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1.
Blood ; 142(7): 621-628, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37319432

RESUMEN

Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study's primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Supervivencia sin Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/etiología , Trasplante Autólogo , Linfoma de Células T Periférico/tratamiento farmacológico , Linfocitos T/patología , Trasplante de Células Madre
2.
Ann Hematol ; 103(1): 185-198, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37851072

RESUMEN

Antibodies targeting PD-1 or 4-1BB achieve objective responses in follicular lymphoma (FL), but only in a minority of patients. We hypothesized that targeting multiple immune receptors could overcome immune resistance and increase response rates in patients with relapsed/refractory FL. We therefore conducted a phase 1b trial testing time-limited therapy with different immunotherapy doublets targeting 4-1BB (utomilumab), OX-40 (ivuxolimab), and PD-L1 (avelumab) in combination with rituximab among patients with relapsed/refractory grade 1-3A FL. Patients were enrolled onto 2 of 3 planned cohorts (cohort 1 - rituximab/utomilumab/avelumab; cohort 2 - rituximab/ivuxolimab/utomilumab). 3+3 dose escalation was followed by dose expansion at the recommended phase 2 dose (RP2D). Twenty-four patients were enrolled (16 in cohort 1 and 9 in cohort 2, with one treated in both cohorts). No patients discontinued treatment due to adverse events and the RP2D was the highest dose level tested in both cohorts. In cohort 1, the objective and complete response rates were 44% and 19%, respectively (50% and 30%, respectively, at RP2D). In cohort 2, no responses were observed. The median progression-free survivals in cohorts 1 and 2 were 6.9 and 3.2 months, respectively. In cohort 1, higher density of PD-1+ tumor-infiltrating T-cells on baseline biopsies and lower density of 4-1BB+ and TIGIT+ T-cells in on-treatment biopsies were associated with response. Abundance of Akkermansia in stool samples was also associated with response. Our results support a possible role for 4-1BB agonist therapy in FL and suggest that features of the tumor microenvironment and stool microbiome may be associated with clinical outcomes (NCT03636503).


Asunto(s)
Antineoplásicos , Linfoma Folicular , Humanos , Rituximab , Linfoma Folicular/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Inmunoterapia , Microambiente Tumoral
3.
Blood ; 137(10): 1353-1364, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-32871584

RESUMEN

T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune "neighborhoods" in which malignant B cells are surrounded by exceptionally high numbers of PD-L1-expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types.


Asunto(s)
Histiocitos/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Linfocitos T/inmunología , Escape del Tumor , Antígeno B7-H1/análisis , Antígeno B7-H1/inmunología , Histiocitos/patología , Humanos , Linfoma de Células B Grandes Difuso/patología , Receptor de Muerte Celular Programada 1/análisis , Linfocitos T/patología
4.
JAMA ; 330(6): 528-536, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37552303

RESUMEN

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.


Asunto(s)
Antraciclinas , Antibióticos Antineoplásicos , Atorvastatina , Fármacos Cardiovasculares , Cardiopatías , Linfoma , Femenino , Humanos , Persona de Mediana Edad , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Atorvastatina/uso terapéutico , Método Doble Ciego , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Fármacos Cardiovasculares/uso terapéutico , Linfoma/tratamiento farmacológico , Cardiopatías/inducido químicamente , Cardiopatías/fisiopatología , Cardiopatías/prevención & control , Estudios de Seguimiento , Masculino , Adulto , Anciano
5.
Blood ; 135(22): 1929-1945, 2020 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-32187362

RESUMEN

Erdheim-Chester disease (ECD) is a rare histiocytosis that was recently recognized as a neoplastic disorder owing to the discovery of recurrent activating MAPK (RAS-RAF-MEK-ERK) pathway mutations. Typical findings of ECD include central diabetes insipidus, restrictive pericarditis, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific inflammatory and fibrotic findings on histopathologic review of tissue specimens. Additionally, the association of ECD with unusual tissue tropism and an insidious onset often results in diagnostic errors and delays. Most patients with ECD require treatment, except for a minority of patients with minimally symptomatic single-organ disease. The first ECD consensus guidelines were published in 2014 on behalf of the physicians and researchers within the Erdheim-Chester Disease Global Alliance. With the recent molecular discoveries and the approval of the first targeted therapy (vemurafenib) for BRAF-V600-mutant ECD, there is a need for updated clinical practice guidelines to optimize the diagnosis and treatment of this disease. This document presents consensus recommendations that resulted from the International Medical Symposia on ECD in 2017 and 2019. Herein, we include the guidelines for the clinical, laboratory, histologic, and radiographic evaluation of ECD patients along with treatment recommendations based on our clinical experience and review of literature in the molecular era.


