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1.
Biomarkers ; 25(1): 69-75, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31752540

RESUMO

Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL.Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens.Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01).Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.

2.
Blood ; 135(4): 274-286, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31738823

RESUMO

Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma-related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

3.
Lab Med ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834933

RESUMO

BACKGROUND: Differences between follicular lymphoma (FL) and diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) by flow cytometry are underexplored. METHODS: We retrospectively assessed flow cytometry results from 191 consecutive lymph node biopsies diagnosed with FL or DLBCL/HGBL. RESULTS: The only parameters that differed between the 2 groups in the derivation cohort were forward scatter and side scatter (P < 10-6; area under the curve [AUC], 0.75-0.8) and %CD23 (P = .004; area under the receiver characteristic operating curve, 0.64). However, since light scatter characteristics did not distinguish between grade 3 FL and DLBCL/HGBL, we set out to develop a model with high sensitivity for the exclusion of the latter. Several models, including FS and %CD23, were tested, and 2 models showed a sensitivity of >0.90, with negative predictive values of ≥0.95, albeit with low specificity (0.45 to 0.57). CONCLUSION: Two simple models enable the exclusion of DLBCL/HGBL with a high degree of confidence.

4.
Eur J Haematol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769545

RESUMO

OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.

5.
Front Immunol ; 10: 2464, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681334

RESUMO

The administration of a high fat content diet is an accelerating factor for metabolic syndrome, impaired glucose tolerance, and early type 2 diabetes. The present study aims to assess the impact of a high fat diet on tuberculosis progression and microbiota composition in an experimental animal model using a C3HeB/FeJ mouse strain submitted to single or multiple consecutive aerosol infections. These models allowed us to study the protection induced by Bacillus Calmette-Guérin vaccination as well as by the natural immunity induced by chemotherapy after a low dose Mycobacterium tuberculosis infection. Our results show that a high fat diet is able to trigger a pro-inflammatory response, which results in a faster progression toward active tuberculosis and an impaired protective effect of BCG vaccination, which is not the case for natural immunity. This may be related to dysbiosis and a reduction in the Firmicutes/Bacteroidetes ratio in the gut microbiota caused by a decrease in the abundance of the Porphyromonadaceae family and, in particular, the Barnesiella genus. It should also be noted that a high fat diet is also related to an increase in the genera Alistipes, Parasuterella, Mucispirillum, and Akkermansia, which have previously been related to dysbiotic processes. As diabetes mellitus type 2 is a risk factor for developing tuberculosis, these findings may prove useful in the search for new prophylactic strategies for this population subset.

6.
Nat Commun ; 10(1): 4739, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628331

RESUMO

HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Memória Imunológica/imunologia , Adulto , Idoso , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Reservatórios de Doenças/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/virologia , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Carga Viral/imunologia
7.
Hematol Oncol ; 37(5): 564-568, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31475375

RESUMO

Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.


Assuntos
Biomarcadores Tumorais/genética , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Idoso , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
8.
Oncoimmunology ; 8(8): 1602460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413912

RESUMO

Intravesical Bacille Calmette-Guérin (BCG) remains the most effective treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), unfortunately there is no validated biomarker to predict clinical outcome. Here we tried to explore the possibility that a combination of the density of peritumoral infiltrating cells (Th1, Th2 and PD-L1) and the composition of peripheral immune cells (neutrophil and lymphocyte counts) could generate a more reliable prognostic biomarker. Twenty-two patients with high-risk NMIBC treated with BCG (10 BCG nonresponders and 12 BCG responders) were selected. BCG responders had significantly lower level of peritumoral T-bet+ cells with an associated higher GATA-3+/T-bet+ ratio (p = 0.04, p = 0.02, respectively). Furthermore, the immune polarization in tissue (GATA-3+/T-bet+ ratio) adjusted for the systemic inflammation (neutrophil-to-lymphocyte ratio) showed a significantly higher association with the BCG response (p = 0.004). A survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with a lower T-bet+/Lymphocyte ratio and higher GTR/NLR (p = 0.01). No association was observed between peritumoral PD-L1+ expression and the BCG response. In conclusion, alterations in overall immune function, both local and systemic, may influence the therapeutic response to BCG, therefore a combined analysis of tumoral (Th2/Th1 ratio) and peripheral (NLR) immune composition prior to treatment may be a promising approach to predict the BCG response in high-risk NMIBC patients.

