RESUMO
Chemoimmunotherapy followed by consolidative high-dose therapy with autologous stem cell rescue was a standard upfront treatment for fit patients with mantle cell lymphoma (MCL) in first remission; however, treatment paradigms are evolving in the era of novel therapies. Lenalidomide is an immunomodulatory agent with known efficacy in treating MCL. We conducted a single-center, investigator-initiated, phase II study of immunochemotherapy incorporating lenalidomide, without autologous stem cell transplant consolidation, enriching for patients with high-risk MCL (clinicaltrials gov. Identifier: NCT02633137). Patients received four cycles of lenalidomide-R-CHOP, two cycles of R-HiDAC, and six cycles of R-lenalidomide. The primary endpoint was rate of 3-year progression-free survival. We measured measurable residual disease (MRD) using a next-generation sequencing-based assay after each phase of treatment and at 6 months following end-oftreatment. We enrolled 49 patients of which 47 were response evaluable. By intent-to-treat, rates of overall and complete response were equivalent at 88% (43/49), one patient with stable disease, and two patients had disease progression during study; 3-year progression-free survival was 63% (primary endpoint not met) and differed by TP53 status (78% wild-type vs. 38% ALT; P=0.043). MRD status was prognostic and predicted long-term outcomes following R-HiDAC and at 6 months following end-of-treatment. In a high-dose therapy-sparing, intensive approach, we achieved favorable outcomes in TP53- wild-type MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL.
Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Lenalidomida/uso terapêutico , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Prognóstico , ImunoterapiaRESUMO
Data describing outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with secondary central nervous system (SCNS) involvement of mantle cell lymphoma (MCL) are limited. We identified 10 patients with MCL and SCNS involvement treated with anti-CD19 CAR T-cell therapy at three US academic centres. Frequent objective responses were observed in the CNS (86%) and systemically (90%), and the 1-year progression-free survival was 47%. Seven patients developed immune-effector-cell-associated-neurotoxicity-syndrome (n = 2 Grade 1, n = 5 Grade 3). Our results suggest that anti-CD19 CAR T-cell therapy in this setting is feasible and additional data regarding neurotoxicity in this population may be warranted.
Assuntos
Linfoma de Célula do Manto , Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Adulto , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfoma de Célula do Manto/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfócitos T , Resultado do Tratamento , Antígenos CD19 , Sistema Nervoso Central , Síndromes Neurotóxicas/tratamento farmacológico , Terapia Baseada em Transplante de Células e TecidosRESUMO
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
Assuntos
Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Humanos , Linfócitos T/patologia , Estudos Retrospectivos , Células Matadoras Naturais/patologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/terapiaRESUMO
Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD- remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD- after induction or later MRD- after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco , Indução de Remissão , Transplante Homólogo , Neoplasia Residual/genéticaRESUMO
OPINION STATEMENT: Adult T-cell leukemia/lymphoma (ATL) is a rare, aggressive subtype of peripheral T-cell lymphoma developing after many years of chronic, asymptomatic infection with the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 is endemic to certain geographic areas of the world, and primary infection generally occurs in infancy through mother-to-child transmission via breastfeeding. In less than 5% of infected individuals, a decades-long pathogenic process culminates in the development of ATL. Aggressive subtypes of ATL are life-threatening and challenging to treat, with median overall survival typically less than 1 year in the absence of allogeneic hematopoietic cell transplantation (alloHCT). Owing to the rarity of this illness, prospective large-scale clinical trials have been challenging to perform, and treatment recommendations are largely founded upon limited evidence. Herein, we review the current therapeutic options for ATL, providing a broad literature overview of the foremost clinical trials and reports of this disease. We emphasize our own treatment paradigm, which is broadly based upon disease subtype, patient fitness, and intent to perform alloHCT. Finally, we highlight recent advances in understanding ATL disease biology and important ongoing clinical trials that we foresee as informative and potentially practice-changing.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Feminino , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/terapia , Estudos Prospectivos , Transmissão Vertical de Doenças InfecciosasRESUMO
ABSTRACT: Primary cutaneous gamma-delta T-cell lymphoma (PCGDTL) is a rare and diagnostically challenging primary skin lymphoma. We present a case of a 78-year-old otherwise healthy man who developed nonhealing nodules on his right posterior calf. Initial biopsy showed a dense, atypical, lymphoid infiltrate with gamma-delta and cytotoxic T-cell immunophenotypes. The diagnosis of PCGDTL was rendered; however, concurrent flow cytometry revealed expression of aberrant B-cell markers, including CD19 and cytoplasmic CD79a. Subsequent immunohistochemical studies corroborated this result. We report the extremely rare phenomenon of aberrant B-cell marker expression in PCGDTL, the first formally reported case to our knowledge.
