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1.
Blood Adv ; 4(2): 253-262, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31945157

RESUMO

There is a paucity of data regarding outcomes and response to standard therapy in patients with limited-stage (LS) agressive B-cell lymphoma (LS-ABCL) who harbor MYC rearrangement (MYC-R) with or without BCL2 and/or BCL6 rearrangements. We conducted a multicenter retrospective study of MYC-R LS-ABCL patients who received either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or more intensive immunochemotherapy (IIC) plus or minus consolidative involved-field radiation therapy (IFRT). One hundred four patients from 15 academic centers were included. Forty four patients (42%) received R-CHOP, of whom 52% had IFRT. Sixty patients (58%) received IIC, of whom 40% had IFRT. Overall response rate was 91% (84% complete response [CR]; 7% partial response). Patients with double-hit lymphoma (DHL; n = 40) had a lower CR rate compared with patients with MYC-R only (75% vs 98%; P = .003). CR rate was higher in the IFRT vs no-IFRT group (98% vs 72%; P < .001). Median follow-up was 3.2 years; 2-year progression-free survival (PFS) and overal survival (OS) were 78% and 86% for the entire cohort, and 74% and 81% for the DHL patients, respectively. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort and in DHL patients. Our data provide a historical benchmark for MYC-R LS-ABCL and LS-DHL patients and show that outcomes for this population may be better than previously recognized. There was no benefit of using IIC over R-CHOP in patients with MYC-R LS-ABCL and LS-DHL.

3.
Clin Lymphoma Myeloma Leuk ; 19(12): 751-757, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648957

RESUMO

Adoptive cellular immunotherapy with anti CD19 chimeric antigen receptor (CAR)-T cell has changed the treatment landscape in relapsed/refractory B cell lymphomas. They have emerged as effective therapy in patients with multiple relapsed/refractory disease, capable of sustaining durable remissions. Two CAR-T cell products (axicabtagene ciloleucel and tisagenlecleucel) are currently approved by the United States Food and Drug Administration. A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon. CAR-T cell-related toxicities, including infections, cytokine release syndrome, and neurotoxicity are potential complications of therapy. With increasing use of CAR-T cells, the mechanism of toxicities and mitigation strategies needs to be developed. Additionally, reasons for CAR-T cell failure and progression following this therapy needs to be further studied. We describe the recent developments in this field, with emphasis on the complications of therapy and factors contributing to toxicities, efficacy, and resistance. We also describe the ongoing research in this field and the newer CAR-T cell constructs that are being developed to counter the challenges that have been identified in this field.

4.
J Natl Compr Canc Netw ; 17(6): 650-661, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31200358

RESUMO

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin's lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

5.
Sci Transl Med ; 11(497)2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217338

RESUMO

The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by immunoglobulin µ (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative analysis of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on immunoglobulin (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-negative constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysis-targeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting immunoglobulin signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease.

6.
Oncology (Williston Park) ; 33(5): 192-8, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31095720

RESUMO

Hodgkin lymphoma is a highly curable malignancy, with an excellent prognosis. However, around 10% to 25% of patients will have primary refractory or relapsed disease, despite using risk-adapted strategies. The standard of care for patients with relapsed/refractory Hodgkin lymphoma has been cytoreduction using salvage chemotherapy, followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT). Studies have shown that AHSCT produces a durable response rate of 50%, and that patients achieve a complete response with salvage chemotherapy. The outcomes for patients who do not respond to salvage chemotherapy or relapse after an AHSCT have been poor, with a median survival of 25 months. However, with the approval of novel agents over the last decade, the outcomes for patients with relapsed/refractory Hodgkin lymphoma have improved significantly. In this article, we present a case of a patient with relapsed Hodgkin lymphoma who responded to salvage chemotherapy incorporating brentuximab vedotin, a novel agent.