10.
Front Immunol ; 10: 825, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114569

RESUMO

Antigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies.

11.
Leuk Lymphoma ; 60(10): 2524-2531, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30942640

RESUMO

Short responses to immunochemotherapy predict for an inferior OS in follicular lymphoma. We set out to determine whether this is also the case in marginal zone lymphoma. A group of 139 marginal zone lymphoma (MZL) patients treated with front-line immuno- or immunochemotherapy (I/ICT) were categorized into I/ICT-refractory (non-response or relapse/progression within six months of treatment response assessment) or I/ICT-sensitive. Twenty-three patients (17%) were refractory. Refractory patients had inferior OS (4-yr probabilities of 57% vs. 83%, p = .0003) as did those with beta2-microglobulin (B2M)>3 mg/L (4-yr probabilities of 80% vs. 100%, p = .0029). On multivariable analysis they both showed a borderline significant correlation with OS (p = .06 and .07, respectively). B2M > 3 mg/L was also an adverse prognostic factor for progression-free survival in both univariable (4-yr probability of 61% vs. 83%, p = .02) and multivariable analysis (HR 2.9, p = .02). In conclusion, B2M and refractoriness to I/ICT may identify patients with MZL at higher risk of inferior survival.

13.
Clin Infect Dis ; 68(5): 834-843, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29982484

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. METHODS: EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. RESULTS: HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P < .001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P < .001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67-0.96). CONCLUSIONS: Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development.

14.
Front Immunol ; 9: 798, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29740435

RESUMO

An excessive, non-productive host-immune response is detrimental in active, chronic tuberculosis (TB) disease as it typically leads to tissue damage. Given their anti-inflammatory effect, non-steroidal anti-inflammatory drugs can potentially attenuate excessive inflammation in active TB disease. As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (LDA) (3 mg/kg/day), either alone or in combination with common anti-TB treatment or BCG vaccination, on disease outcome in an experimental murine model of active TB. Survival rate, bacillary load (BL) in lungs, and lung pathology were measured. The possible mechanism of action of LDA on the host's immune response was also evaluated by measuring levels of CD5L/AIM, selected cytokines/chemokines and other inflammatory markers in serum and lung tissue. LDA increased survival, had anti-inflammatory effects, reduced lung pathology, and decreased bacillary load in late-stage TB disease. Moreover, in combination with common anti-TB treatment, LDA enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of LDA at both a local and a systemic level. Our results showed a systemic decrease in neutrophilic recruitment, decreased levels of acute-phase reaction cytokines (IL-6, IL-1ß, and TNF-α) at late stage and a delay in the decrease in T cell response (in terms of IFN-γ, IL-2, and IL-10 serum levels) that occurs during the course of Mycobacterium tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, LDA may be beneficial as an adjunct to standard anti-TB treatment in the later stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Tuberculose/patologia , Animais , Modelos Animais de Doenças , Camundongos
15.
Med. clín (Ed. impr.) ; 149(8): 339-342, oct. 2017. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-167659

RESUMO

Antecedentes y objetivo: Los linfomas con reordenamiento de MYC (MYC-R) diferentes al linfoma de Burkitt (LB) son muy agresivos, con un pronóstico desfavorable cuando se tratan con regímenes estándar. El objetivo del estudio fue investigar las características y el resultado de una serie de linfomas MYC-R, comparando los resultados del tratamiento de los regímenes basados en R-CHOP y un régimen intensivo específico para LB (BURKIMAB). Pacientes y métodos: Estudio retrospectivo de pacientes diagnosticados de MYC-R. Se evaluaron las translocaciones de MYC, BCL2 y BCL6 mediante hibridación in situ fluorescente. Se trató a los pacientes, bien con inmunoquimioterapia basada en R-CHOP, bien con el régimen tipo Burkitt, BURKIMAB. Resultados: Se estudiaron 34 casos de linfomas MYC-R: 21 tratados con R-CHOP y 13 tratados con BURKIMAB. No se produjeron diferencias en cuanto a tasa de RC; 45% (9/20) para R-CHOP y 42% (5/12) para BURKIMAB (p=0,99). Aunque la supervivencia global (SG) y la supervivencia libre de progresión (SLP) de los pacientes tratados con BURKIMAB fueron mejores que las de los pacientes tratados con R-CHOP (SG a 3 años: 46 frente a 24%; SLP a 3 años: 46 frente a 10%), las diferencias no fueron estadísticamente significativas. Conclusión: Los linfomas MYC-R muestran resultados desfavorables, aun cuando se tratan con inmunoquimioterapia intensiva para LB (AU)


