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1.
Br J Haematol ; 185(6): 1099-1110, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30714126

RESUMO

Progress in overall survival rates for childhood non-Hodgkin lymphoma (NHL) can be largely attributed to effective development and conduct of a number of international treatment studies. Knowledge gained from these studies has shifted the treatment paradigm from a "one-size fits all" strategy to a histologically dependent approach. More specifically, many now adhere to a risk-stratified approach, prescribing cumulative doses and intensities of chemotherapeutic exposures based upon the aggressiveness of disease. Moreover, recognition that high cure rates could be achieved without the use of radiation has eliminated the use of this modality in frontline settings for the majority of newly diagnosed children. These changes have contributed to the emergence of a heterogeneous group of NHL survivors. As the number of NHL survivors continues to increase, providers will encounter a wide spectrum of individuals whose risk for long-term complications are accordingly diverse. The following review summarizes the existing literature surrounding late effects, such as chronic health conditions, functional and neurocognitive performance outcomes, and health-related quality of life, that are unique to NHL survivors, as well as those extrapolated from the broader childhood cancer survivor population.

2.
Cancer J ; 24(6): 285-300, 2018 Nov/Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30480573

RESUMO

Lymphomas in adolescents and young adults represent approximately one quarter of all cancers in this age group. Historically, adolescent and young adult cancer patients represent a unique population with diverging issues surrounding psychosocial hardships/barriers, economics, and lack of standardization of therapeutic approaches.Furthermore, the biologic differences within the adolescent and young adult population seen in various lymphoma subtypes likely play a role in overall outcomes for this group. Without an organized approach to clinical and translational research for adolescent and young adult patients within specialized treatment centers, this population may continue to experience inferior results. Here we look at the current perspectives of adolescent and young adult lymphomas with respect to disease biology, clinical characteristics, treatment, and prognosis of this unique lymphoma population.

3.
Artigo em Inglês | MEDLINE | ID: mdl-29899571

RESUMO

Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 - 52 mg/m2), cytarabine 1000 mg/m2, and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1-22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI95: 23-54%), and 41.3% (CI95: 25-57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI95: 1.35-9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI95: 1.33-4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.

4.
Pediatr Blood Cancer ; 65(8): e27073, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29741220

RESUMO

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies with high incidence in adolescents and young adults (AYAs). The most common diseases include diffuse large B-cell lymphoma, anaplastic large cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and primary mediastinal large B-cell lymphoma. In comparison to younger children and adults, AYAs (15-39 years) with NHL present a specific set of challenges including variations in tumor biology, inconsistent treatment, pharmacodynamics, and psychosocial barriers. While survival of AYAs with NHL has improved, cure rates remain suboptimal. Incorporation of novel agents into pediatric-inspired treatment regimens specifically designed for NHL in AYAs has led to improved outcomes. Consideration of AYAs as a distinct population in the diagnosis and treatment of NHL is encouraged.

5.
Oncotarget ; 9(11): 9776-9788, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29515770

RESUMO

Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBL) share similar molecular features by gene expression profiling. Frequent gains of chromosome 9p exhibit higher Janus Kinase 2 (JAK2) transcript levels with increased JAK2 activity, suggesting aberrant activity of JAK2 and STAT pathways. This signaling pathway alteration may in part play an important role in the pathogenesis and/or chemoradiotherapy resistance in HL and PMBL. Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor, with activity against myeloproliferative neoplasms (MPNs) including those harboring the JAK2V617F mutation. We investigated the in vitro and in vivo efficacy of ruxolitinib and changes in downstream signaling pathways in HL and PMBL. We demonstrated that ruxolitinib significantly inhibited STAT signaling in both HL and PMBL with constitutively active JAK2 signaling. We also observed that ruxolitinib significantly induced in vitro anti-proliferative effects (p < 0.05) and increased programmed cell death (p < 0.05) against both HL and PMBL cells. Importantly, ruxolitinib significantly inhibited tumor progression by bioluminescence (p < 0.05) and significantly improved survival in HL (p = 0.0001) and PMBL (p < 0.0001) xenograft NSG mice. Taken altogether, these studies suggest that ruxolitinib may be a potential adjuvant targeted agent in the therapeutic approach in patients with high risk HL and PMBL.

6.
Leuk Lymphoma ; 59(10): 2360-2368, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29431566

RESUMO

Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted.

