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1.
Ann Oncol ; 29(8): 1822-1827, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897404

RESUMO

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Progressão da Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Adulto Jovem
3.
Ann Oncol ; 28(7): 1436-1447, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28379322

RESUMO

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Tomografia por Emissão de Pósitrons/normas , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/normas , Antineoplásicos/efeitos adversos , Consenso , Meios de Contraste/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Fluordesoxiglucose F18/administração & dosagem , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
4.
Ann Oncol ; 27(10): 1922-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27502701

RESUMO

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Biomarcadores Tumorais , Meios de Contraste/administração & dosagem , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia
5.
Ann Oncol ; 27(3): 390-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26681685

RESUMO

BACKGROUND: Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy improves response rates and survival in patients with B-cell non-Hodgkin lymphoma (NHL). However, rituximab induces a transient B-cell depletion and a dose-dependent T-cell inactivation that could impair T-cell immunosurveillance. The impact of rituximab on second primary malignancy (SPM) risk remains unclear so far. We thus carried out a systematic review to compare SPM risk among patients treated or not with rituximab. PATIENTS AND METHODS: We retrieved trials from MEDLINE and EMBASE and updated data presented at American Society of Hematology and American Society of Clinical Oncology meetings from 1998 to 2013. We selected randomized, controlled trials addressing newly or relapsed/progressive B-cell NHL in which randomization arms differed only from rituximab administration. Two authors extracted data and assessed the study quality. RESULTS: We analyzed nine trials involving 4621 patients. At a median follow-up of 73 months, a total of 169 SPMs were observed in patients randomized to rituximab compared with 165 SPMs in patients not randomized to rituximab (OR = 0.88; 95% CI 0.66-1.19). The proportion of females, histology subtypes, use of rituximab in first line or in maintenance did not influence SPM risk (P = 0.94, P = 0.80, P = 0.87, P = 0.87, respectively). Cumulative exposure through prolonged administration in trials with rituximab maintenance did not contribute to an increased risk of SPM (P = 0.86). CONCLUSION: Our meta-analysis suggests no SPM predisposition among NHL survivors exposed to rituximab at a median follow-up of 6 years.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Segunda Neoplasia Primária/induzido quimicamente , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade
6.
Ann Oncol ; 26(4): 774-779, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25605745

RESUMO

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory end point in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL. PATIENTS AND METHODS: Patients received romidepsin at a dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary end point was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by International Workshop Criteria (IWC) using conventional radiology. For the exploratory PET end point, patients with at least baseline FDG-PET scans were assessed by IWC + PET criteria. RESULTS: Of 130 patients, 110 had baseline FDG-PET scans, and 105 were PET positive at baseline. The use of IWC + PET criteria increased the objective response rate to 30% compared with 26% by conventional radiology. Durations of response were well differentiated by both conventional radiology response criteria [CR/CRu versus partial response (PR), P = 0.0001] and PET status (negative versus positive, P < 0.0001). Patients who achieved CR/CRu had prolonged progression-free survival (PFS, median 25.9 months) compared with other response groups (P = 0.0007). Patients who achieved PR or stable disease (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P = 0.6427). When grouping PR and SD patients by PET status, patients with PET-negative versus PET-positive disease had a median PFS of 18.2 versus 7.1 months (P = 0.0923). CONCLUSIONS: Routine use of FDG-PET does not obviate conventional staging, but may aid in determining prognosis and refine response assessments for patients with PTCL, particularly for those who do not achieve CR/CRu by conventional staging. The optimal way to incorporate FDG-PET scans for patients with PTCL remains to be determined. TRIAL REGISTRATION: NCT00426764.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Depsipeptídeos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluordesoxiglucose F18/farmacocinética , Linfoma de Células T Periférico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Seguimentos , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Indução de Remissão , Taxa de Sobrevida , Distribuição Tecidual
7.
Transfus Apher Sci ; 50(2): 294-302, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24462181

RESUMO

Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (p<0.0001) and their respective shares remained stable throughout the BV processes (p non-significant). We analysed the role of intrinsic (patient's features) and extrinsic (features before starting leukapheresis sessions) factors in collections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our results suggested that the main factors likely to influence intended HSC collections or unintended mature cell harvests were pre-leukapheresis blood cell levels. Our model was meant to assist apheresis teams in analysing shares of HSC collected and mature cells harvested with new devices or with new types of HSC mobilization.


