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1.
Hematol Oncol Stem Cell Ther ; 12(4): 194-203, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31319058

RESUMO

OBJECTIVE/BACKGROUND: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era-that is, in patients treated in induction and rescued only with chemotherapy. METHODS: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). RESULTS: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of <1 year, no differences were observed in 5-year progression-free survival (48% vs. 66%, respectively; p = .44) or in 5-year OS (69% vs. 77%, p = .4). Patients in the ETF cohort transplanted in complete remission showed a plateau in the OS curves, at 56%, beyond 13.7 years of follow-up. CONCLUSION: ASCT may be a curative option for ETF in patients who respond to rescue chemotherapy, without the need for immunotherapy or other therapies, and should be considered as an early consolidation, especially in patients with difficult access to rituximab.

2.
Br J Haematol ; 185(3): 480-491, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30793290

RESUMO

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

4.
Br J Haematol ; 184(5): 797-807, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548583

RESUMO

We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem-cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3-year progression-free survival (PFS). Sixty patients (median age 55 [28-71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9-72) and 14 (4-53) days to achieve neutrophil and platelet counts of >0.5 × 109 /l and >20 × 109 /l, respectively. Non-relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow-up of 67 (40-77) months, the estimated 3-year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12-0.56]) and OS (RR, 0.40 [95% CI 0.17-0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Linfoma/mortalidade , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoenxertos , Cloridrato de Bendamustina/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Podofilotoxina/efeitos adversos , Taxa de Sobrevida
7.
Support Care Cancer ; 26(4): 1253-1264, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29116407

RESUMO

PURPOSE: The purpose of this study was to describe perceptions of fatigue in anemic patients with lymphoma or multiple myeloma (MM). METHODS: This is an observational multicenter study in a prospective cohort of lymphoma and MM patients with hemoglobin ≤ 11 g/dl managed under clinical practice. Fatigue was assessed at baseline and after 3 months using the PERFORM questionnaire, the Functional Assessment of Cancer Therapy-Fatigue, the linear analogue self-assessment, and visual analogue scale (VAS) scales. RESULTS: Two hundred and fifty patients (125 with lymphoma, 125 with MM) were included. Only 59.2 and 56.0% of patients received treatment for anemia, respectively. After 3 months, the hemoglobin levels increased significantly compared to baseline from 10.0 ± 1.2 to 11.5 ± 1.8 in the lymphoma group and from 9.9 ± 0.9 to 10.9 ± 1.5 g/dl, in the MM group (P < 0.001, both comparisons). At baseline, 87.2 and 84.8% of patients had fatigue (median intensity (VAS) 60 and 50). The overall PERFORM score decreased from 35.2 ± 15.2 to 32.0 ± 14.6 (P = 0.048), without differences between groups. No statistically significant changes were observed in the other scales. After multivariable adjustment, the only common independent factor associated to improvements in fatigue and health-related quality-of-life (HRQoL) was an increase in hemoglobin levels. The administration of curative intention treatment was also associated with HRQoL improvements. The psychometric properties of the PERFORM questionnaire in MM patients were good (Cronbach's alpha 0.87-0.98; intraclass correlation coefficients 0.84-0.89; effect sizes 0.59-0.96). CONCLUSIONS: Almost all patients with lymphoma or MM diagnosed with anemia suffered from fatigue of moderate to severe intensity. Despite similar anemia supportive treatment, better correction of fatigue scores was observed in lymphoma patients after 3 months. Increases in hemoglobin were significantly associated to improvements in fatigue and HRQoL.


Assuntos
Anemia/etiologia , Fadiga/etiologia , Linfoma/complicações , Mieloma Múltiplo/complicações , Idoso , Anemia/sangue , Estudos de Coortes , Fadiga/sangue , Feminino , Hemoglobinas/metabolismo , Humanos , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
8.
Cancer Med ; 6(12): 2766-2774, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29076254

RESUMO

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OS-progression-free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression-free at 24 months post-ASCT (26 who died without disease progressions within 24 months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P = 0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9-30.2; P < 0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30 months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P < 0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.


Assuntos
Linfoma Folicular/cirurgia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
9.
Br J Haematol ; 178(5): 699-708, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28782811

RESUMO

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.


