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1.
Br J Haematol ; 168(5): 654-62, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25312994

RESUMEN

The most effective strategy to prevent central nervous system (CNS) dissemination in diffuse large B-cell lymphoma (DLBCL) remains an important, unmet clinical need. Herein, we report a retrospective analysis of risk-tailored CNS prophylaxis in 200 human immunodeficiency virus-negative adults with DLBCL treated with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or similar. High risk of CNS relapse was defined by involvement of specific extranodal organs, or simultaneous presence of advanced stage and high serum lactate dehydrogenase level; CNS prophylaxis with high-dose methotrexate ± intrathecal chemotherapy (IT) was routinely used in high-risk patients diagnosed after 2007. CNS relapse risk was low in 93 patients and high in 107; 40 high-risk patients received prophylaxis, which consisted of IT alone in 7. At a median follow-up of 60 months, one low-risk and nine high-risk patients (1% vs. 8%; P = 0·01) experienced CNS relapse. In the high-risk group, CNS relapses occurred in 8/67 (12%) patients who did not receive prophylaxis and in 1/40 (2·5%) patients who did; the latter occurred in a patient managed with IT alone. CNS relapse rate was 12% (9/74) for patients treated with "inadequate" prophylaxis (none or IT only) and 0% (0/33) for patients managed with intravenous prophylaxis (P = 0·03). In conclusion, high-dose methotrexate-based prophylaxis significantly reduces CNS failures in high-risk patients stratified by involvement of specific extranodal sites and International Prognostic Index.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/secundario , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Vincristina/administración & dosificación
2.
Biol Blood Marrow Transplant ; 20(9): 1444-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24907625

RESUMEN

The management of Hodgkin's lymphoma (HL) recurring after allogeneic stem cell transplantation is challenging. We retrospectively describe 18 adults treated with bendamustine followed by escalated donor lymphocyte infusion. Hematological toxicity was manageable (39% grade III to IV neutropenia and 28% grade III to IV thrombocytopenia). The overall response rate was 55%, with 3 complete and 7 partial responses. Median overall and progression-free survival were 11 (range, 1 to 52) and 6 (range, 1 to 28) months, respectively. One-year overall survival of responders (complete or partial) was 70% (95% confidence interval, 42% to 98%), although it was only 16% for nonresponders (n = 8). Our data show that bendamustine followed by donor lymphocyte infusion is feasible and can be efficacious as salvage treatment in HL relapsing after an allograft.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Compuestos de Mostaza Nitrogenada/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Antineoplásicos Alquilantes/administración & dosificación , Clorhidrato de Bendamustina , Humanos , Linfocitos , Recurrencia Local de Neoplasia , Compuestos de Mostaza Nitrogenada/administración & dosificación
3.
Br J Haematol ; 164(6): 834-40, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24383942

RESUMEN

'Multifocal bone lymphoma' or 'polyostotic lymphoma' is a neoplasm with exclusive multifocal involvement of the skeleton, without affecting lymph nodes or other soft tissues. Knowledge on this uncommon condition is limited because the related literature is sparse and fragmentary. We reviewed cases of multifocal bone diffuse large B-cell lymphoma (MB-DLBCL) registered in a clinico-pathological database of the International Extranodal Lymphoma Study Group that includes 499 cases of bone lymphoma. Clinical features, management and prognosis of 37 MB-DLBCL patients and 63 'controls' (stage-IV DLBCL and skeletal involvement) were analysed. Presentation and treatment of MB-DLBCL and controls were identical. At a median follow-up of 52 months (10-189), MB-DLBCL patients exhibited a significantly better response rate (92% vs. 65%; P = 0·002), progression-free survival (5-year: 56 ± 9% vs. 34 ± 6%; P = 0·003) and overall survival (5-year: 74 ± 8% vs. 36 ± 7%; P = 0·002). Among MB-DLBCL patients, the use of post-chemo radiotherapy was associated with better overall survival (5-year: 83 ± 12% vs. 55 ± 16%; P = 0·003). Two MB-DLBCL patients (5·4%) with spine and skull involvement experienced central nervous system (CNS) relapse. Thus, MB-DLBCL patients exhibit a significantly better prognosis compared to patients with advanced-stage DLBCL, and should be treated with conventional anthracycline-based chemotherapy, keeping intensified treatment for relapsing cases, considering involved-field radiotherapy, and CNS prophylaxis in high-risk patients.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto , Anciano , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/radioterapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
4.
Oncologist ; 19(3): 291-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24567283

