RESUMEN
BACKGROUND: The purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades. METHODS: Our single centre experience in the treatment of 98 de novo PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy; 30 were irradiated after chemotherapy, although not receiving rituximab and 20 received rituximab without radiotherapy consolidation. Eleven patients received chemotherapy only. RESULTS: Sixty-one (62.2%) patients achieved a complete response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial responders, 21 obtained a complete response after radiotherapy. At the end of their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial response (6.1%). Eleven patients relapsed within the first 2 years of follow-up. The 17-year overall survival is 72.0% (15 patients died); progression-free and disease-free survival are 67.6% and 88.4%, respectively. A statistically significant difference in overall and progression-free survival was noted among treatment groups, although no disease-free survival difference was documented. CONCLUSIONS: Our data indicate that a third-generation regimen like MACOP-B could be considered a suitable first-line treatment. Mediastinal consolidation radiotherapy impacts on survival and complete response rates and remains a good strategy to convert partial into complete responses. Data suggest that radiotherapy may be avoided in patients obtaining a complete response after (immuno)chemotherapy, but this requires confirmation with further ad hoc studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/terapia , Neoplasias del Mediastino/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Inmunoterapia , Leucovorina/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/radioterapia , Masculino , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/radioterapia , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is an orphan disease. Chemotherapy is usually reserved to patients presenting with single system multifocal (SS-m) or multisystem (MS) disease but due to the lack of randomized studies no standard first line therapy has been defined yet. Pediatric regimens based on the vinblastine/prednisone backbone are not well tolerated in adults and probably less effective. We previously demonstrated high efficacy of the dose dense polichemotherapy regimen MACOP-B in 7 adult patients with SS-m or MS-LCH, in terms of high response rate and durable responses. Here we report an update of these data with the purpose of evaluating the long term efficacy of MACOP-B in adult LCH. METHODS: Clinical data of all adult LCH patients (n = 17) diagnosed and treated at our Institution during the past 20-year period were retrospectively reviewed. RESULTS: A total of 11 patients (6 with SS-m and 5 with MS-LCH) were treated with MACOP-B from 1995 to 2014. The overall response rate was confirmed to be 100 %, with a complete response of 73 % and a partial response rate of 27 %. Overall progression free survival was 64 %, and disease free survival after achievement of initial CR was 87 %. Overall survival rate was 82 % after 6.7 years of median follow-up. CONCLUSIONS: These data confirm high activity of MACOP-B in adult LCH, indicating that a substantial fraction of patients achieve long lasting responses and can be cured with this therapeutic approach.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis de Células de Langerhans/epidemiología , Adolescente , Adulto , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Histiocitosis de Células de Langerhans/patología , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Prednisolona/administración & dosificación , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m(2) biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Borónicos/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazinas/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Trasplante de Médula Ósea , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/efectos adversos , Bortezomib , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , Humanos , Linfoma no Hodgkin/radioterapia , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Uso Fuera de lo Indicado , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Transducción de Señal/efectos de los fármacos , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Bronchial-associated lymphoid tissue (BALT) lymphoma is an extranodal primary pulmonary lymphoma. The optimal therapy for this rare disease is still debated, and few heterogeneous data are available in literature. The aim of our study was to critically review data of patients with BALT lymphoma treated in first-line therapy with fludarabine and mitoxantrone-containing regimens (with or without rituximab) to investigate the effectiveness and the safety of this approach and patients' survival. An observational retrospective study was performed on homogenous clinical data from 17 patients with biopsy-proven diagnosis of BALT. All the patients were treated with fludarabine and mitoxantrone-containing regimen therapy. Radiological findings were also reviewed to assess the role of (18) fluoro-deoxyglucose positron emission tomography in the initial assessment and in the monitoring of this extranodal lymphoma. A high percentage of response was observed: 82.3% of patients achieved a complete response, 11.8% a partial response. Furthermore, a very remarkable progression-free survival (71%) and overall survival (100%) were estimated at 14 years. No relevant toxicities were registered. Our results support the use of fludarabine and mitoxantrone-containing regimens as first-line therapy in the treatment of BALT lymphoma even if further data are necessary to consolidate our findings. Positron emission tomography scanning may provide additional valuable information in the assessment of BALT lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Médula Ósea/patología , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Mitoxantrona/efectos adversos , Cintigrafía , Estudios Retrospectivos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivadosRESUMEN
Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan ((90) Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by (90) Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Quimioterapia de Consolidación , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Tomografía de Emisión de Positrones , Inducción de Remisión , Rituximab/administración & dosificación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
BACKGROUND: The use of (18) F-fluorodeoxyglucose positron-emission tomography (PET) scan has increased considerably in the clinical management of non-Hodgkin lymphoma patients, and its role as a prognostic factor during chemotherapy has been established recently. METHODS: Between May 2003 and May 2009, 91 newly diagnosed patients with primary mediastinal large B-cell lymphoma (PMLBCL) and diffuse large B-cell lymphoma (DLBCL) were treated with 12 weekly cycles of rituximab-MACOP-B (n = 12 patients with PMLBCL), 6 cycles of rituximab-CHOP21 (n = 65 patients with DLBCL, aged < 60 years and 1 patient with PMLBCL), or 8 weekly cycles of rituximab-VNCOP-B (n = 13 DLBCL patients, aged ≥ 60 years). All patients underwent a staging PET examination at baseline and a midtreatment (interim) PET examination after 6 weeks of rituximab-MACOP-B treatment, 3 cycles of rituximab-CHOP21 treatment, or 4 weeks of rituximab-VNCOP-B treatment and again at the end of the chemo-immunotherapy regimen. RESULTS: At midtreatment evaluation, 35 patients showed a persistently positive PET scan; only 6 (17%) of these patients achieved a continuous complete response (CCR). However, 56 patients presented with a negative interim PET, and 50 (89%) of these patients achieved and maintained a CCR. Comparison between the 2 PET groups indicated a statistically significant association between PET findings and event-free survival (P = .0001) and overall survival (P = .0001). CONCLUSIONS: The results of this study indicated that midtreatment PET may represent a significant step forward in helping physicians make crucial decisions on further treatment. Cancer 2011. © 2010 American Cancer Society.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Fluorodesoxiglucosa F18 , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Femenino , Humanos , Leucovorina/administración & dosificación , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Monitoreo Fisiológico/métodos , Invasividad Neoplásica , Estadificación de Neoplasias , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab , Análisis de Supervivencia , Factores de Tiempo , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL. PATIENTS AND METHODS: Between March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m(2)) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months. RESULTS: A total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia. CONCLUSION: Oral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resistencia a Antineoplásicos , Femenino , Humanos , Lenalidomida , Linfoma de Células B Grandes Difuso/patología , Masculino , Recurrencia , Rituximab , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/análogos & derivadosRESUMEN
BACKGROUND: We performed a retrospective investigation to assess the efficacy of chemotherapy and rituximab as front-line treatment for primary bone lymphoma (PBL). PATIENTS AND METHODS: Between 1999 and 2009, 21 previously untreated patients received a diagnosis of PBL. All the patients were treated with anthracycline-containing chemotherapeutic regimens, with the addition of rituximab; 11 patients received consolidative radiation therapy after induction treatment. RESULTS: Patients' median age was 34 years (range, 18-82 years); all presented with diffuse large B-cell lymphoma. Complete responses were seen in 95.2% of the patients treated. No relapses were observed at a median follow-up of 43.9 months. Eight-year overall survival and disease-free survival were 95.2% and 100.0%, respectively. CONCLUSION: These data indicate that the combined chemotherapy plus rituximab treatment may represent a suitable front-line approach in PBL, with a high rate of responses and an excellent long-term survival.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/terapia , Factores Inmunológicos/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/radioterapia , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante/métodos , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de SupervivenciaRESUMEN
BACKGROUND: Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alpha-interferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients. METHODS: The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow-up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front-line therapy, Group B patients (n =53) were treated with 2 lines, Group C patients (n = 34) with 3 lines, Group D patients (n = 17) with 4 lines, and Group E patients (n = 8) with 5 lines. RESULTS: In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years). CONCLUSIONS: This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response.