RESUMO
The addition of rituximab has improved outcomes in diffuse large B-cell lymphoma (DLBCL), however, there remains limited information on the impact of rituximab in those with testicular involvement. All patients with diffuse large cell lymphoma and testicular involvement treated with curative intent were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. In total, 134 patients diagnosed between 1982 and 2015 with diffuse large cell lymphoma involving the testis were identified: 61 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy and 73 received CHOP plus rituximab (R-CHOP). A greater proportion of R-CHOP treated patients had higher International Prognostic Index (IPI, P = 0·005). In multivariate analysis, the protective effect of rituximab on progression-free survival (hazard ratio (HR) 0·42, P < 0·001), overall survival (HR 0·39, P < 0·001) and cumulative incidence of progression (HR 0·46, P = 0·014) were independent of the IPI. However, in a competing risk multivariate analysis including central nervous system (CNS) prophylaxis and the CNS-IPI, rituximab was not associated with a decreased risk of CNS relapse. The addition of rituximab has reduced the risk of lymphoma recurrence in testicular DLBCL, presumably through improved eradication of systemic disease. However, CNS relapse risk remains high and further studies evaluating effective prophylactic strategies are needed.
Assuntos
Linfoma Difuso de Grandes Células B/patologia , Rituximab/uso terapêutico , Neoplasias Testiculares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colúmbia Britânica , Neoplasias do Sistema Nervoso Central/prevenção & controle , Neoplasias do Sistema Nervoso Central/secundário , Ciclofosfamida/uso terapêutico , Bases de Dados Factuais , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Profilaxia Pré-Exposição/tendências , Prednisona/uso terapêutico , Prognóstico , Recidiva , Risco , Rituximab/farmacologia , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty-seven patients were identified with a male predominance (n = 31, 66%), median age of 64 years and predominantly limited stage (n = 40, 85%). Median follow-up was 8·4 years. The 5-year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5-year disease-specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as-treated analysis, the 5-year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5-year TTP favoured RT (82% vs. 33%, P = 0·004). The 5-year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/terapia , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica , Terapia Combinada/métodos , Terapia Combinada/mortalidade , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Anaplásico Cutâneo Primário de Células Grandes/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL.
Assuntos
Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non-Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10-year overall survival for first-line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26-0·88, P = 0·017]. The 10-year failure-free survival (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28-0·80, P = 0·004). Among the 38 patients who received first-line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31-1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10-year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/terapia , Esplenectomia , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: We examined the relationship between location of residence at the time of diagnosis of diffuse large B-cell lymphoma (DLBCL) and health outcomes in a geographically large Canadian province with publicly funded, universally available medical care. PATIENTS AND METHODS: The British Columbia Cancer Registry was used to identify all patients 18-80 years of age diagnosed with DLBCL between January 2003 and December 2008. Home and treatment center postal codes were used to determine urban versus rural status and driving distance to access treatment. RESULTS: We identified 1,357 patients. The median age was 64 years (range: 18-80 years), 59% were male, 50% were stage III/IV, 84% received chemotherapy with curative intent, and 32% received radiotherapy. There were 186 (14%) who resided in rural areas, 141 (10%) in small urban areas, 183 (14%) in medium urban areas, and 847 (62%) in large urban areas. Patient and treatment characteristics were similar regardless of location. Five-year overall survival (OS) was 62% for patients in rural areas, 44% in small urban areas, 53% in medium urban areas, and 60% in large urban areas (p = .018). In multivariate analysis, there was no difference in OS between rural and large urban area patients (hazard ratio [HR]: 1.0; 95% confidence interval [CI]: 0.7-1.4), although patients in small urban areas (HR: 1.4; 95% CI: 1.0-2.0) and medium urban areas (HR: 1.4; 95% CI: 1.0-1.9) had worse OS than those in large urban areas. CONCLUSION: Place of residence at diagnosis is associated with survival of patients with DLBCL in British Columbia, Canada. Rural patients have similar survival to those in large urban areas, whereas patients living in small and medium urban areas experience worse outcomes.
Assuntos
Disparidades em Assistência à Saúde/estatística & dados numéricos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica/epidemiologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemAssuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Linfoma Difuso de Grandes Células B/patologia , Modelos Estatísticos , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Biópsia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona , Prognóstico , Medição de Risco , Rituximab , Resultado do Tratamento , VincristinaRESUMO
Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P = .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/CD8 were significant for progression-free survival (PFS; P = .056), CD25 for both PFS and OS (P = .002 and P = .024, respectively), and FOXP3(+) predicted PFS, OS, and RT (P = .001, P < .001 and p = .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3(+) pattern were independent predictors of OS (P = .008 and P < .001, respectively), while only FOXP3(+) pattern predicted RT (P = .004). We conclude that FOXP3(+) cell distribution significantly predicts survival and RT in FL.
