Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Mod Pathol ; 37(7): 100516, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763418

RESUMEN

Follicular lymphoma (FL) is the most frequent indolent lymphoma. Some patients (10%-15%) experience histologic transformation (HT) to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis.We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104; 62 from nontransformed and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve. The clinicogenetic nomogram included the mutational status of 3 genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk Follicular Lymphoma International Prognostic Index and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs 0.51 in the high-risk group and, at 60 months, 0.71 vs 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs 0.54 in the high-risk group at 24 months, and 0.71 vs 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (Follicular Lymphoma International Prognostic Index) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.


Asunto(s)
Linfoma Folicular , Linfoma de Células B Grandes Difuso , Nomogramas , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Medición de Riesgo , Anciano de 80 o más Años , Mutación , Factores de Riesgo , Pronóstico , Biomarcadores de Tumor/genética
2.
Community Ment Health J ; 60(5): 1025-1030, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38424398

RESUMEN

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Humanos , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Trastornos Mentales/terapia , Hospitalización/estadística & datos numéricos , Enfermedad Aguda
3.
Actas Dermosifiliogr ; 115(2): 119-129, 2024 Feb.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37689349

RESUMEN

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.


Asunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Calidad de Vida , España/epidemiología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/epidemiología , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patología , Micosis Fungoide/terapia , Micosis Fungoide/patología , Síndrome de Sézary/terapia , Síndrome de Sézary/patología
4.
Actas Dermosifiliogr ; 115(2): T119-T129, 2024 Feb.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38048944

RESUMEN

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.


Asunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Calidad de Vida , España/epidemiología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patología , Micosis Fungoide/terapia , Micosis Fungoide/patología , Síndrome de Sézary/terapia , Síndrome de Sézary/patología
5.
J Eur Acad Dermatol Venereol ; 37(1): 57-64, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36017748

RESUMEN

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.


Asunto(s)
Inmunoconjugados , Linfoma Cutáneo de Células T , Trastornos Linfoproliferativos , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Femenino , Humanos , Persona de Mediana Edad , Brentuximab Vedotina/uso terapéutico , Inmunoconjugados/efectos adversos , Neoplasias Cutáneas/patología , Micosis Fungoide/patología , Síndrome de Sézary/patología , Sistema de Registros , Antígeno Ki-1
6.
Hematol Oncol ; 33(4): 151-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25407794

RESUMEN

The use of PET in patients with marginal zone B cell lymphoma (MZL) is controversial because of variability of fluorodeoxyglucose (FDG) avidity. We analyzed 40 PET/CT in 25 consecutive patients to compare its performance with CT at staging and as a first-line response assessment. Sensitivity of PET/CT and CT was 96 and 76%. Mean standard uptake value was 6.1, 6.9 and 3.4 (p = 0.3) in nodal, extranodal and splenic subtypes, respectively. Of 17 patients (extranodal: n = 9; nodal: n = 6; splenic subtype: n = 2) with both imaging tests available at diagnosis, 8 (47%) had more involved areas with PET/CT than with CT, 75% of which were extranodal lesions. PET/CT resulted in upstaging of five patients although treatment of only two of them was changed. Responses of 15 patients with post-treatment PET/CT were the following: 9 negative and 6 positive of which 3 were isolated residual lesions. Progression was documented in two of these three patients. Response was also assessed by CT in 11 patients. Discrepancies were found in three: Two were in complete remission by CT while PET/CT detected localized residual disease; another patient was in partial remission by CT, whereas PET/CT showed only one positive lesion. Two of these three patients relapsed. Patients with negative post-treatment PET/CT did not relapse. With a median follow-up of 50 months (10-152 months), 3-year overall survival was 100 and 80% for patients with negative and positive post-treatment PET/CT (p = 0.2). Three-year disease-free survival was 86%; the negative predictive value (NPV) was 100%, and the positive predictive value (PPV) was 83.3%. Although a larger number of patients will be required to further confirm these data, we can conclude that PET/CT is a useful imaging tool for both staging and response assessment in patients with nodal and extranodal MZL as a result of its high sensitivity, NPV and PPV.