Assuntos
Linfoma Cutâneo de Células T , Linfoma de Células T , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Neoplasias Cutâneas/patologia , Biópsia , Linfoma de Células T/patologia , Linfoma Cutâneo de Células T/patologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismoRESUMO
The peripheral T-cell lymphomas (PTCLs) are a notoriously diverse family of non-Hodgkin lymphomas with generally aggressive biology. Clinical management is challenging given a largely inadequate literature base comprised of few randomized trials and heterogeneous observational reports. Herein, we provide an account of our practice in the treatment of the 3 most common nodal PTCLs: PTCL, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma (ALCL). In the up-front setting, we employ anthracycline-based induction, with the incorporation of brentuximab vedotin for all those with ALCL and consideration in those with other CD30-expressing PTCLs based on improved progression-free and overall survival in the absence of additional toxicity in the ECHELON-2 trial. We strongly consider high-dose therapy with autologous stem cell rescue in first complete remission. In the relapsed or refractory (R/R) setting, we often look to clinical trials or choose from 4 FDA-approved single agents-belinostat, brentuximab vedotin, romidepsin, and pralatrexate-based on tumor phenotype and side-effect profiles. Our goal in the R/R setting is achievement of complete remission followed by allogeneic transplant with curative intent in appropriate candidates or long-term disease control in others. Numerous investigational agents are advancing through trials and have potential to alter standards of care in the near future.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Transplante AutólogoRESUMO
PURPOSE: The value of testing for folate deficiency has been scrutinized recently given low prevalence of deficiency with widespread dietary fortification. Numerous studies have shown folate testing to be low yield overall. However, the value of such testing in the inpatient cancer population has not been defined. METHODS: We queried all folate tests performed during 2017 at our center on admitted cancer patients. We used diagnosis codes and manual chart review to assess risk factors for folate deficiency. Descriptive statistics were used to summarize characteristics of patients undergoing folate testing, the frequency of vitamin B12 co-testing, and repeat folate testing. Fisher's exact test was used to compare the proportion of deficient vs. not deficient tests based on the presence of risk factors. A Cox proportional hazards model was fit to examine the association between folate deficiency and survival. RESULTS: In total, 937 patients had 1065 tests performed during 2017. Among all tests, 7.0% indicated folate deficiency. In patients who underwent two folate tests in a single hospitalization, 89% were deficient neither instance. Risk factors for folate deficiency were equally common in instances with deficient compared with replete testing (25.3 vs. 20.4%, P = 0.334). Folate deficiency was associated with higher risk for death (HR 1.49, 95% CI 1.10-2.03, P = 0.01). CONCLUSION: Folate deficiency was present in 7% of hospitalized cancer patients and associated with shorter overall survival. Repeat testing in the same patient over time was low yield. Traditional risk factors for folate deficiency do not appear to apply in this patient population.