Assuntos
Transformação Celular Neoplásica/imunologia , Fatores de Transcrição Forkhead/imunologia , Linfoma Folicular/imunologia , Linfócitos T Reguladores/imunologia , Antígenos CD , Relação CD4-CD8 , Transformação Celular Neoplásica/metabolismo , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/biossíntese , Humanos , Linfoma Folicular/sangue , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Masculino , Taxa de Sobrevida , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologiaRESUMO
BCL2 and MYC are oncogenes commonly deregulated in lymphomas. Concurrent BCL2 and MYC translocations (BCL2(+)/MYC(+)) were identified in 54 samples by karyotype and/or fluorescence in situ hybridization with the aim of correlating clinical and cytogenetic characteristics to overall survival. BCL2(+)/MYC(+) lymphomas were diagnosed as B-cell lymphoma unclassifiable (BCLU; n = 36) with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL); DLBCL (n = 17), or follicular lymphoma (n = 1). Despite the presence of a t(14;18), 5 cases were BCL2 protein-negative. Nonimmunoglobulin gene/MYC (non-IG/MYC) translocations occurred in 24 of 54 cases (44%) and were highly associated with DLBCL morphology (P < .001). Over a median follow-up of 5.3 years, 6 patients remained in remission and 32 died within 6 months of the MYC(+) rearrangement, irrespective of whether MYC(+) occurred at diagnosis (31 of 54) or transformation (23 of 54; P = .53). A non-IG/MYC translocation partner, absent BCL2 protein expression and treatment with rituximab-based chemotherapy, were associated with a more favorable outcome, but a low International Prognostic Index score and DLBCL morphology were independent predictors of overall survival. A comprehensive cytogenetic analysis of BCL2 and MYC status on all aggressive lymphomas may identify a group of high-risk patients who may benefit from chemotherapeutic regimens that include rituximab and/or BCL2-targeted therapy.
Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidade , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/metabolismo , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/metabolismo , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Estudos Retrospectivos , Rituximab , Taxa de SobrevidaRESUMO
Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 2:1 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.
Assuntos
Antraciclinas , Linfoma Difuso de Grandes Células B , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Contraindicações , Ciclofosfamida/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Patients with metastatic melanoma typically have a poor outcome; however, a small proportion of patients achieve long-term survival (LTS). It is unclear how often LTS is related to sensitivity to chemotherapy. METHODS: All patients with metastatic melanoma treated with either dacarbazine (DTIC) or temozolomide (TMZ) at the British Columbia Cancer Agency (BCCA) from January 1, 1988 to February 1, 2006 were identified through the BCCA pharmacy electronic database, which was then linked to the surveillance and outcomes unit to identify patients with LTS, defined as survival > or =18 months following chemotherapy. RESULTS: In total, 397 patients were treated with either DTIC (n = 349) or TMZ (n = 48) and 43 patients (10.8%) were identified with LTS. Two additional patients with LTS were added prior to 1988 for a total of 45 patients. The 5-year overall and progression-free survival rates for patients with LTS were 33% and 16%, respectively. In total, 16% had a complete response (CR) to chemotherapy, which was the only factor identified that correlated with survival in the multivariate analysis. However, most patients with LTS had an incomplete response to chemotherapy. CONCLUSIONS: LTS occurs in select patients who achieve a CR to chemotherapy. However, this occurs in only a minority of patients and, in most cases, the longer survival is likely the result of indolent disease biology or host factors.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Indução de Remissão , Neoplasias Cutâneas/secundário , Análise de Sobrevida , Sobreviventes , Temozolomida , Resultado do Tratamento , Adulto JovemRESUMO
Molecular mechanisms responsible for lymphoma resistance to apoptosis often involve the bcl-2 pathway. In this study, we investigated the cell signaling pathways activated in bcl-2-overexpressing human mantle cell lymphoma cell lines (JVM-2 and Z-138) that have been treated with oblimersen, a molecular gene silencing strategy that effectively suppresses bcl-2 in vitro and in vivo. Z-138 cells expressed higher levels of bcl-2 and were more sensitive to the effects of bcl-2 silencing, mediated by oblimersen or bcl-2 small interfering RNA, in vitro. Tumors derived following injection of Z-138 cells were sensitive to oblimersen as judged by decreases in tumor growth rate and decreases in cell proliferation (as measured by Ki-67). Immunohistochemistry and Western blot analysis of oblimersen-treated Z-138 tumors revealed a dose-dependent decrease in bcl-2 levels and an associated increase in the proapoptotic proteins caspase-3 and caspase-9. Silencing bcl-2 in Z-138 xenografts revealed an associated dose-dependent suppression of bax, a decrease in nuclear factor-kappaB and phospho-nuclear factor-kappaB, and transient loss of p53 levels. Coimmunoprecipitation studies suggest that the latter observation is mediated by an association between bcl-2 and phospho-mdm2. Bcl-2 silencing also led to p27 down-regulation and coimmunoprecipitation studies point to a role for bcl-2 in regulation of p27 localization/degradation. Bcl-2 silencing was also correlated with loss of cyclin D1a protein levels but not cyclin D1b levels. Coimmunoprecipitation studies indicate that bcl-2 may mediate its effects on cyclin D1a via interaction with p38 mitogen-activated protein kinase as well as a previously unreported interaction between bcl-2 and cyclin D1a.
Assuntos
Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Inativação Gênica , Linfoma de Célula do Manto/genética , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Apoptose/fisiologia , Western Blotting , Proliferação de Células , Ciclina D , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Proteínas de Ligação a DNA/fisiologia , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/prevenção & controle , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas de Neoplasias/genética , Oligonucleotídeos Antissenso/farmacologia , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tionucleotídeos/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Various methods have been explored to enhance antibody-based cancer therapy. The use of multivalent antibodies or fragments against tumor antigens has generated a great deal of interest, as various cellular signals, including induction of apoptosis, inhibition of cell growth/survival, or internalization of the surface molecules, can be triggered or enhanced on extensive cross-linking of the target/antibody complex by the multivalent form of the antibody. The goal of the studies reported here was to develop multivalent antibody constructs via grafting of antibody molecules onto liposome membranes to enhance antibody activity. Using trastuzumab and rituximab as examples, up to a 25-fold increase in the antibody potency in cell viability assay was observed when the antibodies were presented in the multivalent liposome formulation. Key cell survival signaling molecules, such as phosphorylated Akt and phosphorylated p65 nuclear factor-kappaB, were down-regulated on treatment with multivalent liposomal trastuzumab and liposomal rituximab, respectively. Potent in vivo antitumor activity was shown for liposomal trastuzumab. The data presented here showed the potential of liposome technology to enhance the therapeutic effect of antibodies via a mechanism that modulates cell survival through clustering of the target/antibody complex.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Animais , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Murinos , Anticorpos Antineoplásicos , Antígenos CD20/imunologia , Antígenos de Neoplasias/imunologia , Western Blotting , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Regulação para Baixo , Feminino , Citometria de Fluxo , Genes erbB-2/genética , Genes erbB-2/imunologia , Humanos , Lipossomos , Camundongos , Camundongos Knockout , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/imunologia , Rituximab , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , TrastuzumabRESUMO
BCL-2 protein expression correlates with shorter survival in patients with diffuse large B cell lymphoma (DLBCL) who are treated with CHOP chemotherapy. We report a retrospective analysis of the prognostic significance of BCL-2 status in patients who received CHOP with the addition of rituximab (CHOP-R) for DLBCL. Patients over 15 years of age with de novo, HIV negative DLBCL, without CNS involvement, and known BCL-2 protein status were identified from the BCCA Lymphoid Cancer Database. BCL-2 tumour positivity was defined as over 50% of tumour cells with BCL-2 protein expression. 140 patients who received CHOP-R were analysed. The majority (59%) of patients were over 60 years of age. Disease stage distribution was limited (22%) and advanced (78%). BCL-2 protein expression was observed in 90 (64%) cases. IPI score was similar in both BCL-2 positive and negative cases. Median follow-up time for living patients is 40 months. BCL-2 status did not predict for either progression-free or overall survival. IPI score was predictive for progression-free survival but not overall survival. The addition of rituximab to CHOP chemotherapy negates the adverse prognostic influence of BCL-2 protein expression on progression free and overall survival in DLBCL.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Genes bcl-2 , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Biomarcadores Tumorais/genética , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Regulação Leucêmica da Expressão Gênica , Humanos , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino , Desoxicitidina/análogos & derivados , Dexametasona , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença de Hodgkin/mortalidade , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Retratamento , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento , Adulto Jovem , GencitabinaRESUMO
PURPOSE: For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). METHODS: We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with "B" symptoms or bulky [> 10 cm] disease) DLBCL. RESULTS: A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. CONCLUSION: The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Colúmbia Britânica , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
The objectives of this study were foremost to further characterize pre-existing cell lines containing the t(11;14)(q13;q32) translocation. This translocation along with cyclin D1 overexpression is characteristic of Mantle Cell Lymphoma (MCL), an aggressive B cell neoplasm. Considerable variation in the abundance of cyclin D1 expression was observed. mRNA levels were examined by RT-PCR as differences in cyclin D1 mRNA abundance have been shown to synergize with INK4A/Arf deletions to dictate proliferation rate and survival in MCL patient samples. In this study, the cell lines, Z-138 and HBL-2, which exhibited the fastest growth rates and the shortest survival times in Rag2-M mice, had high expression of either one or both cyclin D1 mRNA isoforms and had negligible expression of p16. On the other hand, NCEB-1 and JVM-2 had low expression of both mRNA isoforms, retained p16 expression, and had slower growth rates and exhibited longer survival times in Rag2-M mice. Furthermore, JVM-2, which was found to have the lowest expression of cyclin D1, was the only cell line that expressed cyclin D2. The results of the characterization of Z-138, HBL-2, NCEB-1 and JVM-2 reveal that this group of cell lines represents both classic and variant features of MCL.
Assuntos
Cromossomos Humanos Par 11 , Linfoma de Célula do Manto/genética , Translocação Genética , Animais , Sequência de Bases , Western Blotting , Linhagem Celular Tumoral , Ciclina D1/genética , Primers do DNA , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/virologia , Masculino , Camundongos , Reação em Cadeia da Polimerase , RNA Mensageiro/genéticaRESUMO
Although it is generally regarded appropriate to start chemotherapy promptly after a diagnosis of diffuse large B-cell lymphoma (DLBCL), the optimal time from diagnosis to treatment (TDT) is unknown. A total of 689 patients diagnosed with DLBCL and treated with ≥ 1 cycle of CHOP-R with curative intent during 2003-2008 in British Columbia were identified: 347 (50%) TDT ≤ 4 weeks, 277 (40%) TDT 5-8 weeks, 65 (10%) TDT > 8 weeks. For the respective TDT groups, 5-year OS estimates were 61%, 74%, 63% (p = 0.006); 5-year PFS 57%, 70%, 61% (p = 0.006); and 5-year DSS 64%, 80%, 77% (p <0.001). In multivariate analysis, TDT >8 weeks was associated with worse OS (HR 1.20 (95% CI 1.03, 1.41), p = 0.020), PFS (HR 1.33 (95% CI 1.15, 1.54), p < 0.001), and DSS (HR 1.40 (95% CI 1.10, 1.78), p = 0.006). Clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.
RESUMO
The impact of treatment delays on outcomes in Hodgkin lymphoma (HL) is currently unknown. Time from definitive histologic diagnosis to first ABVD treatment (TDT) was calculated in 810 adults with HL: 365 (45%) TDT ≤4 weeks, 369 (46%) TDT 5-8 weeks, 76 (9%) TDT >8 weeks. The 5-year overall survival (OS) was 92% TDT ≤4 weeks, 92% TDT 5-8 weeks, and 83% TDT >8 weeks (p = 0.007). The 5-year disease-specific survival (DSS) was 93% TDT ≤4 weeks, 95% TDT 5-8 weeks, and 87% TDT >8 weeks (p = 0.094). The 5-year progression-free survival (PFS) was similar between groups (p = 0.139). In the multivariate analysis, TDT >8 weeks was not associated with worse OS, DSS, or PFS. Despite the univariate association between initiation of ABVD >8 weeks and worse OS, these data do not support such cut-off to improve outcomes. Nevertheless, clinicians should make every effort possible to initiate curative-intent chemotherapy as soon as a diagnosis of HL is established.
Assuntos
Doença de Hodgkin/epidemiologia , Tempo para o Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colúmbia Britânica , Causas de Morte , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). METHODS: The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period-generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. RESULTS: One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. CONCLUSION: Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.
Assuntos
Doença de Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Recidiva , RiscoRESUMO
PURPOSE: To evaluate clinical outcome of patients with limited-stage diffuse large-cell lymphoma (DLCL) treated with three cycles of chemotherapy followed by involved-region irradiation (IRRT). PATIENTS AND METHODS: Adults with limited-stage DLCL were treated with brief doxorubicin-containing chemotherapy regimens between 1980 and 1998. IRRT was administered 3 to 4 weeks after the third chemotherapy treatment in a dose equivalent to 30 Gy in 10 fractions. RESULTS: Three hundred and eight patients (median age, 64 years) were included, and 299 experienced complete remission. After a median follow-up of 86 months, 64 patients developed progressive disease, and 104 patients died (43 from lymphoma, three from toxicity, and 58 from other causes). Actuarial overall and progression-free survival (PFS) rates were, respectively, 80% and 81% at 5 years and 63% and 74% at 10 years. For subgroups identified using the Miller modification of the International Prognostic Index (IPI), the overall survival rates at 5 and 10 years were, respectively, 97% and 89% (no factors), 77% and 56% (one or two factors), and 58% and 48% (three or four factors), and the 5-year and 10-year PFS rates were, respectively, 94% and 89% (no factors), 79% and 73% (one or two factors), and 60% and 50% (three or four factors). Men with testicular presentation, had a definitely inferior outcome. CONCLUSION: Long-term outcome with three cycles of doxorubicin-based chemotherapy and IRRT confirms that this is a successful approach for the majority of patients with limited-stage DLCL. Subgroups with worse prognoses can be identified, and these patients should be offered alternative treatment approaches.