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Background: Chimeric antigen receptor T (CART) cell therapy targeting the B cell specific differentiation antigen CD19 has shown clinical efficacy in a subset of relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. Despite this heterogeneous response, blood pre-infusion biomarkers predicting responsiveness to CART cell therapy are currently understudied. Methods: Blood cell and serum markers, along with clinical data of DLBCL patients who were scheduled for CART cell therapy were evaluated to search for biomarkers predicting CART cell responsiveness. Findings: Compared to healthy controls (n=24), DLBCL patients (n=33) showed significant lymphopenia, due to low CD3+CD4+ T helper and CD3-CD56+ NK cell counts, while cytotoxic CD3+CD8+ T cell counts were similar. Although lymphopenic, DLBCL patients had significantly more activated HLA-DR+ (P=0.005) blood T cells and a higher frequency of differentiated CD3+CD27-CD28- (28.7 ± 19.0% versus 6.6 ± 5.8%; P<0.001) T cells. Twenty-six patients were infused with CART cells (median 81 days after leukapheresis) and were analyzed for the overall response (OR) 3 months later. Univariate and multivariate regression analyses showed that low levels of differentiated CD3+CD27-CD28- T cells (23.3 ± 19.3% versus 35.1 ± 18.0%) were independently associated with OR. This association was even more pronounced when patients were stratified for complete remission (CR versus non-CR: 13.7 ± 11.7% versus 37.7 ± 17.4%, P=0.001). A cut-off value of ≤ 18% of CD3+CD27-CD28- T cells predicted CR at 12 months with high accuracy (P<0.001). In vitro, CD3+CD8+CD27-CD28- compared to CD3+CD8+CD27+CD28+ CART cells displayed similar CD19+ target cell-specific cytotoxicity, but were hypoproliferative and produced less cytotoxic cytokines (IFN-γ and TNF-α). CD3+CD8+ T cells outperformed CD3+CD4+ T cells 3- to 6-fold in terms of their ability to kill CD19+ target cells. Interpretation: Low frequency of differentiated CD3+CD27-CD28- T cells at leukapheresis represents a novel pre-infusion blood biomarker predicting a favorable response to CART cell treatment in r/r DLBCL patients.
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Antígenos CD28 , Linfoma de Células B Grandes Difuso , Humanos , Linfocitos T CD8-positivos , Diferenciación Celular , Antígenos CD19 , Linfoma de Células B Grandes Difuso/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.
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Neoplasias Hematológicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Austria , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Medicina de Precisión , Supervivencia sin Progresión , Adulto JovenRESUMEN
BACKGROUND: Pathogen inactivation (PI) techniques for platelet concentrates (PCs) are one of the latest innovations to improve blood safety and reduce the risk of transfusion-transmitted infections (TTIs). An impaired function and in vivo recovery of platelets as well as an increased PC demand are concerns regarding these techniques. The intent of this study was to evaluate the hemostatic effect of PCs treated with the Intercept™ System by thromboelastometry (TEM) and to assess the clinical validity of its results in comparison to post-transfusion increase (PTI) and corrected count increment (CCI). STUDY-DESIGN AND METHODS: This prospective-observational study included 47 patients (m:f = 25:22; median age: 54 years [21-70]) of our Bone Marrow Transplantation unit with hemato-oncological malignancies transfused with Intercept™-treated PCs. Serial TEM measurements were performed just before and 1 hour after PC transfusion and were analyzed for their correlation with PTI and CCI as well as for clinical variables. RESULTS: The majority of our patients had received a hematopoietic stem cell transplantation (HSCT) (n = 41; 87%). In median 9 (1-50) PCs were transfused. Serial TEM, PTI, and CCI measurements were available for 150 transfusion episodes. The median platelet dose transfused was 2.65 × 1011 /unit (1.8-6). The median CCI was 9.250 (0-28.000). We observed a significant improvement in TEM parameters (p < 0.05) after transfusion of PI PCs, which did not mandatory correlate with the 1-hour PTI and CCI. CONCLUSION: Serial TEM measurements indicate the hemostatic effect of Intercept™-treated PCs. The 1-hour PTI and CCI may not appropriately reflect the in vivo function of platelets after PI PC transfusion.
