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1.
Acta Haematol ; 143(1): 40-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31315113

RESUMO

BACKGROUND: Outcomes for patients with peripheral T-cell lymphoma (PTCL) who fail to achieve complete response (CR) or relapse after front-line therapy are poor with lack of prospective outcomes data. OBJECTIVES: COMPLETE is a prospective registry of 499 patients enrolled at academic and community sites in the United States detailing patient demographics, treatment and outcomes for patients with aggressive T cell lymphomas. We report results for patients with primary refractory and relapsed disease. METHODS: Primary refractory disease was defined as an evaluable best response to initial treatment (induction ± maintenance or consolidation/transplant) other than CR, and included a partial response, progressive disease, or no response/stable disease. Relapsed disease was defined as an evaluable best response to initial treatment of CR, followed by disease progression at a later date, irrespective of time to progression. Patients were included in the analysis if initial treatment began within 30 days of enrollment and treatment duration was ≥4 days. RESULTS: Of 420 evaluable patients, 97 met the definition for primary refractory and 58 with relapsed disease. In the second-line setting, relapsed patients received single-agent therapies more often than refractory patients (52 vs. 28%; p = 0.01) and were more likely to receive single-agent regimens (74 vs. 53%; p = 0.03). The objective response rate to second-line therapy was higher in relapsed patients (61 vs. 40%; p = 0.04) as was the proportion achieving a CR (41 vs. 14%; p = 0.002). Further, relapsed patients had longer overall survival (OS) compared to refractory patients, with a median OS of 29.1 versus 12.3 months. CONCLUSIONS: Despite the availability of newer active single agents, refractory patients were less likely to receive these therapies and continue to have inferior outcomes compared to those with relapsed disease. PTCL in the real world remains an unmet medical need, and improvements in front-line therapies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Recidiva , Sistema de Registros , Falha de Tratamento
2.
Cancer ; 125(9): 1507-1517, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30694529

RESUMO

BACKGROUND: The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T-cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1. METHODS: Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis. RESULTS: Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty-three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow-up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced-stage disease or intermediate-to-high International Prognostic Index scores. ASCT significantly improved overall and progression-free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15-0.89). CONCLUSIONS: This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/terapia , Metástase Linfática , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
3.
J Natl Compr Canc Netw ; 16(2): 123-135, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29439173

RESUMO

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.


Assuntos
Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Gerenciamento Clínico , Humanos , Linfoma de Células T/etiologia
4.
Biol Blood Marrow Transplant ; 23(3): 529-532, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28013014

RESUMO

New-onset post-transplantation diabetes mellitus (PTDM) occurs commonly after allogeneic hematopoietic cell transplantation (HCT) and is associated with inferior survival. We hypothesize that PTDM and nonrelapse mortality (NRM) are related to IL-33/suppression of tumorigenicity 2 (ST2) signaling and that soluble ST2 (sST2) levels will predict PTDM diagnosis. sST2 was measured at engraftment and day +30 in 36 euglycemic HCT recipients followed prospectively for PTDM (cohort 1). Results were confirmed in a validation cohort of 26 patients without pre-existing diabetes analyzed retrospectively for PTDM (cohort 2). Twelve patients with established diabetes before HCT were analyzed in cohort 3. When compared with recipients without PTDM, patients developing PTDM (n = 24) from cohort 1 had elevated sST2 levels at engraftment (P = .02) and at day +30 (P < .01). Cohort 2 confirmed this finding at engraftment (P = .01). Cohort 3 patients with pretransplantation diabetes had higher sST2 at engraftment than patients maintaining euglycemia after HCT from cohort 2 (P = .03). Multivariate analysis of cohorts 1 and 2 showed high engraftment sST2 predicted increased PTDM and NRM risk, independent of conditioning and grades 3 to 4 acute graft-versus-host-disease. sST2 was elevated in PTDM, indicating a relationship between glucose homeostasis and the IL-33/ST2 axis after transplantation. Correction of metabolic complications may decrease sST2 and improve NRM.


Assuntos
Diabetes Mellitus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Transdução de Sinais , Adulto , Idoso , Glicemia/metabolismo , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Adulto Jovem
5.
Cancer ; 123(7): 1174-1183, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27911989

RESUMO

BACKGROUND: Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. METHODS: Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided. RESULTS: Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]). CONCLUSIONS: To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174-1183. © 2016 American Cancer Society.