Background and objective: MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). Patients and methods: Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB. Results: Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (P=.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant. Conclusion: MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL (AU)


Assuntos
Humanos , Linfoma de Burkitt/tratamento farmacológico , Genes myc , Antineoplásicos/uso terapêutico , Rearranjo Gênico , Estudos Retrospectivos , Resultado do Tratamento , Conduta do Tratamento Medicamentoso
16.
Matern Child Nutr ; 13 Suppl 12017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28960875

RESUMO

Realistic planning for a nutrition intervention is a critical component of implementation, yet effective approaches have been poorly documented. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," 3 working groups were formed to summarize experiences and lessons across countries regarding micronutrient powders (MNP) interventions for young children. This paper focuses on programmatic experiences in the planning stages of an MNP intervention, encompassing assessment, enabling environment and adaptation, as well as considerations for supply. Methods included a review of published and grey literature, key informant interviews, and deliberations throughout the consultation process. We found that assessments helped justify adopting an MNP intervention, but these assessments were often limited by their narrow scope and inadequate data. Establishing coordinating bodies and integrating MNP into existing policies and programmes have helped foster an enabling environment and support programme stability. Formative research and pilots have been used to adapt MNP interventions to specific contexts, but they have been insufficient to inform scale-up. In terms of supply, most countries have opted to procure MNP through international suppliers, but this still requires understanding and navigating the local regulatory environment at the earliest stages of an intervention. Overall, these findings indicate that although some key planning and supply activities are generally undertaken, improvements are needed to plan for effective scale-up. Much still needs to be learned on MNP planning, and we propose a set of research questions that require further investigation.


Assuntos
Anemia Ferropriva/prevenção & controle , Anemia/prevenção & controle , Planejamento em Saúde , Micronutrientes/administração & dosagem , Avaliação de Programas e Projetos de Saúde , Suplementos Nutricionais , Assistência Alimentar/organização & administração , Assistência Alimentar/estatística & dados numéricos , Alimentos Fortificados , Implementação de Plano de Saúde , Planejamento em Saúde/métodos , Promoção da Saúde , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Micronutrientes/deficiência , Micronutrientes/provisão & distribução , Pobreza , Pós , Estados Unidos , United States Agency for International Development
17.
Med Clin (Barc) ; 149(8): 339-342, 2017 Oct 23.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28648593

RESUMO

BACKGROUND AND OBJECTIVE: MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). PATIENTS AND METHODS: Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB. RESULTS: Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (P=.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant. CONCLUSION: MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Genes myc/genética , Fatores Imunológicos/uso terapêutico , Linfoma/tratamento farmacológico , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Linfoma/genética , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico
18.
AIDS ; 31(10): 1445-1449, 2017 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-28574963

RESUMO

OBJECTIVE: Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. DESIGN AND METHODS: We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. RESULTS: A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. CONCLUSION: Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.


Assuntos
Antineoplásicos/uso terapêutico , Infecções por HIV/complicações , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
Leuk Res ; 58: 98-101, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28521176

RESUMO

Nephrotoxicity is a well-known side effect of platinum-based chemotherapy. We retrospectively assessed the incidence and prognostic impact of nephrotoxicity with ESHAP rescue chemotherapy in 74 lymphoma patients (61 aggressive lymphomas). A higher incidence of nephrotoxicity (estimated glomerular filtration rate <60mL/min) was found when ESHAP was administred on an outpatient vs. inpatient basis (14/39 vs. 4/35). Patients submitted to ASCT with renal failure had a lower overall survival (OS) than those with normal renal function (2-yr OS probability [95%CI]: 88% [77%-99%] vs. 50% [22%-78%]). Outpatient administration of ESHAP may not be optimal for all patients and the impact of ESHAP-induced renal failure on ASCT outcomes in lymphoma needs to be assessed in prospective studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Linfoma/tratamento farmacológico , Terapia de Salvação/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
20.
Sci Rep ; 7: 46707, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28429796

RESUMO

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

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