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Plaquetas/metabolismo , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Transfusión de Plaquetas , Pruebas en el Punto de Atención , Tromboelastografía , Adulto , Anciano , Aloinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/terapia , Estudios ProspectivosRESUMEN
Graft-versus-host disease (GVHD) is the leading cause of mortality after hematopoietic stem cell transplantation and primarily affects barrier organs such as the skin. One-third of cases are refractory to steroid treatment resulting in poor outcomes and the need for novel therapies. Longitudinal analysis of T-cell transcriptomes in patients before the appearance of GVHD symptoms revealed the upregulation of anti-apoptotic regulator B-cell lymphoma 2 (BCL2) at GVHD initiation. To determine the potential of BCL2 inhibition in active GVHD, we analyzed tissues of 88 patients with acute or chronic GVHD. BCL2 RNA was elevated in multiple organs affected by GVHD and expression correlated with transplant-related mortality and steroid-refractory GVHD. BCL2-expressing lymphocytes were present in skin lesions and peripheral blood of patients with acute and chronic GVHD. Inhibition of BCL2 increased the CD4 to CD8 ratio in allogeneic T cells in vitro and induced apoptosis of T cells from patients with steroid-pretreated chronic GVHD ex vivo. In addition, the higher ratio of regulatory to nonregulatory T cells upon blockage of BCL2 could add to the anti-inflammatory effect of BCL2 blockage. Collectively, our results highlight BCL2 as an important factor for GVHD development and introduce BCL2 inhibition as previously unreported and urgently needed targeted therapy in the treatment of steroid-refractory GVHD.
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Corticoesteroides/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Adulto , Apoptosis , Enfermedad Injerto contra Huésped/etiología , Humanos , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transcripción GenéticaRESUMEN
The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death. Multivariate analysis identified six independent factors associated with overall survival (OS) and time-to-first treatment (TTFT): del(17p), unmutated IGHV, del(11q), ß2-microglobulin >3.5 mg/dL, lymphocyte doubling time (LDT) <12 months, and age >60 years. These factors were integrated into the CLL1-PM, which stratified patients into four risk groups. The CLL1-PM was prognostic for OS and TTFT, e.g., the risk of treatment at 5 years was 85.9, 51.8, 27.6, and 11.3% for very low (0-1.5), low (2-4), high (4.5-6.5), and very high-risk (7-14) scores, respectively (P < 0.001). Notably, in addition to factors comprising CLL-IPI, we substantiated del(11q) and LDT as prognostic factors in early CLL. Altogether, our findings would be useful to effectively stratify Binet stage A patients, particularly within the scope of clinical trials evaluating novel agents.
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Biomarcadores de Tumor/genética , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Mutación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Tiempo de TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inmunoterapia/mortalidad , Leucemia Linfocítica Crónica de Células B/mortalidad , Obesidad/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Clorhidrato de Bendamustina/administración & dosificación , Ensayos Clínicos Fase III como Asunto , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Rituximab/administración & dosificación , Factores Sexuales , Tasa de Supervivencia , Vidarabina/administración & dosificaciónRESUMEN
Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy.