Assuntos
Linfoma de Células T Periférico/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Feminino , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Prospectivos , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
6.
J Natl Compr Canc Netw ; 15(9): 1091-1102, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28874594

RESUMO

The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , História do Século XXI , Humanos
7.
Biol Blood Marrow Transplant ; 22(10): 1801-1807, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27377900

RESUMO

Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Bussulfano/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia de Células B/complicações , Leucemia de Células B/mortalidade , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Rituximab/uso terapêutico , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
8.
9.
J Natl Compr Canc Netw ; 13(10): 1240-79, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26483064

RESUMO

Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org.


Assuntos
Guias de Prática Clínica como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Fatores de Risco
10.
Blood ; 118(4): 1140-4, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21628416

RESUMO

B-cell activating factor (BAFF) single nucleotide polymorphisms (SNPs) are associated with autoimmune diseases. Because patients with classic and overlap chronic GVHD (cGVHD) have features of autoimmune diseases, we studied the association of recipient and/or donor BAFF SNPs with the phenotype of GVHD after allogeneic stem cell transplantation. Twenty tagSNPs of the BAFF gene were genotyped in 164 recipient/donor pairs. GVHD after day 100 occurred in 124 (76%) patients: acute GVHD (aGVHD) subtypes (n = 23), overlap GVHD (n = 29), and classic cGVHD (n = 72). In SNP analyses, 9 of the 20 tag SNPs were significant comparing classic/overlap cGVHD versus aGVHD subtypes/no GVHD. In multivariate analyses, 4 recipient BAFF SNPs (rs16972217 [odds ratio = 2.72, P = .004], rs7993590 [odds ratio = 2.35, P = .011], rs12428930 [odds ratio2.53, P = .008], and rs2893321 [odds ratio = 2.48, P = .009]) were independent predictors of GVHD subtypes, adjusted for conventional predictors of cGVHD. This study shows that genetic variation of BAFF modulates GVHD phenotype after allogeneic stem cell transplantation.


Assuntos
Fator Ativador de Células B/genética , Doença Enxerto-Hospedeiro/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Transplante Homólogo , Adulto Jovem
11.
Biol Blood Marrow Transplant ; 18(7): 1069-75, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22178694

RESUMO

Relapse remains a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Graft-versus-tumor effect is primarily mediated by donor T cells. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a critical inhibitor of T cell proliferation. Single nucleotide polymorphisms (SNPs) in CTLA-4 may affect immune responses. We hypothesized that CTLA-4 SNPs will be associated with disease control after allo-HCT. One hundred sixty-four adult patients with the availability of pretransplantation recipient and donor DNA samples were included in this analysis. Ten tagSNPs of the CTLA-4 gene were identified. Donor CTLA-4 SNP rs4553808 was associated with decreased relapse-free survival (RFS) (P = .019) and overall survival (OS) (P = .033). In multivariable analysis of an additive genetic model, genotype of CTLA-4 SNP rs4553808 was an independent risk factor for inferior RFS (hazard ratio [HR] = 1.73, 95% confidence interval [CI] 1.10-2.71, P = .017) and OS (HR = 1.84, 95% CI 1.13-3.0, P = .015). CTLA-4 SNPs can be used to identify high-risk patient subsets that may benefit from preemptive immunomodulation to decrease relapse rates and improve survival.


Assuntos
Antígeno CTLA-4/genética , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Antígeno CTLA-4/imunologia , Feminino , Efeito Enxerto vs Tumor/imunologia , Neoplasias Hematológicas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/imunologia , Fatores de Risco , Prevenção Secundária , Análise de Sobrevida , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
13.
J Natl Compr Canc Netw ; 10(11): 1412-45, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23138169

RESUMO

Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.


Assuntos
Infecções Bacterianas/prevenção & controle , Hospedeiro Imunocomprometido , Micoses/prevenção & controle , Neoplasias/complicações , Viroses/prevenção & controle , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/etiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Micoses/etiologia , Micoses/imunologia , Micoses/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neutropenia/induzido quimicamente , Neutropenia/complicações , Fatores de Risco , Viroses/etiologia , Viroses/imunologia , Viroses/terapia
15.
Cytotherapy ; 13(1): 78-82, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20586668

