RESUMEN
Post-transplant lymphoproliferative disorder (PTLD) may arise after solid organ transplantation, and the most common subtype resembles diffuse large B cell lymphoma (DLBCL). In DLBCL-type PTLD, the anti-CD20 antibody rituximab (R) may be combined with chemotherapy (R-CHOP) or use a strategy (R-primary; similar to the PTLD-1 clinical trial) consisting of induction with four weekly doses of R-alone, without any chemotherapy or sequential R-CHOP follow-up. Here we report on a multicentre retrospective cohort of solid organ transplant patients with DLBCL-type PTLD that were treated with R. In 168 adults, two-year overall survival (OS) was 63·7% [95% CI (confidence interval) 56·6-71·7%]. No difference in OS was observed, whether patients were treated with R-CHOP versus the R-primary strategy. In the 109 patients treated with R-primary, multivariate analysis found that baseline IPI score and the response to R-induction predicted OS. Patients who responded to R-induction had durable remissions without the addition of chemotherapy. Conversely, of the 46 patients who had stable or progressive disease after R-induction (R-failure), those who received R-CHOP had an only marginally improved outcome, with a two-year OS of 45% (23·1-65·3%) vs. no R-CHOP at 32% (14·7-49·8%). In real-world patients, R-failure and high IPI scores predict a poor outcome in DLBCL-type PTLD.
Asunto(s)
Linfoma de Células B Grandes Difuso , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias , Rituximab , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Prednisona/administración & dosificación , Prednisona/efectos adversos , Estudios Retrospectivos , Rituximab/administración & dosificación , Rituximab/efectos adversos , Tasa de Supervivencia , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalin-fixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater). With a median follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7% vs 2.2%; P = .001). Patients with activated B-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, in multivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC(+) BCL2(+) DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies.
Asunto(s)
Biomarcadores de Tumor/análisis , Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-myc/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linaje de la Célula , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Recurrencia , Riesgo , Rituximab/administración & dosificación , Análisis de Matrices Tisulares , Translocación Genética , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
OPINION STATEMENT: Central nervous system (CNS) relapse is an undesirable event in the course of patients with diffuse large B cell lymphoma (DLBCL) with a median survival of approximately 6 months following CNS relapse. CNS prophylaxis for the prevention of CNS recurrence, in addition to the standard R-CHOP chemotherapy, is thus preferable. For an overall relapse risk of 2-5%, administration of CNS-directed therapies for all patients with DLBCL is unnecessary and prophylaxis should be targeted for the high-risk patients. CNS-International Prognostic Index (CNS-IPI) score has enabled risk stratification with risk ranging < 1% (low-risk group) compared to > 10% (high-risk group). The latter could be considered for CNS prophylaxis. CNS-IPI, however, is not perfect and may not capture patients with high-risk extra-nodal sites such as testicular DLBCL. Cell-of-origin and MYC/BCL2 expression can further build on CNS-IPI to narrow higher risk patients. CNS prophylaxis strategies are controversial. Common strategies include intrathecal (IT) chemotherapy and systemic CNS penetrants such as methotrexate. IT chemotherapy does not adequately penetrate the brain parenchyma and hence it is insufficient in preventing parenchymal CNS recurrences. Most experts promote systemic methotrexate for high-risk groups, which penetrates both the leptomeningeal and parenchymal CNS compartments. Even though systemic CNS prophylaxis is widely promoted over IT alone, its efficacy is unclear. Ongoing efforts in search for appropriate CNS prophylaxis strategies are warranted. My personal practice is to administer systemic high-dose methotrexate in conjunction with R-CHOP chemotherapy for eligible patients deemed at a high risk of CNS recurrence, especially those with high-risk CNS-IPI and extra-nodal involvement.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/secundario , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/patología , Prednisona/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Rituximab , Vincristina/uso terapéuticoRESUMEN
The addition of rituximab (R) to chemotherapy improves outcomes in patients with systemic B-cell non-Hodgkin lymphomas, but the impact in patients with primary central nervous system lymphoma (PCNSL) receiving high-dose methotrexate (HDMTX) is unknown. Patients diagnosed with PCNSL at the British Columbia Cancer Agency (BCCA) between 2000 and 2013 were treated with ≥1 cycle of HDMTX 8 g/m(2) every 2 weeks, to best response or 10 cycles. After 2006, rituximab 375 mg/m(2) was given every 2 weeks with HDMTX for a total of 4 doses. 