Assuntos
Deficiência de Ácido Fólico/diagnóstico , Ácido Fólico/sangue , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Dieta , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/mortalidade , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Vitamina B 12/análiseAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Lenalidomida , Linfoma de Célula do Manto , Neoplasia Residual , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/terapia , Linfoma de Célula do Manto/patologia , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagem , Neoplasia Residual/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/administração & dosagem , Imunoterapia/métodosRESUMO
Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and difficult to standardize. Here we demonstrate that loss of plasmacytoid dendritic cell differentiation after 7+3 induction in AML is highly specific for measurable residual disease positivity (specificity 97.4%) in a uniformly treated patient cohort. Moreover, loss of plasmacytoid dendritic cell differentiation as determined by a blast-to-plasmacytoid dendritic cell ratio >10 was strongly associated with inferior overall and relapse-free survival (RFS) [Hazard ratio 2.79, 95% confidence interval (95%CI): 0.98-7.97; P=0.077) and 3.83 (95%CI: 1.51-9.74; P=0.007), respectively), which is similar in magnitude to measurable residual disease positivity. Importantly, measurable residual disease positive patients who reconstituted plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) showed a higher rate of measurable residual disease clearance at later pre-transplant time points compared to patients with loss of plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) (6 of 12, 50% vs 2 of 18, 11%; P=0.03). Furthermore pre-transplant plasmacytoid dendritic cell recovery was associated with superior outcome in measurable residual disease positive patients. Our study provides a novel, simple, broadly applicable, and quantitative multi-color flow cytometry approach to risk stratification in AML.
Assuntos
Células Dendríticas/patologia , Leucemia Mieloide Aguda/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual/mortalidade , Adulto , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Condicionamento Pré-Transplante , Transplante Autólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Masculino , Pessoa de Meia-Idade , Feminino , Citarabina/administração & dosagem , Citarabina/farmacocinética , Citarabina/uso terapêutico , Carmustina/administração & dosagem , Carmustina/farmacocinética , Carmustina/uso terapêutico , Adulto , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Melfalan/farmacocinética , IdosoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mutação com Ganho de Função , Genes ras , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Alelos , Medula Óssea/patologia , Células Clonais , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Recidiva , Indução de Remissão , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Predicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (< 3 months) and long (> 1 year) LEs. METHODS: The records of 862 patients with metastatic cancer receiving palliative RT at the Dana-Farber/Brigham and Women's Cancer Center between June 2008 and July 2011 were retrospectively reviewed. Cox proportional hazards models were used to evaluate established and potential clinical predictors of LE to construct a model predicting LE of < 3 months and > 1 year. RESULTS: The median survival was 5.6 months. On multivariate analysis, factors found to be significantly associated with a shorter LE were cancer type (lung and other vs breast and prostate), older age (> 60 years vs ≤ 60 years), liver metastases, Eastern Cooperative Oncology Group performance status (2-4 vs 0-1), hospitalizations within 3 months before palliative RT (0 vs ≥ 1), and prior palliative chemotherapy courses (≥ 2 vs 0-1). Patients were divided into 3 groups with distinct median survivals: group A (those with 0-1 risk factors), 19.9 months (95% confidence interval [95% CI, 13.9 months-31.1 months]); group B (those with 2-4 risk factors), 5.0 months (95% CI, 4.3 months -5.6 months); and group C (those with 5-6 risk factors), 1.7 months (95% CI, 1.2 months-2.1 months). CONCLUSIONS: The TEACHH model (type of cancer, Eastern Cooperative Oncology Group performance status, age, prior palliative chemotherapy, prior hospitalizations, and hepatic metastases) divides patients receiving palliative RT into 3 distinct LE groups at clinically informative extremes of the LE spectrum. It holds promise to assist radiation oncologists in tailoring palliative therapies to a patient's LE.
Assuntos
Expectativa de Vida , Modelos Estatísticos , Neoplasias/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets next-generation sequencing panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with an increased risk of progression (by multivariate analysis) included advanced-stage disease and bone marrow involvement. The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations and TP53/17p deletions. PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months for PTCL with a TP53 mutation (n = 21) vs 10.5 months for PTCL without a TP53 mutation (n = 111). No TP53 aberrancy correlated with inferior overall survival (OS). Although rare (n = 9), CDKN2A-deleted PTCL correlated with inferior OS, with a median of 17.6 months vs 56.7 months for patients without CDKN2A deletions. This retrospective study suggests that patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.
Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , MutaçãoRESUMO
Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin B-cell lymphoma that has historically been difficult to define, though is now formally recognized by the World Health Organization Classification. To better characterize the clinical outcomes of patients with NMZL, we reviewed a sequential cohort of 187 patients with NMZL to describe baseline characteristics, survival outcomes, and time-to-event data. Initial management strategies were classified into five categories: observation, radiation, anti-CD20 monoclonal antibody therapy, chemoimmunotherapy, or other. Baseline Follicular Lymphoma International Prognostic Index scores were calculated to evaluate prognosis. A total of 187 patients were analyzed. The five-year overall survival was 91% (95% confidence interval [CI], 87-95), with a median follow-up time of 71 months (range, 8-253) among survivors. A total of 139 patients received active treatment at any point, with a median follow-up time of 56 months (range, 13-253) among survivors who were never treated. The probability of remaining untreated at five years was 25% (95% CI, 19-33). For those initially observed, the median time to active treatment was 72 months (95% CI, 49-not reached). For those who received at least one active treatment, the cumulative incidence of receiving a second active treatment at 60 months was 37%. Transformation to large B-cell lymphoma was rare, with a cumulative incidence of 15% at 10 years. In summary, our series is a large cohort of uniformly diagnosed NMZL with detailed analyses of survival and time to event analyses. We showed that NMZL commonly presents as an indolent lymphoma for which initial observation is often a reasonable strategy.
Assuntos
Antineoplásicos , Linfoma de Zona Marginal Tipo Células B , Humanos , Estudos Retrospectivos , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Prognóstico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêuticoRESUMO
Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization and International Consensus classifications of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as 1 of the diagnostic criteria for AML, AML-MR, based largely on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined in the clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations into the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed patients with AML treated at the Memorial Sloan Kettering Cancer Center, we show that ontogeny assignments based on the database registry lack accuracy. MR gene mutations are frequently observed in de novo AML. Among the MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in the univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also helped stratify the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny, and questions the current classification and risk stratification of AML with MR gene mutations.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Prognóstico , Fatores de RiscoRESUMO
The arcuate fasciculus (AF) is believed to be fundamental to the neural circuitry behind many important cognitive processes. Connecting Wernicke's and Broca's area, these fibers are thought to be especially important for repetition. In this case study we present evidence from a patient that set doubt on these assumptions. We present structural imaging, diffusion tensor imaging, and language data on a patient with a large left-sided stroke and severely damaged left AF who showed intact word repetition and relatively intact sentence repetition performance. Specifically, his sentence repetition is more fluent and grammatical, with less hesitation than spontaneous speech, and with rare omissions only during the longest sentences. These results challenge classical theories that maintain the left AF is the dominant language processing pathway or mechanism for repetition.
Assuntos
Afasia/diagnóstico , Lateralidade Funcional , Idioma , Vias Neurais/patologia , Acidente Vascular Cerebral/complicações , Comportamento Verbal , Afasia/etiologia , Afasia/patologia , Imagem de Tensor de Difusão , Lobo Frontal , Neuroimagem Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/patologia , Lobo Temporal , Aprendizagem VerbalRESUMO
Mantle cell lymphoma (MCL) is a morphologically and phenotypically heterogeneous subtype of non-Hodgkin lymphoma, and has historically been associated with poor outcomes. However, recent advances in our understanding of this disease have yielded new targeted and immune-based therapies with promising activity. Immune-based therapies such as monoclonal antibodies, immunomodulators, and CAR T cells have significantly improved outcomes and are now standard of care in MCL. In this review, we describe our current understanding of the immune microenvironment of MCL, discuss current immunotherapeutic approaches, and highlight promising novel immune-based therapies and combination therapies that may further improve outcomes for patients with MCL.