study, we combined the HPV16 E7 peptide(38-61) with a murine IgG heavy chain constant region to construct a chimeric protein compound, which was highly expressed as inclusion bodies in a bacterial expression system with Escherichia coli. The purified chimeric protein was injected into C57BL/6 mice and the efficiency of the chimeric vaccine candidate was evaluated by antibody response assay, T cell proliferation assay, CTL assay, tumor challenge assay and therapeutic experiment. RESULTS: The chimeric vaccine candidate was able to induce anti-HPV antibodies as well as to elicit HPV16 E7-specific CTLs and T cell proliferation in a pre-clinical mouse model. It was also able to effectively protect mice against the challenge of HPV16-positive tumor cells, and to eradicate HPV16-expressing tumors in mice. CONCLUSIONS: The chimeric protein vaccine can induce E7-specific immune responses and protect mice against challenge of HPV16-positive tumor, even eradicate developed tumor. The results indicated a possibility to use the chimeric protein vaccine to protect human against HPV infection.


Assuntos
Vacinas Anticâncer/imunologia , Imunoglobulina G/imunologia , Neoplasias Experimentais/imunologia , Proteínas Oncogênicas Virais/imunologia , Proteínas Recombinantes de Fusão/imunologia , Animais , Anticorpos Antineoplásicos/biossíntese , Anticorpos Antineoplásicos/imunologia , Formação de Anticorpos , Vacinas Anticâncer/biossíntese , Vacinas Anticâncer/genética , Vacinas Anticâncer/isolamento & purificação , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Fragmentos de Imunoglobulinas/genética , Fragmentos de Imunoglobulinas/imunologia , Imunoglobulina G/genética , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/prevenção & controle , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia
19.
Bone Marrow Transplant ; 34(2): 129-36, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15107815

RESUMO

We report results of unrelated cord blood transplants (UCBT) in 29 pediatric recipients in one center and the risk factors associated with survival. Median age: 9 years (0.5-20); diagnosis: ALL (9), AML (4), CML (1), HD (3), HLH (1), NHL (3), NBL (2); B-thal (1), FA (1), FEL (1), Krabbe (1), WAS (1), SAA (1); median follow-up: 11 months; conditioning: total body irradiation (TBI)-ablative (14), chemotherapy-ablative (6) and reduced intensity chemotherapy (9); GVHD prophylaxis: MMF/FK506 (18), cyclosporin A (CsA)+steroids+/-MMF (7) or CsA+methotrexate (MTX) (4); median total nucleated cells (TNC): 3.8 x 10(7)/kg (1.1-11); median CD34+: 2.3 x 10(5)/kg (0.2-9.9); and HLA match: 2 (6/6), 5 (5/6), 22 (4/6). Neutrophil engraftment by cumulative incidence curves 63% (median 28 (95% confidence interval (CI) 18-32)). Probability of >/=grade II acute graft-versus-host disease (aGVHD) by day +60 27%, >/=grade III aGVHD 20% and chronic graft-versus-host disease 3%. Estimated 1-year overall survival (OS) 46% (95% CI 30-71) and standard risk 60% (95% CI 29-100%). Variables associated with improved survival by multivariate analysis include non-TBI-ablative conditioning (P=0.024), CD34+/kg (P=0.038) and gender (P=0.048). These results suggest that CD34/kg cell dose and non-TBI-ablative conditioning may be important variables influencing OS following UCBT in pediatric recipients. Given the small number of patients, these results should be viewed cautiously.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Adolescente , Adulto , Antígenos CD34/análise , Doadores de Sangue , Criança , Pré-Escolar , Estudos de Coortes , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Probabilidade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
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