Assuntos
Células-Tronco Hematopoéticas/citologia , Leucaférese/métodos , Leucaférese/normas , Modelos Teóricos , Adolescente , Adulto , Idoso , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Estudos Prospectivos
8.
Hum Reprod ; 29(3): 525-33, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24345581

RESUMO

STUDY QUESTION: How does the successful cryopreservation of semen affect the odds of post-treatment fatherhood among Hodgkin lymphoma (HL) survivors? SUMMARY ANSWER: Among 334 survivors who wanted to have children, the availability of cryopreserved semen doubled the odds of post-treatment fatherhood. WHAT IS KNOWN ALREADY: Cryopreservation of semen is the easiest, safest and most accessible way to safeguard fertility in male patients facing cancer treatment. Little is known about what proportion of patients achieve successful semen cryopreservation. To our knowledge, neither the factors which influence the occurrence of semen cryopreservation nor the rates of fatherhood after semen has been cryopreserved have been analysed before. STUDY DESIGN, SIZE, DURATION: This is a cohort study with nested case-control analyses of consecutive Hodgkin survivors treated between 1974 and 2004 in multi-centre randomized controlled trials. A written questionnaire was developed and sent to 1849 male survivors. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine hundred and two survivors provided analysable answers. The median age at treatment was 31 years. The median follow-up after cryopreservation was 13 years (range 5-36). MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and sixty-three out of 902 men (40%) cryopreserved semen before the start of potentially gonadotoxic treatment. The likelihood of semen cryopreservation was influenced by age, treatment period, disease stage, treatment modality and education level. Seventy eight of 363 men (21%) used their cryopreserved semen. Men treated between 1994 and 2004 had significantly lower odds of cryopreserved semen use compared with those treated earlier, whereas alkylating or second-line (chemo)therapy significantly increased the odds of use; no other influencing factors were identified. We found an adjusted odds ratio of 2.03 (95% confidence interval 1.11-3.73, P = 0.02) for post-treatment fatherhood if semen cryopreservation was performed. Forty-eight out of 258 men (19%) who had children after HL treatment became a father using cryopreserved semen. LIMITATIONS, REASONS FOR CAUTION: Data came from questionnaires and so this study potentially suffers from response bias. We could not perform an analysis with correction for duration of follow-up or provide an actuarial use rate due to lack of dates of semen utilization. We do not have detailed information on either the techniques used in cryopreserved semen utilization or the number of cycles needed. STUDY FUNDING/COMPETING INTERESTS: Lance Armstrong Foundation, Dutch Cancer Foundation, René Vogels Stichting, no competing interests.


Assuntos
Criopreservação , Fertilidade , Doença de Hodgkin/terapia , Preservação do Sêmen , Sêmen , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Estudos de Coortes , Doença de Hodgkin/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Sobreviventes
10.
Ann Oncol ; 24(4): 1032-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23235801

RESUMO

BACKGROUND: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. PATIENTS AND METHODS: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. RESULTS: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). CONCLUSION: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab , Resultado do Tratamento , Vindesina/administração & dosagem , Vindesina/efeitos adversos
11.
N Engl J Med ; 367(6): 520-31, 2012 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-22873532

RESUMO

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Análise de Intenção de Tratamento , Linfoma de Célula do Manto/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Indução de Remissão , Rituximab , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vincristina/efeitos adversos , Vincristina/uso terapêutico
12.
Rev Mal Respir ; 27(5): 500-4, 2010 May.
Artigo em Francês | MEDLINE | ID: mdl-20569884

RESUMO

UNLABELLED: A 71 year-old man with primary Sjögren's syndrome developed pulmonary opacities within two years of the diagnosis. Videothoracoscopic lung biopsy demonstrated high grade, B-cell, CD20+, large-cell lymphoma, associated with Epstein-Barr virus (RNA EBERs of the virus were expressed by the lymphoma cells). The condition initially improved with rituximab-CHOP treatment, but recurrence of the lymphoma was fatal. CONCLUSION: High-grade B-cell lymphoma associated with EBV can occur in Sjögren's syndrome in the absence of long-term immunosuppressive therapy.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Neoplasias Pulmonares/virologia , Linfoma de Células B/virologia , Síndrome de Sjogren/complicações , Idoso , Humanos , Masculino
13.
Ann Oncol ; 21(9): 1870-1876, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20157180