7.
Exp Hematol ; 46: 38-47, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27765614

RESUMO

Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562). NK cell expansion; expression of lysosome-associated membrane protein-1 (LAMP-1), granzyme B, and perforin; and in vitro and in vivo cytotoxicity against B-cell non-Hodgkin lymphoma (B-NHL) were evaluated. In vivo tumor growth in B-NHL-xenografted nonobese diabetic severe combined immune deficient (NOD-scid) gamma (NSG) mice was monitored by tumor volume, cell number, and survival. CB MNCs cultured with MODK562 compared with WTK562 demonstrated significantly increased NK expansion (thirty-fivefold, p < 0.05); LAMP-1 (p < 0.05), granzyme B, and perforin expression (p < 0.001); and in vitro cytotoxicity against B-NHL (p < 0.01). Xenografted mice treated with MODK562 CB experienced significantly decreased B-NHL tumor volume (p = 0.0086) and B-NHL cell numbers (p < 0.01) at 5 weeks and significantly increased survival (p < 0.001) at 10 weeks compared with WTK562. In summary, MODK562 significantly enhanced CB NK expansion and cytotoxicity, enhanced survival in a human Burkitt's lymphoma xenograft NSG model, and could be used in the future as adoptive cellular immunotherapy after umbilical CB transplantation. Future directions include expanding anti-CD20 chimeric receptor-modified CB NK cells to enhance B-NHL targeting in vitro and in vivo.


Assuntos
Engenharia Celular , Sangue Fetal/citologia , Engenharia Genética , Células K562/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Animais , Biomarcadores , Comunicação Celular , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular , Citotoxicidade Imunológica , Granzimas/metabolismo , Xenoenxertos , Humanos , Imunoterapia Adotiva/métodos , Leucócitos Mononucleares , Ativação Linfocitária/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Camundongos , Camundongos Knockout , Perforina/metabolismo , Receptores de Células Matadoras Naturais/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Br J Haematol ; 173(4): 637-50, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27071675

RESUMO

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies accounting for a significant portion of cancers occurring in children, adolescents and young adults with an increasing incidence with age. The adolescent and young adult (AYA) population presents a specific set of characteristics and challenges. The most common diseases occurring in adolescents and young adults include Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, anaplastic large cell lymphoma and primary mediastinal B-cell lymphoma. There is also a higher incidence of primary central nervous system lymphoma in AYA patients. Cure rates largely depend on risk-stratification, and are generally superior to outcomes in comparison to older adult data but less than in younger children. Here, we review the unique clinical and biological characteristics of NHL occurring in the AYA population with a focus on how to achieve similar curative outcomes in AYA that have been established in younger cohorts.


Assuntos
Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Neoplasias do Sistema Nervoso Central , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Masculino , Medição de Risco , Resultado do Tratamento , Adulto Jovem
9.
J Glaucoma ; 24(8): 561-7, 2015 Oct-Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24777046

RESUMO

PURPOSE: To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. METHODS: One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. RESULTS: For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. CONCLUSIONS: The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.


Assuntos
Glaucoma/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Polarimetria de Varredura a Laser , Testes de Campo Visual/métodos , Idoso , Área Sob a Curva , Diagnóstico Precoce , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Sensibilidade e Especificidade
10.
Cancer Immunol Res ; 3(4): 333-44, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25492700

RESUMO

The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20(+) B-NHL in vitro and in vivo. CAR(+) exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR(-) exPBNK against CD20(+) Ramos (P < 0.05), Daudi, Raji, and two rituximab-resistant cell lines, Raji-2R and Raji-4RH (P < 0.001). As expected, there was no significant difference against CD20(-) RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production were also enhanced in CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR(-) exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P < 0.001) and reduced tumor size, compared with those of the untreated and the CAR(-) exPBNK-treated mice (P < 0.05). These preclinical data suggest that ex vivo-exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies.


Assuntos
Antígenos CD20/imunologia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Linfoma de Células B/terapia , Animais , Antígenos CD20/análise , Antígenos CD20/genética , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/terapia , Movimento Celular/imunologia , Citotoxicidade Imunológica , Humanos , Células Matadoras Naturais/transplante , Linfoma de Células B/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Mensageiro/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Clin Lymphoma Myeloma Leuk ; 14 Suppl: S6-13, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25486958