7.
Future Oncol ; 15(18): 2113-2124, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31144521

RESUMO

Aim: To examine whether the center type and socioeconomic factors significantly impact 1-month mortality and overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL). Methods: National Cancer Database (NCDB) was used to identify patients diagnosed with diffuse large B-cell lymphoma from 2006 to 2012 (postrituximab era). Results: Among 185,183 patients, 33% were treated at academic centers. The receipt of therapy at larger volume centers was associated with improved 1-month mortality. Academic centers had better OS than nonacademic centers in univariable analysis. Younger age, private insurance, lower Charlson comorbidity score and lower lymphoma stage were associated with improved 1-month mortality and OS. Conclusion: The receipt of therapy at larger volume centers and socioeconomic factors were associated with improved survival.


Assuntos
Instalações de Saúde , Linfoma Difuso de Grandes Células B/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Feminino , Instalações de Saúde/classificação , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Estudos Retrospectivos , Fatores Socioeconômicos , Estados Unidos/epidemiologia
9.
Leuk Lymphoma ; 60(9): 2255-2263, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30848966

RESUMO

Mantle cell lymphoma (MCL) is a rare cancer with diverse management options. Although clinical practice guidelines have become ubiquitous across medicine, the utility of guidelines for MCL management is limited by provider awareness and the lack of a definitive standard of care. We sought to determine whether expert recommendations, delivered as an online decision support tool, impacted practitioners' therapeutic decisions with MCL. Participants were more likely than the experts to select aggressive regimens for both newly diagnosed and relapsed/refractory MCL. After seeing the expert recommendations, participants revealed that the expert opinion impacted their treatment choices in 103 of 365 clinical scenarios, suggesting that online decision support tools may increase the number of clinicians making treatment decisions for patients with MCL that are concordant with expert consensus recommendations.

10.
Lancet Haematol ; 6(2): e100-e109, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30709431

RESUMO

BACKGROUND: Therapeutic approaches for B-cell malignancies continue to evolve, especially with regard to combination approaches. We assessed the safety and efficacy of the triplet ublituximab, umbralisib, and ibrutinib in patients with advanced B-cell malignancies. METHODS: We did an open-label, phase 1 study with dose-escalation and dose-expansion phases, at five centres in the USA. Eligible patients were aged 18 years or older with histologically confirmed lymphocytic leukaemia or relapsed or refractory B-cell non-Hodgkin lymphoma, had measurable disease, adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Patients with known CNS lymphoma, active hepatitis B or C infection, or HIV were excluded. In the dose-escalation cohort, patients were treated in cycles of 28 days with escalating doses of oral umbralisib (400, 600, or 800 mg) and fixed doses of intravenous ublituximab (900 mg) and oral ibrutinib (420 mg for patients with chronic lymphocytic leukaemia; 560 mg for patients with B-cell non-Hodgkin lymphoma) in a standard 3 × 3 design until disease progression or intolerance. In the dose-expansion phase, patients were given the recommended dose of the drug combination as determined from the dose-escalation phase. The primary endpoints were safety, dose-limiting toxicities, and the maximum tolerated dose of umbralisib, when given in combination with ublituximab and ibrutinib. Safety was assessed in patients who received at least one dose of study drug; activity was assessed in all patients who had at least one post-treatment efficacy measurement. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02006485. FINDINGS: Between Sept 2, 2014, and Nov 6, 2017, we enrolled 46 patients: 24 in the dose-escalation cohort (n=14 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=10 B-cell non-Hodgkin lymphoma) and 22 in the dose-expansion cohort (n=9 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=13 B-cell non-Hodgkin lymphoma). 46 patients received at least one dose of study drug. The maximum tolerated dose of umbralisib was not reached. The recommended dose for the dose-expansion phase was umbralisib 800 mg orally once daily plus ibrutinib orally once daily and intravenous ublituximab 900 mg administered on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, and on day 1 of cycles 9 and 12. 37 (84%) of 44 patients achieved an overall response (complete or partial response). The most common any-grade adverse events were diarrhoea (n=27 [59%]), fatigue (n=23 [50%]), infusion-related reaction (n=20 [43%]), dizziness (n=17 [37%]), nausea (n=17 [37%]), and cough (n=16 [35%]). Grade 3-4 adverse events were manageable with the most common being neutropenia (n=10 [22%]) and cellulitis (n=6 [13%]). Serious adverse events occurred in 11 (24%) of 46 patients and included rash (n=2 [4%]), pneumonia (n=2 [4%]), atrial fibrillation (n=2 [4%]), sepsis (n=2 [4%]), abdominal pain (n=1 [2%]), syncope (n=1 [2%]), cellulitis (n=1 [2%]), pneumonitis (n=1 [2%]), headache (n=1 [2%]), lung infection (n=1 [2%]), skin infection (n=1 [2%]), pleural effusion (n=1 [2%]), pericardial infusion (n=1 [2%]), upper gastrointestinal bleeding (n=1 [2%]), diarrhoea (n=1 [2%]), and weakness (n=1 [2%]). No deaths related to adverse events occurred. INTERPRETATION: The combination of ublituximab, umbralisib, and ibrutinib seems to be tolerable and is associated with encouraging activity in advanced chronic lymphocytic leukaemia and B-cell non-Hodgkin lymphoma. This triplet combination will require further investigation in future studies to improve understanding of this novel, chemotherapy-free triplet combination in the management of these cancers. FUNDING: TG Therapeutics.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Segurança , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico
11.
J Clin Oncol ; 37(6): 471-480, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30615550

