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1.
Blood Adv ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35008100

RESUMO

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal LDH, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (HR 0.278, 95% CI: 0.153-0.506; p=<0.0001) and ≤ 2 prior lines of therapy (HR 0.485, 95% CI: 0.274-0.859; p=0.0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR 0.352, 95% CI: 0.186-0.663; p=0.0013) and ≤ 2 prior lines of therapy (HR 0.476, 95% CI: 0.257-0.882; p=0.0183) were associated with improved survival. In the largest single center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those received less than two lines of therapy have particularly excellent outcomes.

2.
Blood Adv ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015825

RESUMO

About 70% of patients with large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) who achieve a partial response (PR) or a stable disease (SD) on day 30 (D30) PET-CT scan progress, but predictive factors of progression are unknown. This a retrospective study of patients with LBCL treated with axi-cel at MD Anderson Cancer Center between 01/2018 and 02/2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to complete response (CR). Among 95 patients with D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day -5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (p=0.05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was lower D30 SUVmax (p<0.001), and all patients with and D30 SUVmax ≥10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed when comparing patients who converted from D30 PR/SD to subsequent CR to those who had been in CR since D30 (p=0.19). Novel predictive and prognostic markers based on tissue biopsy and non-invasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

3.
Haematologica ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34758610

RESUMO

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their FDA approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day Major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, 4 exacerbations of heart failure/cardiomyopathy, 4 cerebrovascular accidents, 3 myocardial infarctions (MI), and one patient died due to MI. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival (PFS) or with overall survival (OS). Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited followup, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

4.
Blood Adv ; 5(14): 2799-2806, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264268

RESUMO

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , Humanos
5.
Nat Commun ; 12(1): 2877, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001881

RESUMO

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica/métodos , Heterogeneidade Genética , Linfoma de Célula do Manto/genética , Análise de Célula Única/métodos , Microambiente Tumoral/genética , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Humanos , Imidazóis/farmacologia , Linfoma de Célula do Manto/diagnóstico por imagem , Linfoma de Célula do Manto/tratamento farmacológico , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Naftoquinonas/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Análise de Sequência de RNA/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
6.
Blood ; 137(23): 3272-3276, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33534891

RESUMO

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities.

7.
Br J Haematol ; 192(3): 560-567, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33517581

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed.


Assuntos
Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colúmbia Britânica/epidemiologia , Criança , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Progressão , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
8.
Leuk Lymphoma ; 62(6): 1361-1369, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33480830

RESUMO

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.


Assuntos
Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-myc , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia/genética , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética
11.
J Pediatr Hematol Oncol ; 43(4): e535-e538, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32366782

RESUMO

Neurofibromatosis Type 1 (NF1) is a genetic disorder with an incidence of 1 in 2600 to 3000 individuals. It is a clinical diagnosis characterized by café-au-lait macules, neurofibromas, and axillary and/or groin freckling. Because of genetic mutations in the NF1 gene affecting the Ras/mitogen-activated protein kinase pathway, there is also risk of associated soft tissue sarcomas and hematologic malignancies. However, reports of classic Hodgkin lymphoma in patients with NF1 are sparse. We report an adolescent with NF1 who developed classic Hodgkin lymphoma. Although there is an unclear association between mutations in the NF1 gene and classic Hodgkin lymphoma, further studies are warranted.


Assuntos
Doença de Hodgkin/complicações , Neurofibromatose 1/complicações , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Manchas Café com Leite/complicações , Manchas Café com Leite/tratamento farmacológico , Manchas Café com Leite/genética , Manchas Café com Leite/patologia , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Humanos , Mutação , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Neurofibromina 1/genética
12.
Int J Radiat Oncol Biol Phys ; 109(5): 1414-1420, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309978

RESUMO

PURPOSE: We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS AND MATERIALS: Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement. RESULTS: From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity. CONCLUSIONS: This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. CLINICALTRIALS.GOV: NCT04465162.