RESUMO

Although the event-free survival for children and adolescents with acute lymphoblastic leukemia (ALL) has dramatically improved over the past half century, it has plateaued over the past decade. Children and adolescents with refractory/relapsed ALL continue to have a dismal prognosis with hematopoietic stem cell transplant being their most viable option for cure. There is an obvious need for the development of novel agents to further enhance overall outcomes. In this review we focus on the development of humoral and cellular immunotherapeutic agents in the treatment of childhood, adolescent, and young adult ALL. Immunotherapy in various forms has shown immense promise. To date we have seen numerous safety studies using monoclonal antibody therapy, antibody conjugates, bispecific T cell and bispecific natural killer (NK) cell antibodies and genetically reengineered T and NK cells expressing targeted chimeric antigen receptors. Initial success has been found with the anti-CD20 monoclonal antibodies followed by promising results using anti-CD22 and anti-CD19 therapies alone or in combination. Genetic modification of T and NK cells to express targeted chimeric antigen receptors offers a novel immunotherapy option that demonstrates enhanced cytotoxicity in otherwise resistant tumor cells. There is great potential to combine immunotherapies to further improve overall cure rates in children, adolescents, and young adults with poor-risk ALL. A number of humoral and cellular immunotherapy strategies have been investigated and found to be effective, safe, and well tolerated. Ideally, the targeted approach of immunotherapy will result in an overall decrease in toxicities experienced by patients. Future studies are required to determine when in the course of treatment with humoral and cellular therapy will have the safest and optimal effect in ALL.


Assuntos
Imunoterapia/métodos , Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Transferência Adotiva , Adulto , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD19 , Antígenos CD20 , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos de Linfócitos T/genética , Proteínas Recombinantes de Fusão/genética , Rituximab , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/antagonistas & inibidores , Adulto Jovem
12.
Cardiol Rev ; 22(6): 268-74, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24926805

RESUMO

Improvements in the survival of children and adolescents diagnosed with cancer have resulted in a growing population of childhood, adolescent and adult cancer and stem cell transplant survivors. Approximately two thirds of these survivors will experience at least 1 late effect of their treatment, and about one third will experience a late effect that is severe or life threatening. Childhood cancer survivors are at high risk for development of severe cardiac disease, particularly after anthracycline and/or radiation exposure. Cardiotoxicity can present as early cardiac dysfunction during or shortly after therapy or as chronic impairment of cardiac function several years after treatment. Attempts to minimize serious adverse effects have included reduction of high-dose chemotherapy, particularly anthracycline dosing to <350 mg/m, use of cardioprotective agents such as dexrazoxane and decreased radiation dosing and radiation fields. There have been no convincing data showing medical interventions that can reliably slow or reverse cardiotoxicity in treated patients, which therefore warrants further studies looking at the use of beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or newer agents either prior to or following the discovery of heart damage. Emphasis on the prevention of further damage is critical and can be accomplished through aggressive surveillance, including screening for lipid abnormalities, cardiac biomarkers such as troponins and B-type natriuretic peptides, hypertension, diabetes and obesity as well as the use of echocardiography and cardiac magnetic resonance imaging to identify abnormalities early in their course. Here, we provide an overview of the field of cardio-oncology to stimulate interest among cardiologists.


Assuntos
Cardiopatias/etiologia , Neoplasias/terapia , Transplante de Células-Tronco/efeitos adversos , Sobreviventes , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores/metabolismo , Cardiotônicos/uso terapêutico , Criança , Ecocardiografia , Cardiopatias/diagnóstico , Humanos , Angiografia por Ressonância Magnética , Radioterapia/efeitos adversos , Fatores de Risco
13.
Br J Haematol ; 163(3): 365-72, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24032600

RESUMO

Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III-IV, bone marrow(+) and/or central nervous system(+) mature B-NHL received hydration and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well-tolerated and there were no grade III-IV toxicities probably or directly related to rasburicase. Patients with an initial lactate dehydrogenase ≥2× upper limit of normal had a significantly elevated uric acid level (P = 0·005), increased incidence of TLS (P-0·005) and lower glomerular filtration rate (GFR; P < 0·001). Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS, respectively. Furthermore, there was a significant improvement in estimated GFR from Day 0 to Day 7 following rasburicase (P = 0·0007) and only 1·3% of patients required new onset renal assisted support after rasburicase administration. A TLS strategy incorporating rasburicase prior to cytoreductive chemotherapy proved safe and effective in preventing new onset renal failure and was associated with a significant improvement in GFR.