RESUMO

PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Rituximab/uso terapêutico , Adulto , Fatores Etários , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , América do Norte , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Rituximab/efeitos adversos , Fatores de Tempo , Transplante Autólogo , Adulto Jovem
12.
Leuk Lymphoma ; 60(5): 1214-1223, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30424705

RESUMO

Mantle cell lymphoma (MCL) represents an aggressive B-cell lymphoma with frequent relapse and poor survival. Recently, dysregulated histone-deacetylases (HDACs) and cell cycle CDK-Rb pathway have been shown to be commonly associated with MCL pathogenesis, and are considered promising targets for relapsed-lymphoma therapy. Therefore, we investigated the single agents and combination efficacy of HDACs inhibitor Vorinostat, CDK4/6 dual-inhibitor Palbociclib on MCL cell growth/survival and underlying molecular mechanism(s) using MCL cell lines including therapy-resistant MCL cell lines. Our results showed that both inhibitors as single agents or combined, significantly suppressed the cell growth and induced apoptosis in therapy-resistant and parental MCL lines. In addition, the combination of Vorinostat and Palbociclib significantly inhibited the activation of the key molecules of the CDK4/6-Rb pathway and HDAC activity and subsequently decreased the expression of Cyclin-D1 and Bcl-2. These studies demonstrated the potential for combining these two inhibitors as a novel therapeutic approach in refractory MCL therapy.

13.
Br J Haematol ; 184(5): 744-752, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30520026

RESUMO

Relapsed or refractory non-Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad-spectrum multi-kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub-types of NHL who had received at least one prior therapy. The most common sub-types were diffuse large B-cell lymphoma (24%), follicular lymphoma, grade 1/2 (21%) and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; 21%). Most patients were heavily pre-treated, including 42% with more than four prior therapies, 67% with rituximab exposure and 24% with prior autologous transplant. In this cohort, dasatinib showed modest activity in evaluable patients with an objective response rate of 29% (7/24) and clinical benefit rate of 71% (17/24). In 32 patients with outcome data, median progression-free survival was 3 months and median overall survival was 22·4 months. There were two patients with sustained complete responses, both with PTCL-NOS histology. The side effect profile was consistent with prior studies, with pleural effusion being the most common non-haematological toxicity. Exploratory genomic analysis showed two cases of PTCL-NOS with sustained response had a common mutation in LRRK2 and high prevalence of FOXO1 mutation in relapsed/refractory follicular lymphoma.