Assuntos
Linfoma de Zona Marginal Tipo Células B/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Estimativa de Kaplan-Meier , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/radioterapia , Intervalo Livre de Progressão , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Recidiva , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Fatores de Tempo , Resultado do Tratamento
13.
EJHaem ; 1(1): 272-276, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32864660

RESUMO

Classical Hodgkin lymphoma (HL) patients achieve excellent outcomes; therefore, treatment de-escalation strategies to spare toxicity have been prioritized. In a large randomized trial of early stage HL patients, omission of chemotherapeutic agents including bleomycin from the standard ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen was not found to be non-inferior; however the effect of partial omission is unknown. We investigated the effect of bleomycin omission on outcome for 150 early stage HL patients. At eight years, freedom from relapse was 99% for both patients who received complete or incomplete bleomycin, which is reassuring for patients requiring bleomycin omission due to toxicity.

14.
Blood Adv ; 4(16): 3943-3951, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32822484

RESUMO

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.


Assuntos
Síndromes Neurotóxicas , Síndrome da Leucoencefalopatia Posterior , Antígenos CD19/uso terapêutico , Produtos Biológicos , Humanos , Imunoterapia Adotiva , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia
16.
Blood Adv ; 4(13): 2871-2883, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32589728

RESUMO

The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.


Assuntos
Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Antígenos CD19/uso terapêutico , Produtos Biológicos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Taxa de Sobrevida
17.
Leuk Lymphoma ; 61(6): 1380-1387, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31971032

RESUMO

In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of follicular lymphoma (FL), the results were incongruent. We conducted a retrospective matched-pair analysis to compare the outcome of patients with advanced stage FL, receiving frontline BR (N = 73) or R-CHOP (N = 73), matched by age, gender, stage, and FL International Prognostic Index score. On multivariable analysis, baseline maximum standardized uptake value (SUVmax) >13 was associated with use of R-CHOP (p = .001). After a median follow-up of 69 months for the BR arm and 126 months for the R-CHOP arm, 5-year PFS was 80% and 70%, respectively (p = .07). After adjusting for SUVmax >13, the trend for better PFS in BR was not maintained. Prospective studies are needed to validate the role of pretreatment SUVmax as a stratification factor in future randomized therapeutic trials in FL.


Assuntos
Linfoma Folicular , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Folicular/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Rituximab/uso terapêutico , Vincristina/efeitos adversos
18.
Cancer Med ; 9(2): 663-670, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31808316

RESUMO

Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty-six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26-78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2-year progression-free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2-year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation.


Assuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Dura-Máter/patologia , Linfoma de Zona Marginal Tipo Células B/mortalidade , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
19.
Blood Adv ; 3(9): 1356-1367, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31036721

RESUMO

Radiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.


Assuntos
Doença de Hodgkin/terapia , Linfócitos/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Linfócitos/citologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Acta Haematol ; 139(1): 67-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29402766

RESUMO

BACKGROUND: Acute pancreatitis is an uncommon complication of anti-myeloma agents. Ixazomib is a first-in-class oral proteasome inhibitor to receive regulatory approval for the treatment of multiple myeloma. This case report describes the first case of ixazomib-associated pancreatitis. CASE PRESENTATION: An 80-year-old female with relapsed multiple myeloma presented with severe diarrhea, nausea, vomiting, abdominal pain, and acute renal failure 3 weeks after starting ixazomib and dexamethasone for disease progression. An extensive workup revealed acute pancreatitis without a definitive cause. Her condition improved with supportive measures and the discontinutation of ixazomib. The latter was suspected as the probable etiology of the patient's acute pancreatitis, given no clear alternative causes and the temporal relationship between initiating ixazomib and the development of her symptoms. CONCLUSIONS: Practitioners should include acute pancreatitis as part of their differential diagnosis in patients on ixazomib treatment who present with gastrointestinal symptoms.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Boro/efeitos adversos , Glicina/análogos & derivados , Mieloma Múltiplo/complicações , Pancreatite/diagnóstico , Pancreatite/etiologia , Doença Aguda , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos de Boro/uso terapêutico , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico
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