RESUMO

BACKGROUND AIMS: Previous studies have shown that rapid recovery of the absolute lymphocyte count (ALC) is associated with improved transplant outcomes after related and unrelated donor allogeneic stem cell transplantation (allo-SCT). No consistent association has been reported between lymphocyte recovery and transplant outcome after cord blood transplantation (CBT). METHODS: We reviewed the records of 40 consecutive CBT patients at our institution to determine the impact of lymphocyte recovery on transplant outcome. RESULTS: The majority of patients (83%) received CBT for hematologic malignancies. Patients with ALC ≥150/µL at 30 days post-CBT had decreased non-relapse mortality (NRM) (P = 0.011) and improved survival (P = 0.013) compared with ALC <150/µL. Patients with ALC <100/µL at 30 days post-CBT had a significantly higher rate of graft failure than those with ALC ≥100/µL (four of 10 versus one of 29; P = 0.011). ALC was positively correlated with the nucleated cell dose and inversely correlated with the patient's age. There was no relationship between disease risk, type of conditioning regimen, anti-thymocyte globulin and number of cord units on ALC recovery. CONCLUSIONS: Our results indicate that ALC 30 days post-CBT is a surrogate for engraftment, and that low ALC (<150/µL) identifies an 'at-risk' population of patients after CBT. Studies are needed to determine ways to increase ALC cell numbers post-CBT, including ex vivo-expanded natural killer cells using adoptive immunotherapy, which might improve outcome after CBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Linfócitos/imunologia , Adolescente , Adulto , Causas de Morte , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Contagem de Linfócitos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Sci Rep ; 10(1): 17536, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067482

RESUMO

Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities.


Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Oncologia/história , Neoplasias/tratamento farmacológico , Editoração/tendências , Análise de Rede Social , Algoritmos , Autoria , Feminino , História do Século XX , História do Século XXI , Humanos , Masculino , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Pesquisadores
17.
Biol Blood Marrow Transplant ; 15(10): 1288-95, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19747637

RESUMO

The National Institutes of Health (NIH) classification of graft-versus-host disease (GVHD) is a significant improvement over prior classifications, and has prognostic implications. We hypothesized that the NIH classification of GVHD would predict the survival of patients with GVHD treated with extracorporeal photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD treated with ECP were studied. The 3-year overall survival (OS) was 36% (95% confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to 3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for patients with classic cGVHD (median survival, not reached) compared to overlap GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed, recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate analyses, significant predictors of survival after ECP included GVHD subtype, bilirubin, platelet count, and steroid dose. In multivariate analyses overlap plus classic cGVHD was an independent prognostic feature predictive of superior survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests that NIH classification can predict outcome after ECP for steroid refractory/dependent GVHD.


Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Fotoferese , Doença Aguda , Adulto , Idoso , Bilirrubina/sangue , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/classificação , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
19.
Ocul Oncol Pathol ; 5(4): 245-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31367585

RESUMO

Mantle cell lymphoma (MCL) is an uncommon form of non-Hodgkin lymphoma predominantly affecting male individuals of advanced age. Approximately 1-9% of cases of lymphoma affecting the orbital and ocular adnexal regions are attributed to MCL. We describe the case of a 65-year-old man with a 24-year history of MCL with initial remission followed by multiple relapses who presented with acute-onset binocular diplopia and proptosis of the left eye. Subsequent imaging demonstrated a new left superior orbital mass. Biopsy of the mass revealed two clonally related, yet distinct cellular components demonstrating the classical mantle cell morphology and large cells that appeared to have transformed to the blastoid variant of MCL. Transformation of classical MCL to the blastoid variant of MCL is rare, with few reports in the literature. The blastoid variant of MCL tends to be aggressive and associated with a poor prognosis. The case we describe represents perhaps the first report of MCL transformation observed in the orbit.

20.
Leuk Lymphoma ; 60(12): 2880-2889, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31184237

RESUMO

Primary central nervous system lymphoma (PCNSL) patients have a poorer prognosis than systemic lymphoma. Gain-of-function MYD88 c.794T > C (p. L265P) mutation and programed cell death-1 (PD-1) pathway alterations are potential targetable pathways. Our study objective was to determine the clinicopathologic correlates of MYD88 mutation and PD-1 alterations in PCNSL and the impact of Epstein-Barr virus (EBV) infection. We studied 53 cases including 13 EBV-associated (EBVpos) PCNSL, 49% harbored MYD88 mutation, none seen in EBVpos PCNSL. MYD88 protein expression did not correlate with MYD88 mutation. T-cell and macrophage infiltration was common. All PD-L1-positive tumors were EBVpos. Two PD-L1 positive tumors showed 9p24.1/PD-L1 locus alterations by Fluorescence In Situ Hybridization. T cells and macrophages expressed PD-1 and/or PD-L1 in 98% and 83% cases, respectively. MYD88 mutation or protein expression and PD-1 or PD-L1 expression did not predict outcome. We hypothesize that EBVpos PCNSL has a distinct activation mechanism, independent of genetic alterations.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Mutação , Fator 88 de Diferenciação Mieloide/genética , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Alelos , Substituição de Aminoácidos , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/metabolismo
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