Assuntos
Dasatinibe/administração & dosagem , Proteína Forkhead Box O1/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Linfoma não Hodgkin , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Genômica , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida
14.
Br J Haematol ; 181(6): 760-769, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29672827

RESUMO

Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1-2), and high risk (HiR, 74 patients, 24%, score 3-4), having a 3-year OS of 76% [95% confidence interval 61-88], 43% [35-51], and 11% [4-21], respectively (P < 0·001). Comparing the performance of the T cell score on OS to that of each of the previously developed models, it emerged that the new score had the best discriminant power. The new T cell score, based on clinical variables, identifies a group with very unfavourable outcomes.


Assuntos
Linfoma de Células T Periférico/mortalidade , Modelos Biológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Taxa de Sobrevida
16.
Hum Pathol ; 72: 180-190, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29170017

RESUMO

The World Health Organization classification of lymphoma recommends the subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the average number of centroblasts per high-power field in the neoplastic follicles, but does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) without enough centroblasts to meet the World Health Organization criteria for FL3. We have classified such cases as follicular large cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical features of 72 cases of this entity. The features of FLC include a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1µ, approximately twice that of small lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high Ki67 proliferation (81%). The clinical features of patients with FLC were similar to those with other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications because the diagnosis of FLC may be important for the selection of therapy.


Assuntos
Linfócitos B/patologia , Linfócitos/patologia , Linfoma Folicular/patologia , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/efeitos dos fármacos , Diagnóstico Diferencial , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Translocação Genética/genética
18.
Blood ; 131(11): 1183-1194, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29229594

RESUMO

In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n = 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiocinas/sangue , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Recidiva , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia
19.
Clin Lymphoma Myeloma Leuk ; 17(8): 488-497.e2, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28842137

RESUMO

BACKGROUND: The combination of rituximab with chemotherapy has improved the outcome of patients with follicular lymphoma (FL). However, data on Grade 3 FL (FL3) and its subtypes are lacking. The aims of the study were to determine: (1) the clinical features and outcome of patients with FL3 treated with rituximab and anthracycline-based chemotherapy; and (2) the clinical significance of the 3 subtypes of FL3. PATIENTS AND METHODS: Eighty-seven patients with Grade 1/2 FL, 84 with FL3 including 46 FL3A, 17 FL3B, and 21 follicular large cleaved cell (FL3C), and 411 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab and anthracycline-based chemotherapy, and a historical cohort of 167 patients with FL3 who received only anthracycline-based chemotherapy (FL3*) were included in this retrospective study. RESULTS: The FL3 group had a significantly better overall survival (OS) and event-free survival (EFS) compared with those with FL3* or DLBCL. No significant differences in OS were found among the 3 subtypes of FL3. However, patients with FL3B had a shorter EFS than those with FL3A and FL3C. Moreover, patients with FL3B had an outcome similar to those with DLBCL, whereas patients with FL3A and 3C had significantly better outcomes than those with DLBCL. Less than 50% of the patients with FL3B and less than 20% of the patients with FL3A and 3C have relapsed, and relapses were uncommon after 5 years. CONCLUSION: The use of rituximab with anthracycline-based chemotherapy significantly improved the survival of patients with FL3 and should be considered the benchmark by which other therapies for FL3 are evaluated in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Rituximab/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento
20.
Am J Hematol ; 92(8): 806-813, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28699667

RESUMO

DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX-11 or a low Ki-67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma. RISK STRATIFICATION: The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki-67 proliferative index if available. The median OS for the low-risk group was not reached (5-year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group. RISK-ADAPTED THERAPY: For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic Regimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression-free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression-free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti-angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK] inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/terapia , Terapia Combinada , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Célula do Manto/etiologia , Linfoma de Célula do Manto/mortalidade , Prognóstico , Recidiva , Medição de Risco , Fatores de Risco
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