49 (66%) patients received HDMTX alone and 25 (34%) HDMTX+R, with a median of 5 (range 1-10) HDMTX cycles, and no difference between groups. The median follow-up was 5 years: 8.8 years (range 3.15-13.5 years) HDMTX and 1.9 years (range 0.5-7 years) HDMTX+R. The 5-year PFS was 17%, with no difference between groups (HR: 0.75, 95% CI: 0.41-1.35; P = 0.33). The 5-year OS was 38%, with no difference between the groups OS (HR: 0.73, 95% CI: 0.35-1.52; P = 0.39). In this retrospective study comparing two subgroups of patients treated in different eras, the addition of R to HDMTX did not appear to improve outcomes in PCNSL, possibly consistent with its known poor CNS penetration. It is possible that with a larger sample size, longer follow-up, or different rituximab dosing/schedule, the addition of rituximab may lead to a statistically significant improvement in outcomes. Prospective randomized trials currently in progress will more definitively estimate the impact of the addition of rituximab to HDMTX-based chemotherapy for PCNSL.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/uso terapéutico , Rituximab/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Rituximab/administración & dosificación , Adulto JovenRESUMEN
Febrile neutropenia (FN) is a common complication of cancer therapy. It can contribute to delays in treatment, increased rates of hospitalization, and severe infections. FN may also hinder completion of intended chemotherapy. Granulocyte colony stimulating factors (G-CSF) lower the rates of FN, infections, and hospitalization. Multiple national and international guidelines advocate the use of G-CSF in primary prophylaxis if the overall risk of FN is >20% (accounting for both patient and treatment-related risks). Lymphoma specific guidelines recommend G-CSF use in similar fashion. However, based on our updated review of published literature, we note that primary prophylaxis (PP) with G-CSF fails to improve overall survival as well as infection-related mortality. Moreover, lymphoma specific cost-effectiveness analyses on the use of PP have shed further doubt on the optimal use of this myeloid growth factor. In this general review, we will discuss whether PP with GCSF has any role in the management of adults with non-Hodgkin lymphoma.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfoma/prevención & control , Anciano , Femenino , Humanos , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana EdadAsunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/secundario , Linfoma de Células B Grandes Difuso/patología , Modelos Estadísticos , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica , Biopsia , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Ciclofosfamida , Doxorrubicina , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona , Pronóstico , Medición de Riesgo , Rituximab , Resultado del Tratamiento , VincristinaAsunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia de Inducción/métodos , Linfoma de Células B/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Rituximab/administración & dosificación , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B/diagnóstico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
Management practices in early-stage (I/II) follicular lymphoma (FL) are variable and include radiation (RT), systemic therapy, or combined modality therapy (CMT). There is a paucity of data regarding maintenance rituximab in this cohort. We conducted an international retrospective study of patients with newly diagnosed early-stage FL staged with positron emission tomography (PET)-computed tomography and bone marrow biopsy. Three hundred sixty-five patients (stage I, n = 221), median age 63 years, treated from 2005-2017 were included, with a median follow-up of 45 months. Management included watchful waiting (WW; n = 85) and active treatment (n = 280). The latter consisted of RT alone (n = 171) or systemic therapy (immunochemotherapy [n = 63] or CMT [n = 46]). Forty-nine systemically treated patients received maintenance rituximab; 72.7% of stage I patients received RT alone, compared to 42.6% with stage II (P < .001). Active therapies yielded comparable overall response rates (P = .87). RT alone and systemic therapy without maintenance rituximab yielded similar progression-free survival (PFS) (hazard ratio [HR], 1.32; 95% confidence interval [CI], 0.77-2.34; P = .96). Maintenance rituximab improved PFS (HR, 0.24; 95% CI, 0.095-0.64; P = .017). The incidence of transformation was lower with systemic therapy compared to RT or WW (HR, 0.20; 95% CI, 0.070-0.61; P = .034). Overall survival was similar among all practices, including WW (P = .40). In the largest comparative assessment of management practices in the modern era, variable practices each resulted in similar excellent outcomes. Randomized studies are required to determine the optimal treatment in early-stage FL.
Asunto(s)
Linfoma Folicular/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
PURPOSE: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. METHODS: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. RESULTS: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). CONCLUSIONS: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Our case highlights that cardiac lymphoma may mimic amyloid infiltration of the myocardium on cardiac magnetic resonance (CMR), and is a particularly challenging diagnosis in the setting of transformed Waldenström's macroglobulinemia. Heightened suspicion and early diagnosis of cardiac lymphoma is paramount as chemotherapy has been demonstrated to portent an increased survival rate.
RESUMEN
PURPOSE: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. RESULTS: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. CONCLUSION: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.