Asunto(s)
Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/terapia , Ensayos Clínicos como Asunto , Enfermedad de Erdheim-Chester/genética , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/genética , Histiocitosis de Células de Langerhans/terapia , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Masculino , Terapia Molecular Dirigida , Mutación , Pronóstico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética
6.
Blood ; 134(14): 1132-1143, 2019 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-31292114

RESUMEN

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.


Asunto(s)
Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/terapia , Médula Ósea/patología , Manejo de la Enfermedad , Regulación Leucémica de la Expresión Génica , Humanos , Inmunofenotipificación , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/patología , Mutación , Estadificación de Neoplasias , Linfocitos T/patología
7.
Blood ; 134(1): 22-29, 2019 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-30952672

RESUMEN

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Anciano , Quimioterapia de Consolidación/métodos , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/cirugía , Humanos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/inmunología , Terapia Recuperativa/métodos , Trasplante Autólogo
8.
Ann Hematol ; 100(10): 2529-2539, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34304287

RESUMEN

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.


Asunto(s)
Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Linfoma Extranodal de Células NK-T/inmunología , Linfoma Extranodal de Células NK-T/terapia , Linfocitos T/inmunología , Adulto , Anciano , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/terapia , Femenino , Humanos , Inmunoterapia Adoptiva , Linfoma Extranodal de Células NK-T/complicaciones , Masculino , Persona de Mediana Edad , Linfocitos T/trasplante , Resultado del Tratamiento , Adulto Joven
9.
N Engl J Med ; 377(26): 2531-2544, 2017 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-29226797

RESUMEN

BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. RESULTS: Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. CONCLUSIONS: In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).


Asunto(s)
Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso/terapia , Receptores de Antígenos de Linfocitos T/uso terapéutico , Linfocitos T/trasplante , Adulto , Anciano , Antígenos CD19 , Biomarcadores/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Interleucinas/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/inducido químicamente , Neutropenia/inducido químicamente , Receptores de Antígenos de Linfocitos T/sangre , Tasa de Supervivencia , Linfocitos T/inmunología , Adulto Joven
10.
J Drugs Dermatol ; 19(8): 803-805, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32845598

RESUMEN

Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments. J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943.


Asunto(s)
Alquilantes/administración & dosificación , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Mecloretamina/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/patología , Humanos , Piel/efectos de los fármacos , Piel/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , Resultado del Tratamiento
11.
Mod Pathol ; 32(6): 830-843, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30626916

RESUMEN

Recent studies have demonstrated recurrent activating mutations involving the classical MAPK and PI3K signaling pathways in a large proportion of histiocytic neoplasms, such as Langerhans cell histiocytosis. However, very little is known about the molecular genetics of histiocytic sarcoma, a rare aggressive malignant neoplasm that shows pathologic characteristics of mature macrophages. Here we report the genomic characteristics of a large cohort of histiocytic sarcomas (n = 28) using a targeted next-generation sequencing approach to identify driver alterations. We identified recurrent mutations involving the RAS-MAPK signaling pathway (MAP2K1, KRAS, NRAS, BRAF, PTPN11, NF1, CBL) in a majority (57%) of histiocytic sarcoma cases and report a clinical response to a MEK inhibitor (Cobimetinib) in a patient with a NF1-mutated histiocytic sarcoma. A smaller subset of cases (21%) also showed mutations resulting in activation of the PI3K signaling pathway (PTEN, MTOR, PIK3R1, PIK3CA). In addition, the tumor-suppressor gene CDKN2A was the most frequently altered gene (46%). Further, a subset of histiocytic sarcoma cases shows striking molecular genetic similarities to B cell lymphomas, supporting a clonal relationship between B cell neoplasms and a subset of histiocytic sarcomas. These findings support a cooperative role for MAPK, PI3K, and cyclin-CDK4/6-INK4 signaling in the pathogenesis of histiocytic sarcoma and provide a rational basis for targeting these pathways.