RESUMEN

INTRODUCTION: The clinical features, management, and prognosis of stage I-II diffuse large B-cell lymphoma of the bone (PB-DLBCL) included in an international database of 499 lymphoma patients with skeletal involvement were reviewed. METHODS: HIV-negative patients (n = 161) with diffuse large B-cell lymphoma of the bone (PB-DLBCL) after complete staging workup were considered. The primary objective of this study was to identify the most effective treatment modality; the secondary objectives were to define the contribution of irradiation fields and doses and the pattern of relapse. RESULTS: Median age was 55 years (range, 18-99 years), with a male/female ratio of 1:2; 141 (87%) patients had stage I, 14 (9%) had B symptoms, 37 (23%) had bulky lesion, 54 (33%) showed elevated lactate dehydrogenase serum levels, and 25 (15%) had fracture. Thirteen (8%) patients received chemotherapy alone, 23 (14%) received radiotherapy alone, and 125 (78%) received both treatments. The response to the first-line treatment was complete in 131 of 152 assessed patients (complete response rate, 86%; 95% confidence interval [CI], 81%-91%) and partial in 7, with an overall response rate of 91% (95% CI, 87%-95%). At a median follow-up of 54 months (range, 3-218), 107 (67%) patients remained relapse-free, with a 5-year progression-free survival of 68% (SE: 4). Four (2.5%) patients had meningeal relapse; 119 patients were alive (113 disease-free), with a 5-year overall survival of 75% (SE: 4). Patients managed with primary chemotherapy, whether followed by radiotherapy or not, had a significantly better outcome than patients treated with primary radiotherapy, whether followed by chemotherapy or not. The addition of consolidative radiotherapy after primary chemotherapy was not associated with improved outcome; doses >36 Gy and the irradiation of the whole affected bone were not associated with better outcome. CONCLUSION: Patients with PB-DLBCL exhibit a favorable prognosis when treated with primary anthracycline-based chemotherapy whether followed by radiotherapy or not. In patients treated with chemoradiotherapy, the use of larger radiation fields and doses is not associated with better outcome. Central nervous system dissemination is a rare event in PB-DLBCL patients.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Quimioradioterapia , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento , Adulto Joven
6.
J Clin Oncol ; 33(33): 3903-10, 2015 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-26282634

RESUMEN

PURPOSE: Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma. PATIENTS AND METHODS: HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients. RESULTS: Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 10(6)/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. CONCLUSION: The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.


Asunto(s)
Antimetabolitos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/terapia , Linfoma de Células B/terapia , Trasplante de Células Madre/métodos , Adolescente , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Terapia Combinada , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Estudios de Seguimiento , Humanos , Inmunoterapia/métodos , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Dosis Máxima Tolerada , Persona de Mediana Edad , Medición de Riesgo , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
7.
Leuk Lymphoma ; 55(8): 1796-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24295130

RESUMEN

Indolent lymphomas primarily involving the skeleton (iPBL) represent < 1% of all primary bone lymphomas. The management and prognosis have not been previously described. Patients with primary and secondary iPBL were selected from an international database of 499 patients with a histopathological diagnosis of non-Hodgkin lymphoma and skeleton involvement, and clinical features, management and prognosis were analyzed. Twenty-six (5%) patients had an iPBL. Ten patients had small lymphocytic lymphoma, 10 had follicular lymphoma and six had lymphoplasmacytic lymphoma. Eleven patients had limited stage and 15 had advanced disease. The overall response rate was 73% (95% confidence interval [CI] = 57-89%). Median follow-up was 58 months, and the 5- and 10-year progression-free survival (PFS) rates were 37 ± 10% and 25 ± 12%, respectively. Nine patients are alive, with 5- and 10-year overall survival (OS) rates of 46 ± 10% and 29 ± 11%, respectively. Patients with small lymphocytic lymphoma showed significantly better outcome than patients with follicular lymphoma. Performance status and stage of disease were independently associated with OS. The prognosis of patients with primary bone lymphoplasmacytic or follicular lymphoma was less favorable.


Asunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias Óseas/terapia , Manejo de la Enfermedad , Linfoma/diagnóstico , Linfoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Femenino , Humanos , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento
8.
Transpl Int ; 17(10): 603-8, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15517167

RESUMEN

Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney-pancreas transplanted (KP) patients without kidney rejection. Two fine-needle aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were obtained 14 days after transplantation. Immunosuppression was based on anti-Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate as maintenance therapy. Ten matched healthy subjects were chosen as controls for PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte expression of pro/anti-apoptotic molecules were analysed by flow cytometry analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL were higher in transplanted patients than in controls. Apoptotic rate and lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic molecules were evident after ATG induction.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Apoptosis , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Riñón/fisiopatología , Ácido Micofenólico/análogos & derivados , Trasplante de Páncreas , Adulto , Biomarcadores/metabolismo , Ciclosporina/uso terapéutico , Regulación hacia Abajo , Proteína Ligando Fas , Humanos , Activación de Linfocitos , Linfocitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Ácido Micofenólico/uso terapéutico , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
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