Assuntos
Linfoma de Células B/complicações , Linfoma não Hodgkin/complicações , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/uso terapêutico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Adolescente , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Hiperuricemia/etiologia , Lactente , L-Lactato Desidrogenase/sangue , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/terapia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/terapia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Proteínas de Neoplasias/sangue , Projetos Piloto , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Rituximab , Síndrome de Lise Tumoral/sangue , Síndrome de Lise Tumoral/classificação , Urato Oxidase/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
14.
Br J Haematol ; 161(1): 27-42, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23384118

RESUMO

Most children, adolescents and young adults with acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) have an excellent prognosis with multi-agent chemotherapy in induction, consolidation, re-induction and maintenance therapy. However, there is a subset of patients with a more guarded prognosis using this approach, who may benefit from haematopoietic allogeneic stem cell transplantation (alloHSCT). Commonly used criteria for alloHSCT in children, adolescents and young adults with ALL in CR1 include: induction failure, poor cytogenetics, persistent minimal residual disease (MRD), age, immunophenotype, white blood cell count at diagnosis and rapidity of induction response. Two-year event-free survival following alloHSCT in patients with ALL in CR1 ranges from 50 to 80% depending on disease status, donor source, conditioning therapy, age and other risk factors. Future studies should focus on more precisely identifying poor-risk features, such as disease genomics and host pharmacogenomics, refining MRD measurements, improving unrelated donor matching, reducing MRD prior to alloHSCT, and developing post-alloHSCT humoral and cellular therapy approaches.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Humanos , Neoplasia Residual , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Indução de Remissão , Fatores de Risco , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Adulto Jovem
15.
Invest Ophthalmol Vis Sci ; 52(6): 3430-5, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-21357398

RESUMO

PURPOSE: To compare choroidal thickness measurements among normal eyes, eyes with normal tension glaucoma (NTG), and those with primary open-angle glaucoma (POAG), and to correlate choroidal thickness with demographic and clinical ocular parameters. METHODS: Choroidal thickness was measured with enhanced depth-imaging (EDI) optical coherence tomography (OCT) in one eye of 38 normal, 20 NTG, and 56 POAG subjects and compared among groups. The mean age was 69.3 ± 13.6 years (60.1 ± 13.4 years for normal subjects and 73.8 ± 11.3 years for glaucoma subjects; P < 0.001). Measurements were made at the fovea and in the temporal and nasal choroid every 0.5 mm up to 3 mm away from the fovea. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and demographic and ocular parameters. RESULTS: There were no differences in foveal, temporal, or nasal choroidal thickness between normal, NTG, and POAG subjects (all P > 0.05) after adjusting for age, axial length, and intraocular pressure. Similarly, glaucoma severity groups did not differ from each other in all choroidal thickness measurements (all P > 0.05). Age (ß = -1.78; P < 0.001) was the most significant factor associated with subfoveal choroidal thickness in the entire group, followed by axial length (ß = -11.8; P = 0.002). CONCLUSIONS: Choroidal thickness does not differ among normal, NTG, and POAG subjects, suggesting a lack of relationship between choroidal thickness and glaucoma based on EDI OCT measurements.


Assuntos
Corioide/patologia , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Baixa Tensão/diagnóstico , Tomografia de Coerência Óptica , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Comprimento Axial do Olho , Pesos e Medidas Corporais , Grupos Étnicos , Feminino , Cirurgia Filtrante , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/terapia , Humanos , Pressão Intraocular , Glaucoma de Baixa Tensão/etnologia , Glaucoma de Baixa Tensão/terapia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tonometria Ocular
17.
Exp Hematol ; 37(10): 1216-29, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19638292

RESUMO

OBJECTIVE: Cord blood (CB) is limited by the absence of available donor effector cells for post-unrelated CB transplantation adoptive cellular immunotherapy. We reported the ability to ex vivo expand (EvE) CB mononuclear cells (MNC) after short-term incubation with anti-CD3, interleukin (IL)-2, IL-7, and IL-12 (antibody/cytokine [AB/CY]) into subpopulations of CD3(-)/56(+) natural killer (NK) cells with enhanced in vitro and in vivo tumor cytotoxicity. MATERIALS AND METHODS: We compared 2- vs 7-day EvE of rethawed CB MNCs in AB/CY and activation of NK and NK-like T (NKT) cell (CD3(+)/56(+)) subsets expressing specific NK-cell receptors along with IL-15, IL-18, and interferon-gamma production. RESULTS: Nonadherent total cell number were significantly increased at day 7 (p<0.001) along with NK-cell number (20-fold) and an enrichment in NKT-like subsets (36-fold). There was no change in the NK(dim) subset; yet the NKT(bright) and NKT KIR3DL1(dim) subsets were significantly increased (p<0.05). NK cells expressing the inhibitory natural cytoxicity receptor CD94/NKG2A were decreased (p<0.001), while those expressing activating natural cytoxicity receptor CD94/NKG2D receptor and activating NK and NKT KIR2DS4 subsets were significantly increased (p<0.001). IL-18 and interferon-gamma protein production was also significantly increased (p<0.001 and p<0.05, respectively). Lysosomal-associated membrane protein-1 and granzyme B expression were increased (p<0.001 and p>0.01, respectively), which correlated with the significant increase in NK, LAK, and tumor cytotoxicity of the EvE cells. CONCLUSION: This study demonstrates that previously cryopreserved and rethawed CB MNCs can be EvE up to 7 days to yield viable and activated NK and NKT-like subsets that appear to be cytolytic based on the cell repertoire and could be utilized in the future as adoptive cellular immunotherapy post-unrelated CB transplantation.


Assuntos
Sangue Fetal/citologia , Imunoterapia Adotiva , Células Matadoras Naturais/imunologia , Monócitos/citologia , Células T Matadoras Naturais/imunologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular , Linhagem Celular Tumoral , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Criopreservação , Meios de Cultivo Condicionados/análise , Meios de Cultura Livres de Soro/farmacologia , Citocinas/biossíntese , Citocinas/genética , Citotoxicidade Imunológica , Humanos , Imunofenotipagem , Imunoterapia Adotiva/métodos , Recém-Nascido , Interferon gama/biossíntese , Interferon gama/genética , Interleucinas/biossíntese , Interleucinas/genética , Interleucinas/farmacologia , Células Matadoras Ativadas por Linfocina/citologia , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/citologia , Muromonab-CD3/farmacologia , Células T Matadoras Naturais/citologia , Receptores Imunológicos/biossíntese , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia
19.
Br J Haematol ; 144(1): 24-40, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19087093

RESUMO

Lymphoma is the most common malignancy among adolescents, accounting for >25% of newly diagnosed cancers in the 15-19 year age group. Hodgkin lymphoma (HL) accounts for the majority (two-thirds) of cases, while the remainder of patients have one of four subtypes of non-Hodgkin lymphoma (NHL): diffuse large B-cell lymphoma (DLBCL) including primary mediastinal B-cell lymphoma (PMBL), Burkitt lymphoma (BL), lymphoblastic lymphoma (LL) or anaplastic large cell lymphoma (ALCL). Epidemiology, histology, treatment and outcome differ between HL and NHL, as well as among the various subtypes of NHL. Adolescent lymphoma is particularly interesting because it often shares features with both childhood and adult lymphoma. As medical oncologists and paediatric oncologists often follow divergent treatment plans, disagreements may arise between practitioners as to how best treat the adolescent group. Additional complicating factors associated with the adolescent years, such as lack of insurance, issues pertaining to body image, and concerns about fertility, can also hinder prompt, appropriate medical management. This review details the complexities associated with the diagnosis and treatment of adolescent lymphoma and updates the state of the science, with particular emphasis on epidemiology, diagnosis, and proper management of HL and the various subtypes of NHL.


Assuntos
Doença de Hodgkin/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adolescente , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/terapia , Adulto Jovem
20.
Expert Opin Biol Ther ; 8(10): 1595-604, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18774926

RESUMO

Acute tumor lysis syndrome (TLS) is an oncologic emergency resulting in several metabolic derangements. Hyperuricemia and its associated complications are the most frequent manifestations of TLS. Crucial to the management is the prompt initiation of a hypouricemic agent such as rasburicase. An established dose of 0.2 mg/kg of rasburicase is effective at decreasing uric acid levels significantly in 4 h of administration and to undetectable levels in 48 h of initiation. The mean uric acid AUC is significantly lower for patients treated with rasburicase when compared to those receiving allopurinol. Rasburicase has demonstrated excellent tolerability and is potentially cost-effective in patients at high risk for TLS. Rasburicase is a safe and effective hypouricemic agent for both adults and children at high risk for TLS and for this reason should be considered the uricolytic agent of choice in these patients.


Assuntos
Antineoplásicos/uso terapêutico , Síndrome de Lise Tumoral/tratamento farmacológico , Urato Oxidase/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Ensaios Clínicos como Assunto , Humanos , Urato Oxidase/efeitos adversos , Urato Oxidase/economia
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