Asunto(s)
Sarcoma Histiocítico/genética , Sistema de Señalización de MAP Quinasas/genética , Proteínas ras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Sarcoma Histiocítico/patología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Adulto Joven
12.
Radiographics ; 39(1): 95-114, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30500304

RESUMEN

Histiocytosis describes a group of diseases that have long been considered enigmatic in the history of medicine. Recently, novel genomic analyses have identified somatic oncogenic driver mutations responsible for the pathogenesis of these entities. These discoveries have led to the recharacterization of histiocytoses as neoplastic diseases and have opened a new era of precision medicine approaches for treatment. The histiocytic disorders demonstrate a variety of imaging manifestations involving multiple organ systems, and radiologists play a major role in diagnosis and monitoring. An up-to-date knowledge of the novel genomic discoveries and their implications is essential for radiologists to understand the new approaches to treating histiocytic disorders and to contribute as key members of the multidisciplinary treatment team. This article provides a cutting-edge review of the novel concepts in histiocytosis, with a focus on recent genomic discoveries and precision medicine approaches to treating the disease, and describes imaging manifestations with correlative histologic and genomic findings, with an emphasis on adult-onset cases and uncommon subtypes. ©RSNA, 2018.


Asunto(s)
Histiocitosis/diagnóstico por imagen , Medicina de Precisión , Femenino , Genómica , Histiocitosis/genética , Histiocitosis/patología , Histiocitosis/terapia , Humanos , Masculino , Mutación , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores
13.
J Cancer Educ ; 34(2): 229-233, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-29052110

RESUMEN

Despite a growing number of clinical trials and supportive care programs for cancer survivors, recruitment of patients for these opportunities during the survivorship phase of care is challenging. We piloted a novel process to systematically educate patients about available research studies and supportive care programs as part of a survivorship care visit. Between 3/2015 and 8/2015, patients seen in the Adult Survivorship Program who had not previously received a treatment summary and survivorship care plan (TS/SCP) were provided with one accompanied by a list of survivorship research studies and care programs tailored to their diagnosis. Survivorship providers discussed the opportunities and recorded whether the patient was interested in relevant studies and placed referrals to study staff. Following the visit, we tracked study enrollment and surveyed patients about their experience. Fifty of 56 (89%) pilot participants completed the survey. Almost all (98%) reported that the TS/SCP visit and document helped with knowledge of research opportunities and supportive care interventions. Following receipt of the TS/SCP, 44% were interested in at least one study and in further follow-up with research staff. Of the 30 survivors eligible for at least one study, 6 (20%) have enrolled in at least one study to date. This pilot program demonstrates that the systematic sharing of available clinical studies and supportive care programming as part of a survivorship care plan visit is feasible and well received by cancer survivors and may facilitate and enhance accrual to clinical trials in the survivorship phase of care.


Asunto(s)
Actitud Frente a la Salud , Investigación Biomédica , Supervivientes de Cáncer , Adulto , Anciano , Ensayos Clínicos como Asunto , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Neoplasias/terapia , Planificación de Atención al Paciente , Proyectos Piloto , Encuestas y Cuestionarios , Supervivencia
14.
Aesthet Surg J ; 39(Suppl_1): S3-S13, 2019 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-30715173

RESUMEN

National Comprehensive Cancer Network (NCCN) guidelines represent the consensus standard of care for diagnosis and management of the majority of known cancers. NCCN guidelines on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) have been recognized by the US Food and Drug Administration and widely advocated by national specialty societies. Consensus guidelines have helped create a treatment standardization for BIA-ALCL at all stages of disease. NCCN guidelines are evidence-based where possible and utilize expert consensus opinion to fill in gaps that may exist. NCCN undergoes annual panel review by multidisciplinary faculty members, and this article represents the most up-to-date 2019 guidelines. Recommendations focus on parameters for achieving reliable diagnosis and disease management and emphasize the critical role for complete surgical ablation. Suggestions for adjunct treatments and chemotherapy regimens are included for advanced BIA-ALCL with lymph node involvement. BIA-ALCL recurrence and management of unresectable disease, and organ metastasis are addressed. Adherence to recognized BIA-ALCL guidelines ensures patients receive the most current efficacious treatment available.