Assuntos
Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica/patologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica/efeitos dos fármacos , Progressão da Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Espanha/epidemiologia , Análise de Sobrevida , Adulto Jovem
11.
Clin Nucl Med ; 42(8): 595-602, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28604477

RESUMO

OBJECTIVES: To compare staging correctness between contrast-enhanced FDG PET/ceCT and 64-slice multi-detector-row CT (ceCT64) for initial staging and response evaluation at the end of treatment (EOT) in patients with Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL), and follicular lymphoma. METHODS: This prospective study compared initial staging and response evaluation at EOT. One hundred eighty-one patients were randomly assigned to either ceCT64 or FDG PET/ceCT. A nuclear medicine physician and a radiologist read FDG PET/ceCT scans independently and achieved post hoc consensus, whereas another independent radiologist interpreted ceCT64 separately. The reference standard included all clinical information, all tests, and follow-up. Ethics committees of the participating centers approved the study, and all participants provided written consent. RESULTS: Ninety-one patients were randomized to ceCT64 and 90 to FDG PET/ceCT; 72 had Hodgkin lymphoma, 72 had DLBCL, and 37 had follicular lymphoma. There was excellent correlation between the reference standard and initial staging for both FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84), although evaluation of the response at EOT was excellent only for FDG PET/ceCT (κ = 0.91). CONCLUSIONS: Our study demonstrated satisfactory agreement between FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84) in initial staging compared with the reference standard (P = 0.16). Response evaluation at EOT with FDG PET/ceCT (κ = 0.91) was superior compared with ceCT64 (κ = 0.307) (P < 0.001).


Assuntos
Meios de Contraste , Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Linfoma/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/instrumentação , Estudos Prospectivos , Resultado do Tratamento
12.
Biol Blood Marrow Transplant ; 23(10): 1631-1640, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28533060

RESUMO

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL.


Assuntos
Linfoma Folicular/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária , Recidiva , Sistema de Registros , Estudos Retrospectivos , Rituximab/uso terapêutico , Transplante Autólogo/métodos , Adulto Jovem
13.
Biol Blood Marrow Transplant ; 23(1): 53-59, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27771496

RESUMO

We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m2 i.v. (days -3 and -2) plus melphalan 70 mg/m2 i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/terapia , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Células B/mortalidade , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Radioimunoterapia/métodos , Radioimunoterapia/mortalidade , Terapia de Salvação/mortalidade , Análise de Sobrevida , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Radioisótopos de Ítrio/uso terapêutico
15.
Br J Haematol ; 167(3): 327-36, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25066542

RESUMO

We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Prednisona/administração & dosagem , Prognóstico , Estudos Prospectivos , Indução de Remissão , Rituximab , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
16.
Br J Haematol ; 164(5): 668-74, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24274082

RESUMO

The use of highly effective rituximab-containing therapy for treating diffuse large B-cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem-cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre-treated with rituximab as part of first-line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R- group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age-adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R- patients, those in the R+ group had a significantly better progression-free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B-cell lymphoma pre-treated with first-line rituximab-containing therapy than in rituximab-naive patients.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Transplante de Medula Óssea , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab , Terapia de Salvação/métodos , Resultado do Tratamento , Adulto Jovem
17.
Lancet Haematol ; 1(3): e104-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27029228

RESUMO

BACKGROUND: No standard first-line systemic treatment for mucosa-associated lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to assess the safety and activity of a response-adapted combination of bendamustine plus rituximab as upfront treatment for this type of lymphoma. METHODS: In a multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with MALT lymphoma at any site and stage and treated them with bendamustine (90 mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks. Inclusion criteria were measurable or evaluable disease, age 18-85 years, and unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising in the stomach after failure of Helicobacter pylori eradication and primary cutaneous cases after failure of local therapies. Exclusion criteria included evidence of histological transformation, CNS involvement, and active hepatitis B or C virus or HIV infection. After three cycles, patients achieving complete response received one additional cycle (total four cycles) and those achieving partial response received three additional cycles (total six cycles). The primary endpoint was 2-year event-free survival. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01015248. FINDINGS: 60 patients from 19 centres in Spain were enrolled between May 27, 2009, and May 23, 2011, and received treatment; 57 patients were evaluable for the primary endpoint. Only 14 (25%) patients needed more than four cycles of treatment. After a median follow-up of 43 months (IQR 37-51), median event-free survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97) and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4 adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile neutropenia or infections were reported in three (5%) and four (7%) patients, respectively. INTERPRETATION: This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma. FUNDING: Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.

18.
Haematologica ; 98(10): 1563-70, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23753021

RESUMO

UNLABELLED: The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with (90)Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of (90)Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with (90)Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. TRIAL REGISTRATION: clinical.gov identifier: NCT2005-004400-37.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Linfoma de Célula do Manto/diagnóstico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Rituximab , Resultado do Tratamento
20.
Haematologica ; 98(3): 357-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23065525

RESUMO

This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in 67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).


Assuntos
Antineoplásicos/uso terapêutico , Depsipeptídeos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Depsipeptídeos/farmacologia , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Recidiva , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Adulto Jovem
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