RESUMO

BACKGROUND: Ocrelizumab is a humanized anti-CD20 antibody with increased antibody-dependent cellular cytotoxicity compared with rituximab. This phase I/II study evaluated its safety and efficacy in patients with relapsed/refractory follicular lymphoma (FL) after prior rituximab therapy. DESIGN AND METHODS: Forty-seven patients were treated in three dose cohorts and received eight infusions every 3 weeks: cohort A, 200 mg/m(2) (n = 15); cohort B, 375 mg/m(2) (n = 16); cohort C, first dose 375 mg/m(2), seven subsequent doses of 750 mg/m(2) (n = 16). Patients were assessed for safety, efficacy, pharmacodynamics and pharmacokinetics. RESULTS: The median patient age was 58 years, the majority had Ann Arbor stage III/IV disease and had received a median of 2 (range 1-6) prior regimens. Ocrelizumab was well tolerated with grade 3/4 toxicity occurring in 9% of patients. The most common toxicity was infusion-related reactions (74% patients), all grade 1/2 except one grade 3 event. The objective response rate was 38% and was similar in patients with low-affinity and high-affinity variants of the Fcgamma receptor IIIa (FcgammaRIIIa). With follow-up of approximately 28 months, the median progression-free survival was 11.4 months. CONCLUSION: Ocrelizumab demonstrated activity in patients with relapsed/refractory FL following prior rituximab treatment, with safety similar to rituximab although adverse events appeared milder.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma Folicular/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Feminino , Seguimentos , Humanos , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
14.
Ann Oncol ; 21(4): 842-850, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19914958

RESUMO

BACKGROUND: This prospective multicentric phase II study aimed to confirm the results of the C5R protocol of high-dose methotrexate (MTX)-based chemotherapy (CT) for immunocompetent primary central nervous system lymphoma. PATIENTS AND METHODS: A total of 99 patients received age-adapted CT (C5R protocol) followed by radiotherapy. Patients younger than 61 years (group 1, n = 45) received the full C5R with MTX, doxorubicin, vincristine, cyclophosphamide, and cytarabine. Patients aged 61-70 years (group 2, n = 36) received reduced doses. Patients older than 70 years (group 3, n = 18) received four courses of MTX, cyclophosphamide, and etoposide. RESULTS: Median age was 63 years and 51% of patients had performance status of more than one. Seventeen patients died of toxicity during CT. Complete response was achieved in 56%, 53%, and 28% of patients in groups 1, 2, and 3, respectively. With a median follow-up of 83 months, the 5-year progression-free survival was 31%, 28%, and 11% and the 5-year overall survival 42%, 31%, and 17% for groups 1, 2, and 3, respectively. Leukoencephalopathy occurred in 32% of assessable patients, in both group 1 and groups 2-3. CONCLUSION: The C5R protocol was feasible in the multicentric setting with favorable long-term survival in patients younger than 60 years. Despite dose adaptation, results in older patients were disappointing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Linfoma/mortalidade , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Sociedades Médicas , Fatores de Tempo , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
15.
Ann Oncol ; 20(12): 1985-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19567453

RESUMO

BACKGROUND: This study compared the induction regimens doxorubicin, cyclophosphamide and etoposide (ACE) with doxorubicin, cyclophosphamide, vincristine, bleomycin and prednisone (ACVBP) before high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) for patients with poor-risk diffuse large B-cell lymphoma (DLBCL). A second randomisation compared rituximab with observation post-ASCT. MATERIALS AND METHODS: Four hundred and seventy-six patients <60 years old with newly diagnosed CD20+ DLBCL were randomised to induction with ACE or ACVBP. Three hundred and thirty responders received HDT followed by ASCT. After ASCT, 269 patients were re-randomised to receive either maintenance rituximab or observation alone. Randomisation was stratified by the quality of response to ASCT. The primary end point of this study was event-free survival (EFS). RESULTS: At a median of 4 years' follow-up from the second randomisation, there was a trend (P = 0.1) towards increased EFS for patients who received rituximab compared with observation. CONCLUSION: The type of induction therapy (ACVBP or ACE) did not significantly affect overall survival at a median 51 months' follow-up.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Bleomicina/uso terapêutico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento , Vindesina/uso terapêutico , Adulto Jovem
16.
Ann Dermatol Venereol ; 135(11): 748-52, 2008 Nov.
Artigo em Francês | MEDLINE | ID: mdl-19061653