Asunto(s)
Implantes de Mama/efectos adversos , Linfoma Anaplásico de Células Grandes/etiología , Femenino , Humanos , Metástasis Linfática , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/terapia , Recurrencia Local de Neoplasia
15.
Oncologist ; 23(5): 624-630, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29284757

RESUMEN

BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma. However, elderly patients are often not considered ASCT candidates based on age alone. SUBJECTS, MATERIALS, AND METHODS: A retrospective analysis of patients ≥70 years of age with a diagnosis of Hodgkin or non-Hodgkin lymphoma receiving ASCT between 2000 and 2016 at two partner institutions was performed. Clinical data were extracted from institutional databases and individual medical records. Multivariate analysis was performed to examine the association of clinical variables with transplant outcomes. RESULTS: One hundred seven patients were identified. Median age at transplant was 72 years (range, 70-79). The most common lymphoma subtype was diffuse large B-cell (n = 63, 59%). Median time to neutrophil and platelet engraftment were 10 and 12 days, respectively. With a median follow-up for survivors of 20 months following ASCT (range, 6 months to 13.1 years), estimates for 2-year progression-free survival and overall survival were 58% (95% confidence interval [CI], 48%-67%) and 65% (95% CI, 55%-74%), respectively. Two-year estimate for relapse was 34% (95% CI, 25%-44%) and nonrelapse mortality (NRM) was 7% (95% CI, 3%-14%). Multivariate analysis showed that more recent date of transplant was associated with lower NRM. The Hematopoietic Cell Transplantation-Comorbidity Index score was not predictive of NRM in this data set (high-risk vs. low-risk, hazard ratio 3.45, p = .065). CONCLUSION: Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. IMPLICATIONS FOR PRACTICE: Although high-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma, elderly patients are often not considered candidates due to concern for excess toxicity and mortality. This retrospective study showed favorable transplant outcomes, including survival and toxicity, in a large cohort of lymphoma patients over 70 years of age who underwent ASCT. Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos
16.
Blood ; 125(9): 1394-402, 2015 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-25573987

RESUMEN

Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Inmunoconjugados/uso terapéutico , Antígeno Ki-1/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brentuximab Vedotina , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Adulto Joven
18.
Br J Haematol ; 173(1): 89-95, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26729345

RESUMEN

Chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma (MCL). The achievement of complete remission (CR) and minimal residual disease (MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine (RB/RC). This phase 2 study (NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD-evaluable patients who completed treatment, 93% achieved MRD negativity after RB/RC. In conclusion, RB/RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/mortalidad , Adolescente , Adulto , Anciano , Clorhidrato de Bendamustina/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células del Manto/sangre , Masculino , Persona de Mediana Edad , Inducción de Remisión , Rituximab/administración & dosificación , Tasa de Supervivencia
19.
Blood ; 123(20): 3095-100, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24652992

RESUMEN

This phase 2, open-label, multicenter study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, in relapsed/refractory CD30(+) non-Hodgkin lymphomas. The primary end point was objective response rate (ORR). Key secondary end points included safety, correlation of CD30 expression with response, response duration, and progression-free survival (PFS). Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks until progression or unacceptable toxicity. This planned subset analysis included patients with peripheral T-cell lymphomas (PTCLs; n = 35), specifically angioimmunoblastic T-cell lymphoma (AITL; n = 13) and PTCL not otherwise specified (n = 22). Median age was 64 years; 63% were refractory to most recent therapy. Of 34 evaluable patients, ORR was 41% (8 complete remissions [CRs], 6 partial remissions [PRs]), and ORR was 54% in AITL (5 CRs, 2 PRs) with median PFS of 6.7 months thus far. No correlation between CD30 expression per central review and response was observed. Safety data were consistent with the known profile of brentuximab vedotin, and included at least grade 3 events of neutropenia (14%), peripheral sensory neuropathy, and hyperkalemia (9% each). In summary, brentuximab vedotin showed antitumor activity in patients with relapsed PTCL particularly AITL. This trial was registered at www.clinicaltrials.gov as #NCT01421667.


Asunto(s)
Inmunoconjugados/uso terapéutico , Linfoma de Células T/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Brentuximab Vedotina , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/farmacocinética , Antígeno Ki-1/análisis , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología
20.
Am J Hematol ; 96(4): E95-E98, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33373063
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