Asunto(s)
Fluorodesoxiglucosa F18/uso terapéutico , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Eur J Haematol ; 94(1): 23-30, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24520874

RESUMEN

UNLABELLED: Burkitt lymphoma (BL) is highly FDG-avid even though its usefulness in the management of these patients is still controversial. AIM: We analyzed the role of positron emission tomography/computerized tomography (PET/CT) in staging newly diagnosed patients with BL and evaluating disease after first-line chemotherapy. METHODS: Fifty-two PET/CTs were performed in 32 patients (20 at diagnosis, 27 after treatment, five to monitor residual disease). Involved areas were retrospectively compared with those observed in contrast-enhanced CT. RESULTS: Discrepancies were found in 64.7% of patients for whom results of both tests at diagnosis were available (n = 17), most of them involving extranodal sites. Regarding response assessment, discrepancies were observed in 38% of patients with both tests (5/13): residual masses detected by CT with negative PET/CT. Of 27 patients with post-treatment PET/CT, 22 were in complete remission whereas one true-positive and four false-positive lesions (two nodal and two extranodal) were detected. With a median follow-up of 27 months, 22 patients with negative PET/CT did not relapse. Thus, negative predictive value (NPV) was 100%. With respect to positive predictive value (PPV), one of five patients with positive assays after treatment died due to progression while the remaining four had false-positive lesions. Nevertheless, for these four patients, mean SUVmax at nodal sites was 4.1 vs. 14.9 at diagnosis, while mean SUVmax at extranodal sites was 3.8 vs. 12.1. Thus, with a cutoff value for SUVmax < 66% of that observed at diagnosis, PPV was also 100%. CONCLUSION: More accurate staging can be achieved using PET/CT. NPV reaches 100%, and using a ΔSUV < 66%, a high PPV is also observed.


Asunto(s)
Linfoma de Burkitt/diagnóstico , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/mortalidad , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
8.
Eur J Haematol ; 93(6): 469-75, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24853381

RESUMEN

UNLABELLED: Fludarabine-based regimens are highly effective as first-line therapy in patients with follicular lymphoma. Nevertheless, noticeable haematological toxicity has been reported using fludarabine-based regimens. AIM: To analyse the combination of low-dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as induction therapy, followed by rituximab as maintenance therapy. METHODS: We retrospectively analysed 73 patients diagnosed with low-grade follicular lymphoma treated with two different schemes: attenuated oral (AO) and standard intravenous (SIV) FCR. RESULTS: Overall response rate (ORR) was 95% (complete response rate, CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P = 0.058). 44.4% of patients underwent maintenance therapy. Grade 3-4 toxicities included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients; infectious complications: six patients. There were no treatment-related deaths. 6.8% had a secondary malignancy. Progression-free survival (PFS) was 84.6% at 12 yr. The following variables influenced PFS in multivariate analysis: Hb < 12 g/dL [HR 4.7 (95% CI 1.18-18.6)], response after induction [HR 4.9 (95% CI 1.01-24)] for PR vs. CR and [HR 21.27 (95% CI 4.33-104)] for SD/DP vs. CR. OS was 83.1% at 12 yr. The following variables significantly influenced OS in multivariate analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4-82.5), increased levels of ß2-microglobulin [HR 5.2 (95% CI 1.16-23.7)]. CONCLUSIONS: FCR allowed us to obtain a high response rate, which translated into promising progression free and overall survival with an acceptable and manageable toxicity profile, especially with the attenuated oral scheme.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidad , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Rituximab , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados
9.
Transpl Int ; 27(12): 1253-62, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25070273

RESUMEN

The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/µl vs. 0.3/µl; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.


Asunto(s)
Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Trasplante de Células Madre Hematopoyéticas , Memoria Inmunológica , Complicaciones Posoperatorias/inmunología , Subgrupos de Linfocitos T/inmunología , Viremia/inmunología , Adolescente , Adulto , Aloinjertos , Antivirales/uso terapéutico , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/mortalidad , Femenino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Especificidad del Receptor de Antígeno de Linfocitos T , Factores de Tiempo , Carga Viral , Viremia/etiología , Activación Viral , Replicación Viral , Adulto Joven
10.
Bone Marrow Transplant ; 59(3): 359-365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38167647

RESUMEN

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B , Linfoma no Hodgkin , Humanos , Persona de Mediana Edad , Supervivencia sin Enfermedad , Estudios Prospectivos , Recurrencia Local de Neoplasia , Linfoma de Células B/tratamiento farmacológico , Linfoma no Hodgkin/terapia , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento Pretrasplante/efectos adversos
11.
Clin Cancer Res ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900037

RESUMEN

PURPOSE: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

12.
Front Immunol ; 15: 1293931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38469299

RESUMEN

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.


Asunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Biomarcadores , Linfocitos T CD8-positivos/patología , Células Asesinas Naturales/patología , Lenalidomida/uso terapéutico , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/patología , Respuesta Patológica Completa
14.
Clin Cancer Res ; 28(17): 3658-3668, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35727601

RESUMEN

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.


Asunto(s)
Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Humanos , Lenalidomida/efectos adversos , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Rituximab/uso terapéutico , Resultado del Tratamiento
16.
J Immunother Cancer ; 9(6)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34158317

RESUMEN

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/inmunología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Células Supresoras de Origen Mieloide/metabolismo , Linfocitos T Reguladores/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Estudios de Casos y Controles , Ensayos Clínicos como Asunto , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/inmunología , Masculino , Persona de Mediana Edad , Células Supresoras de Origen Mieloide/efectos de los fármacos , Receptor de Muerte Celular Programada 1/metabolismo , Análisis de Supervivencia , Linfocitos T Reguladores/efectos de los fármacos , Resultado del Tratamiento
18.
Transplant Proc ; 40(9): 3102-3, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19010207

RESUMEN

Cytomegalovirus (CMV) infection causes high morbidity and mortality among allogeneic stem cell transplant recipients. Preemptive therapy with oral valganciclovir or intravenous ganciclovir has replaced universal prophylaxis. We prospectively studied 19 consecutive adult recipients of allogeneic peripheral blood stem cell transplants from May 2005 through February 2007 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. The antigenemia test was persistently negative in 8 patients (42%) and positive at least once in 11 (58%). Eight patients were treated with oral valganciclovir on an outpatient basis and they all became CMV negative after the first week of treatment. The other 3 patients received intravenous ganciclovir and were also CMV negative after the first week of treatment. No patient abandoned treatment, no severe secondary toxicity was noted, and there was no CMV-associated mortality.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/análogos & derivados , Ganciclovir/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/virología , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Administración Oral , Adolescente , Adulto , Antivirales/administración & dosificación , Ganciclovir/administración & dosificación , Enfermedad de Hodgkin/cirugía , Humanos , Inyecciones Intravenosas , Leucemia/cirugía , Persona de Mediana Edad , Síndromes Mielodisplásicos/cirugía , Estudios Prospectivos , Valganciclovir , Adulto Joven
19.
Rev Esp Med Nucl Imagen Mol ; 36(5): 298-303, 2017.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28438519

RESUMEN

OBJECTIVE: To study the usefulness of 18F-FDG PET/CT in the initial evaluation and in the response assessment in primary brain lymphoma. MATERIAL AND METHODS: A retrospective analysis was carried out on 18 patients diagnosed with primary brain lymphoma, a histological subtype of diffuse large B-cell lymphoma, on whom an initial 18F-FDG PET/CT and MRI was performed, with 7 of the cases being analysed after the completion of treatment in order to assess response and clinical follow up. RESULTS: Initial 18F-FDG PET/CT showed 26 hypermetabolic foci, whereas 46 lesions were detected by MRI. The average SUV maximum of the lesions was 17.56 with T/N 3.55. The concordance of both tests for identifying the same number of lesions was moderate, obtaining a kappa index of 0.395 (P<.001). In the evaluation of treatment, MRI identified 16 lesions compared to 7 pathological accumulations observed by 18F-FDG PET/CT. The concordance of both tests to assess type of response to treatment was moderate (kappa index 0.41) (P=.04). In both the initial evaluation and the assessment of the response to treatment, PET/CT led to a change strategy in 22% of patients who had lesions outside the cerebral parenchyma. CONCLUSIONS: MRI appears to be the method of choice for detecting brain disease in patients with primary brain lymphoma, whereas 18F-FDG PET/CT seems to play a relevant role in the assessment of extra-cerebral disease.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Neuroimagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Anciano , Neoplasias Encefálicas/terapia , Femenino , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA