RESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) and statin drugs may protect against the development of non-Hodgkin lymphoma (NHL), but data are limited, particularly for NHL subtypes. Furthermore, some in vitro, animal and epidemiologic data suggest there may be a synergistic effect of these two agents, but there has been no test of this hypothesis in NHL. We evaluated the self-reported use of NSAIDs and statins in a clinic-based study of 1703 NHL patients and 2199 frequency-matched controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding variables. We observed an inverse association of regular use of low-dose aspirin with risk of NHL (OR = 0.82; 95% CI 0.70-0.96) that was stronger with longer duration of use (P < .01). There were no associations for use of regular or extra-strength aspirin, ibuprofen, other NSAIDs, statins or other cholesterol-lowering drugs with NHL risk, while an inverse association with COX-2 inhibitors was equivocal. There was also no interaction of low-dose aspirin and statins on NHL risk. Inverse associations of similar magnitude to all NHL were observed for regular use of low-dose aspirin with diffuse large B-cell, follicular, marginal zone and all other lymphomas, although not all associations were statistically significant. In conclusion, low-dose aspirin but not regular/extra strength aspirin, other NSAIDs or statin use was associated with lower risk of NHL. Beyond the potential for the primary prevention of NHL, these data also point to a role of anti-platelet or other effects of low-dose aspirin in lymphomagenesis that warrant follow-up.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Incidência , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Standard bone marrow biopsy (BMB) and bone involvement with follicular lymphoma (FL) on positron emission tomography (PET)/computed tomography (CT) both predict early clinical failure in FL. The key clinical question is whether PET/CT findings can obviate the need for BMB. The goal of this study was to determine the value of PET/CT in determining bone involvement in FL, using posterior iliac crest BMB as the gold standard. MATERIALS AND METHODS: A total of 548 patients with newly diagnosed grade 1-3A FL were included. The presence, pattern, and location of bone involvement, spleen involvement, and standardized uptake values (SUVs) in the L3 vertebral body were recorded for all patients and compared with the BMB report. RESULTS: Excluding patients with focal bone lesions on PET/CT, the sensitivity and specificity of PET/CT in detecting bone or marrow involvement, compared with BMB, were 53% and 88%, respectively. The sensitivity and specificity of spleen involvement on PET/CT in predicting a positive BMB were 55% and 86%, respectively. An L3 SUVmax of less than 2.0 resulted in a negative predictive value (NPV) of 96% for marrow involvement on BMB; an L3 SUVmean below 1.4 resulted in an NPV of 100%. CONCLUSION: In newly diagnosed FL, PET/CT-detected bone and splenic involvement is highly specific for a positive BMB, and very low SUV values (<2.0 SUVmax and < 1.4 SUVmean ) in the lumbar spine have a high NPV for a negative BMB. Routine BMB may be obviated in these patients. BMB remains necessary to definitively exclude bone marrow involvement in a large majority of patients with a negative PET. IMPLICATIONS FOR PRACTICE: Predicting early clinical failure in follicular lymphoma (FL) is important but difficult. Bone marrow involvement by FL is associated with early clinical failure, and determining this involvement is a key component of the initial staging. This study highlights that in certain patients, positron emission tomography/computed tomography is sufficient in determining bone or marrow involvement, without the need for a confirmatory bone marrow biopsy (BMB). An algorithm is provided based on these findings to help clinicians determine which patients would benefit from BMB and when it can be avoided.
Assuntos
Medula Óssea , Linfoma Folicular , Biópsia , Medula Óssea/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Linfoma Folicular/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin, and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from 3 clinical trials and a population-based registry. HGBL-DH/TH made up 7.9% of the DLBCL, confined primarily to the germinal center B-cell-like (GCB; 13.3%) compared with activated B-cell-like (ABC; 1.7%) subtype (P < .001). HGBL-DH/TH with BCL2 rearrangement is a GCB phenomenon with no cases observed in 415 ABC DLBCL. A screening strategy restricting FISH testing to tumors of GCB subtype (by Lymph2Cx or Hans IHC) plus dual protein expression of MYC and BCL2 by IHC could limit testing to 11% to 14% of tumors, with a positive predictive value of 30% to 37%; however, this strategy would miss approximately one-quarter of tumors with HBGL-DH/TH with BCL2 rearrangement and one-third of all HGBL-DH/TH. These results provide accurate estimation of the proportion of HGBL-DH/TH among tumors with DLBCL morphology and allow determination of the impact of various methods available to screen DLBCL tumors for FISH testing.
Assuntos
Rearranjo Gênico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Linhagem Celular Tumoral , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Gradação de TumoresRESUMO
PURPOSE: We aimed to describe the clinical and histologic findings in a few enucleation cases with intraocular lymphoma. METHODS: Retrospective review of pathology files from a 22-year period identified cases with intraocular lymphoma among all enucleation specimens. Patient demographics, clinical findings, laboratory results, radiographic studies, and indication for enucleation were abstracted from electronic health records; slides were reviewed. RESULTS: Four patients (three women and one man; age range, sixth through eighth decades of life) underwent enucleation with a final diagnosis of intraocular lymphoma. Two patients with primary vitreoretinal large B-cell lymphomas had been treated for refractory uveitis. Specimens showed retinal and subretinal infiltrates by atypical large B-lymphocytes and rare neoplastic cells in the vitreous. The remaining two patients had systemic lymphoproliferative disorders. One patient had chronic lymphocytic leukemia and floaters in his eye; vitreoretinal lymphoma developed, consistent with intraocular Richter transformation. The other had diffuse large B-cell lymphoma in remission; however, blurred vision developed, she was treated for panuveitis without improvement, and was later found to have ocular involvement by diffuse large B-cell lymphoma. CONCLUSION: Our series details the unusual circumstances when an eye is removed for intraocular lymphoma. Different patterns of ocular tissue involvement were observed when we compared primary and secondary lymphomas.
Assuntos
Enucleação Ocular/métodos , Linfoma Intraocular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Retina/patologia , Neoplasias da Retina/diagnóstico , Tomografia de Coerência Óptica/métodos , Corpo Vítreo/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Linfoma Intraocular/cirurgia , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias da Retina/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodosRESUMO
Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. This study aimed to determine the incidence and patterns of extranodal (EN) and spleen disease using PET/CT, and assess their utility in predicting early clinical failure. PET/CT images from 613 cases of untreated FL (2003-2016) were reviewed. The location and number of EN sites, patterns of bone involvement, and splenic involvement were recorded. Outcomes were assessed using event-free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24). So, 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. The presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. Presence of ≥2 EN sites and bone involvement pattern were also predictive of OS in a univariate analysis. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (HR 1.49 (1.11-2.00), P = .007; HR 1.71 (1.10-2.65), P = .017; and HR 1.67 (1.06-2.62), P = .026, respectively). When the multivariate analysis was performed using PRIMA-PI factors (marrow and B2M), the number of EN sites was an independent prognostic factor for inferior OS (HR 2.28; P = .05). Baseline PET/CT identifies EN involvement in nearly half of patients with untreated FL. The presence of ≥2 EN sites, bone, soft tissue, or splenic involvement predicts early clinical failure. These results, when combined with other factors, may better identify high-risk patients and guide therapy.
Assuntos
Fluordesoxiglucose F18/administração & dosagem , Linfoma Folicular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Baço/diagnóstico por imagem , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively. Among primary and concurrent VRL, median failure free survival (FFS), CNS relapse-free survival (CNS-RFS) and overall survival (OS) were: 1.8, 4.9, and 4.1 years, respectively; among PVRL, median FFS, CNS-RFS, and OS were: 2.6 year, Not Reached and 9.3 year, respectively. No CNS relapse occurred beyond 4 years in PVRL. Median OS for patients diagnosed between 1990 and 1999 vs between 2000 and 2018 was 1.5 vs 9.4 years, respectively (P = .0002). OS was significantly higher in PVRL, as compared with concurrent VRL (P = .04). Previous immunosuppression and poor performance status were predictive of worse outcome. In PVRL, a combined systemic and intraocular therapy showed higher FFS (P = .002) and CNS-RFS (P = .003), but no differences in OS. Among 18 secondary VRL, at a median follow-up of 1.1 year after vitreoretinal relapse, median FFS and OS were 0.3 and 1.3 years. An improvement in survival of VRL has been observed over the decades. PVRL should undergo combined systemic and intraocular chemotherapy to prevent CNS progression.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Terapia Combinada/métodos , Linfoma/terapia , Metotrexato/uso terapêutico , Neoplasias da Retina/terapia , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Raios gama/uso terapêutico , Humanos , Injeções Intravenosas , Injeções Intravítreas , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Retina/efeitos dos fármacos , Retina/patologia , Retina/efeitos da radiação , Neoplasias da Retina/mortalidade , Neoplasias da Retina/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/patologia , Corpo Vítreo/efeitos da radiaçãoRESUMO
A number of reports have shown a propensity of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) to transform into diffuse large B-cell lymphoma (DLBCL). Long-term data on the incidence and outcomes of transformed NLPHL are lacking. A comprehensive analysis of the actively maintained Mayo Clinic Lymphoma Database was performed. Between 1970 and 2011, 222 consecutive adult patients with new untreated NLPHL were identified. Median age at diagnosis was 40 years, and 146 (66%) were males. The median follow-up was 16 years. Seventeen patients (7.6%) developed a transformation to DLBCL. The median time to transformation was 35 months (range, 6-268 months). Based on the observed 17 transformations during 2304 patient-years of follow-up, the rate of transformation was 0.74 per 100 patient-years. In a multivariate analysis, use of any prior chemotherapy ( ITALIC! P= .04) and splenic involvement ( ITALIC! P= .03) were significantly associated with increased risk of transformation. The 5-year overall survival (OS) in those with transformed disease was 76.4%, and transformation did not adversely affect OS when compared with patients who did not experience transformation. In this large single-institution cohort with long-term follow-up, the risk of transformation was lower than that observed in other low-grade lymphomas.
Assuntos
Linfócitos B/patologia , Transformação Celular Neoplásica/patologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto JovemRESUMO
High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double-/triple-hit lymphoma) have an aggressive clinical course. We investigated the prognostic value of transformation from low-grade lymphoma, cytological features (high grade versus large cell), MYC rearrangement partners (immunoglobulin versus nonimmunoglobulin gene), and treatment. We evaluated 100 adults with double-/triple-hit lymphoma, reviewing cytological features; cell of origin; and rearrangements of MYC, BCL2, and BCL6 using MYC, BCL2, and BCL6 break-apart and IGH/MYC, IGL/MYC, IGK/MYC, and IGH/BCL2 dual-fusion interphase fluorescence in situ hybridization probes. Outcome analysis was restricted to patients with lymphoma, de novo or at transformation, who received anthracycline-based chemotherapy. Among them, 60% had high-grade cytological features; 91% had a germinal center B-cell phenotype, and 60% had a MYC/IG rearrangement. Germinal center B-cell phenotype was associated with BCL2 rearrangements (P<0.001). Mean (95% confidence interval) 5-year overall survival was 49% (37%-64%). Transformation from previously treated and untreated low-grade lymphoma was associated with inferior overall survival (hazard ratio, 2.99; P=0.008). Patients with high-grade cytological features showed a non-significant tendency to inferior outcome (hazard ratio, 2.32; P=0.09). No association was observed between MYC rearrangement partner and overall survival (hazard ratio, 1.00; P=0.99). Compared with patients receiving rituximab, cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate/ifosfamide, etoposide, and cytarabine (R-CODOX-M/IVAC) had a non-significant tendency to better overall survival (hazard ratio, 0.37; P=0.10). In conclusion, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements had heterogeneous outcomes and MYC/IG rearrangements were not associated with inferior overall survival.
Assuntos
Rearranjo Gênico , Imunoglobulinas/genética , Linfoma Difuso de Grandes Células B , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
Our aim was to evaluate whether quality of life (QOL) scores at diagnosis predict survival among patients with aggressive lymphoma. Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE and systematically followed for event-free and overall survival (OS). QOL was measured with the Functional Assessment of Cancer Treatment-General (FACT-G), which measures 4 domains: physical, social/family, emotional, and functional well-being (WB); a single item Linear Analogue Self-Assessment (LASA) measuring overall QOL; and a spiritual WB LASA. From 9/2002 to 12/2009, 701 patients with aggressive lymphoma who completed baseline QOL questionnaires were enrolled. At a median follow-up of 71 months (range 6-128), 316 patients (45%) had an event and 228 patients (33%) died. All baseline QOL measures but emotional WB were significantly associated with OS (all P < 0.04); of which all but LASA spiritual remained significant after adjusting for IPI and NHL subtype. The strongest associations were with total FACT-G (adjusted HR = 0.86, 95% CI: 0.79-0.94, P = 0.00062) and functional WB (adjusted HR = 0.88, 95% CI: 0.83-0.93, P < .0001). QOL LASA was associated with OS (adjusted HR = 0.92, 95% CI: 0.87-0.97, P = 0.0041). Patients with clinically deficient QOL (overall QOL ≤50) had a median OS of 92 months compared with 121 months for patients with QOL >50 (P = 0.0004). In this large sample of patients with aggressive lymphoma, we found that baseline QOL is independently predictive of OS. QOL should be assessed as a prognostic factor in patients with aggressive lymphoma.
Assuntos
Linfoma/diagnóstico , Linfoma/mortalidade , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Adulto JovemRESUMO
Cutaneous reactions to red tattoo pigment rarely manifest as pseudolymphomatous reactions. We describe an exceedingly rare case of red tattoo-related T-cell predominant pseudolymphoma microscopically mimicking mycosis fungoides. Careful clinicopathological correlation was required to obtain the correct diagnosis and aid in an effective treatment course.
Assuntos
Tinta , Pseudolinfoma/induzido quimicamente , Dermatopatias/induzido quimicamente , Tatuagem/efeitos adversos , Linfócitos T CD8-Positivos/imunologia , Corantes/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pseudolinfoma/imunologia , Dermatopatias/imunologiaRESUMO
Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.
Assuntos
Leucemia Mieloide Aguda/etiologia , Linfoma Folicular/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Radioimunoterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Radioimunoterapia/métodos , Fatores de Risco , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto Jovem , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS.
Assuntos
Quimiocina CXCL9/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Linfoma Folicular/sangue , Linfoma Folicular/diagnóstico , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Rituximab , Adulto JovemRESUMO
Follicular lymphoma (FL), an indolent neoplasm caused by a t(14;18) chromosomal translocation that juxtaposes the BCL2 gene and immunoglobulin locus, has a variable clinical course and frequently undergoes transformation to an aggressive lymphoma. Although BCL2 mutations have been previously described, their relationship to FL progression remains unclear. In this study, we evaluated the frequency and nature of BCL2 mutations in 2 independent cohorts of grade 1 and 2 FLs, along with the correlation between BCL2 mutations, transformation risk, and survival. The prevalence of BCL2 coding sequence mutations was 12% in FL at diagnosis and 53% at transformation (P < .0001). The presence of these BCL2 mutations at diagnosis correlated with an increased risk of transformation (hazard ratio 3.6; 95% CI, 2.0-6.2; P < .0001) and increased risk of death due to lymphoma (median survival of 9.5 years with BCL2 mutations vs 20.4 years without; P = .012). In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited enhanced antiapoptotic capacity in vitro. Accordingly, BCL2 mutations can affect antiapoptotic Bcl-2 function, are associated with increased activation-induced cytidine deaminase expression, and correlate with increased risk of transformation and death due to lymphoma.
Assuntos
Transformação Celular Neoplásica/genética , Linfoma Folicular/genética , Linfoma Folicular/mortalidade , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/metabolismo , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Estudos de Coortes , Citidina Desaminase/biossíntese , Citidina Desaminase/genética , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade , Prevalência , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Risco , Taxa de SobrevidaRESUMO
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day-cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single-agent everolimus in this patient population. Fifty-five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33-85) with a median of five prior therapies (range: 1-10). The ORR was 35% (19/55; 95% CI: 24-48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4-14.1), median duration of response of 11.5 months (95%-CI: 5.7-30.4), and a median progression-free survival of 7.2 months (95%-CI: 5.5-12.5). The most common toxicity was hematologic with grades 3-4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non-Hodgkin lymphoma patients and is well tolerated.
Assuntos
Everolimo/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Intervalo Livre de Doença , Everolimo/efeitos adversos , Feminino , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/mortalidade , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Pessoa de Meia-Idade , Complexos Multiproteicos/antagonistas & inibidores , Neutropenia/induzido quimicamente , Indução de Remissão , Terapia de Salvação/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.
Assuntos
Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Fosfatases de Especificidade Dupla/genética , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Fatores Reguladores de Interferon/genética , Estimativa de Kaplan-Meier , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Prognóstico , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1-3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. OS was compared to age-and-sex-matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78-4.88; Lyon SMR = 8.74, 95%CI: 5.41-13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56-0.94, Lyon SMR = 1.02, 95%CI: 0.58-1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97-25.02, Lyon SMR = 19.10, 95%CI:9.86-33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31-17.74, Lyon SMR = 7.22, 95%CI:4.13-11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096-1101, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Linfoma Folicular/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Diagnóstico Precoce , Feminino , Humanos , Imunoterapia , Linfoma Folicular/epidemiologia , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12-88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps.
Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Modelos Estatísticos , Medicina de Precisão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Adulto JovemAssuntos
Neoplasias Ósseas , Linfoma Folicular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Feminino , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de ProgressãoRESUMO
INTRODUCTION: Neurolymphomatosis (NL) is a rare disorder characterized by invasion of cranial or peripheral nerves, nerve roots, or plexi, usually by aggressive subtypes of non-Hodgkin lymphoma (NHL). The most common clinical presentation is that of a painful polyneuropathy or polyradiculopathy, followed by cranial neuropathy and, less frequently, by painless polyneuropathy. METHODS: Clinical and pathologic findings are reported for 2 NL cases. RESULTS: The following 2 patients with NL, with disparate clinical presentations, are presented: a patient with subacute onset, painful, multifocal, mixed axonal and demyelinating radiculoplexus neuropathy due to a large B-cell NHL, who required 2 targeted fascicular nerve biopsies to demonstrate NL; and a patient with a slowly progressive, length-dependent axonal polyneuropathy due to a low-grade B-cell lymphoproliferative disorder, as shown on a diagnostic sural nerve biopsy. CONCLUSIONS: The cases described illustrate the wide clinical spectrum of NL.
Assuntos
Linfoma Difuso de Grandes Células B/patologia , Progressão da Doença , Humanos , Linfoma Difuso de Grandes Células B/fisiopatologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias do Sistema Nervoso Periférico/fisiopatologia , Nervo Isquiático/patologiaRESUMO
The World Health Organization classification of non-Hodgkin lymphoma (NHL) was introduced in 2001. However, its incorporation into clinical practice is not well-described. We studied the distribution of NHL subtypes in adults diagnosed from 1998 to 2011, evaluated time trends, geo-demographic correlates, and changes in 5-year overall survival (OS). We obtained data prospectively collected by the National Cancer Data Base, which covers 70% of US cancer cases. There were 596,476 patients diagnosed with NHL. The major subtypes were diffuse large B-cell (32.5%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18.6%), follicular (17.1%), marginal zone (8.3%), mantle cell (4.1%), peripheral T-cell not-otherwise-specified (1.7%), Burkitt (1.6%), hairy cell (1.1%), lymphoplasmacytic (1.1%), and NHL not-otherwise-specified (10.8%). Over the study period, the proportion of NHL not-otherwise-specified declined by half, while marginal zone lymphoma doubled. The distribution of major and rare NHL subtypes varied according to demographics but less so geographically or by type of treatment facility. We noted several novel findings among Hispanics (lower proportion of CLL/SLL, but higher Burkitt lymphoma and nasal NK/T-cell lymphoma), Asians (higher enteropathy-associated T-cell and angioimmunoblastic T-cell lymphomas), Blacks (higher hepatosplenic T-cell lymphoma), and Native Americans (similar proportions of CLL/SLL and nasal NK/T-cell lymphoma as Asians). With the exception of peripheral T-cell not-otherwise-specified and hairy cell leukemia, 5-year OS has improved for all the major NHL subtypes.