RESUMO

BACKGROUND: No histological or clinical criteria allow distinction between primary cutaneous marginal zone B-cell lymphoma (MZL) and secondary cutaneous forms of systemic marginal zone B-cell lymphoma. Consequently, staging alone can indicate the origin of lymphoma. Lymphoma is considered as primary cutaneous only if no other extracutaneous sites are found. We studied the histological appearance of 49 cutaneous lymphomas in order to find distinctive criteria indicative of an extracutaneous origin. MATERIALS AND METHODS: This was a retrospective descriptive study of histological appearance for 49 patients with cutaneous marginal lymphoma: 29 cases of the primary form and 20 cases with extracutaneous involvement. RESULTS: Comparison of histological criteria did not reveal any differences between the primary cutaneous form and others forms. No prognostic criteria for relapse were found. DISCUSSION: A cutaneous tropism of primary MZL suggested the hypothesis of specific cutaneous receptors on B-cells that could have led to different histological appearances depending on the origin of the lymphoma. However, our study did not confirm this hypothesis.


Assuntos
Rearranjo Gênico , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Humanos , Fenótipo , Prognóstico , Estudos Retrospectivos
17.
Leukemia ; 22(10): 1917-24, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18615101

RESUMO

Gene expression profiles have been associated with clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with rituximab (R)-CHOP in the Groupe d'Etude des Lymphomes de l'Adulte clinical centers. We used this data set to select transcripts showing an association with progression-free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative reverse transcription-PCR in the 23 R-CHOP samples of the screening set and an additional 44 R-CHOP samples set to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell-of-origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising four genes of the cell-of-origin signature (LMO2, MME, LPP and FOXP1) and two genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Perfilação da Expressão Gênica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Desaminase APOBEC-3G , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Ciclofosfamida/administração & dosagem , Citidina Desaminase/genética , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a DNA/genética , Doxorrubicina/administração & dosagem , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Proteínas com Domínio LIM , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Metaloproteínas/genética , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/administração & dosagem , Proteínas Proto-Oncogênicas , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rituximab , Vincristina/administração & dosagem , Proteínas rab de Ligação ao GTP/genética
19.
Ann Oncol ; 19(5): 964-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18296419

RESUMO

BACKGROUND: Vorinostat has demonstrated activity in refractory cutaneous T-cell lymphoma. In a phase I trial, an encouraging activity in diffuse large-B-cell lymphoma (DLBCL) was noted. PATIENTS AND METHODS: We carried out a phase II trial (NCT00097929) of oral vorinostat 300 mg b.i.d. (14 days/3 weeks or 3 days/week) in patients with measurable, relapsed DLBCL who had received two or more systemic therapies. Response rate and duration (DOR), time to progression (TTP) and safety were assessed. RESULTS: Eighteen patients were enrolled (median age: 66 years; median prior therapies: 2). Seven received 300 mg b.i.d. 14 days/3 weeks, but four had grade 3 or 4 toxicity (dose-limiting toxicity, DLT). The schedule was amended to 300 mg b.i.d. 3 days/week), and none had DLT. One achieved a complete response (TtR = 85 days; DOR =or >468 days) and one had stable disease (301 days). Sixteen discontinued for progressive disease; median TTP was 44 days. Median number of cycles was 2 (1 to >19). Common drug-related adverse experiences (AEs; mostly grade 1/2) were diarrhea, fatigue, nausea, anemia and vomiting. Three patients had dose reduction; none discontinued for drug-related AEs. Drug-related AE >or=grade 3 included thrombocytopenia (16.7%) and asthenia (11.1%). CONCLUSION: Vorinostat was well tolerated at 300 mg b.i.d. 3 days/week or 200 mg b.i.d. 14 days/3 weeks but had limited activity against relapsed DLBCL.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Linfoma Difuso de Grandes Células B/enzimologia , Masculino , Pessoa de Meia-Idade , Recidiva , Espasmo/induzido quimicamente , Trombocitopenia/induzido quimicamente , Vorinostat
20.
Leukemia ; 22(3): 487-95, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18094718

RESUMO

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are proposed for diagnosis, differential diagnosis, staging, prognostic factors, treatment and response criteria. The guidelines proposed here are intended to contribute to the standardization of the diagnosis and treatment of these patients, and should facilitate the future development of clinical trials that could define more precisely predictive markers for histological progression or lack of response, and evaluate new drugs or treatments.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Biomarcadores Tumorais/sangue , Medula Óssea/patologia , Aberrações Cromossômicas , Terapia Combinada , Comorbidade , Diagnóstico Diferencial , Gerenciamento Clínico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imunofenotipagem , Linfoma de Zona Marginal Tipo Células B/sangue , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto , Prognóstico , Rituximab , Baço/patologia , Esplenectomia , Neoplasias Esplênicas/sangue , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia
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