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NEW WHO CLASSIFICATION 2016 FOR LYMPHOMA AND MOLECULAR MARKER: The new WHO 2016 Classification for Lymphomas included more detailed definitions of individual entities, such as: the Anaplastic Large Cell Lymphoma, ALK; the terminus of enteropathy-associated T-cell lymphoma (EATCL, type 1) now is restricted to celiac-associated form. The integration of next Generation sequencing (NGS) enables better differential diagnostics, e.âg. angioimmunoblastic lymphoma (AITL) can be characterized by the presence of TET2, RHOA, IDH2 or DNMT3A mutations. Furthermore, certain mutations also have prognostic impact. In ALCL/ALK-, evidence of a DUSP22â/âIRF4 re-arrangement is associated with a better and detection of TP63 is associated with a worse prognosis. CLINICAL COURSE AND PROGNOSIS: In addition to B symptoms and nodal manifestation, extranodal manifestations such as skin infiltrates can be observed in up to 20â%. In AITL, polyclonal hypergammaglobulinemia, Coombs-positive hemolytic anemia and immunodeficiency can occur, as a sign of a dysregulated immune system. ADVANCES IN THERAPY: By combining the immunoconjugate brentuximab-vedotin with chemotherapy, improvement in disease-free and overall survival in CD30+-PTCL (especially in ALCL) was observed. FUTURE PERSPECTIVE: At present demethylating agent 5-azacytidine is explored in AITL and PTCL with a T-follicle helper type (TFH).
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Linfoma de Células T Periférico , Antineoplásicos/uso terapéutico , Brentuximab Vedotina , Análisis Mutacional de ADN , Diagnóstico Diferencial , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoconjugados/uso terapéutico , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/terapia , Mutación/genéticaRESUMEN
T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.
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Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/terapia , Médula Ósea/patología , Manejo de la Enfermedad , Regulación Leucémica de la Expresión Génica , Humanos , Inmunofenotipificación , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/patología , Mutación , Estadificación de Neoplasias , Linfocitos T/patologíaRESUMEN
Clinical trials in T-cell prolymphocytic leukemia (T-PLL) are scarce. Based on a precursor study testing fludarabine, mitoxantrone, and cyclophosphamide followed by alemtuzumab (FMC-A), we aimed to improve this regimen by upfront combining subcutaneous (s.c.) alemtuzumab with FMC for four cycles followed by an alemtuzumab-maintenance (FMCA + A). This prospective multicenter phase-II trial assessed response, survival, and toxicity of that regimen administered to pretreated (n = 4) and treatment-naïve (n = 12) T-PLL patients. The best overall response rate after FMCA was 68.8% (n = 11) including five CRs (31.3%) and six PRs (37.5%). Six patients entered the alemtuzumab-maintenance. Median overall and progression-free survival was 16.7 and 11.2 months, respectively. Hematologic toxicities were the most frequent grade 3/4 side effects. A reduced incidence of CMV-reactivations was attributed to the prophylactic administration of valganciclovir. Overall, FMCA + A did not improve the efficacy of the FMC-A-regimen or of single i.v. alemtuzumab. It suggests that a chemotherapy backbone prevents efficient alemtuzumab dosing and confirms that intravenous alemtuzumab is to be preferred over its s.c. route in T-PLL. ClinicalTrials.gov identifier: NCT01186640.
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Alemtuzumab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Prolinfocítica de Células T/tratamiento farmacológico , Adulto , Anciano , Alemtuzumab/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Incidencia , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/mortalidad , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
Chimeric antigen receptor (CAR) T cells are genetically engineered autologous cells that express an activating receptor targeted towards one or more tumoral antigens. After ex vivo production and re-infusion, they are able to proliferate in the host and to recognize and kill tumor cells. Together with checkpoint inhibition, this new therapy is already being celebrated as a major medical breakthrough in recent years, due to the substantial benefit observed in clinical trials with patients with chemotherapy-refractory Bcell malignancies. These results have led to the recent approval of two CAR Tcell products by the Food and Drug Administration (FDA) in the United States. The list of targetable antigens and possible indications is continuously being expanded, as are the modifications to the CAR structure and the final cell products currently under investigation. In some patients, CAR Tcell therapy may lead to substantial toxicity including the cytokine release syndrome (CRS). In summary, CAR Tcell therapy has already provided clinical benefit to patients with Bcell malignancies unresponsive to conventional treatment. Yet, the therapy is still in an early stage of development, and the many opportunities for improvement in its various aspects as well as its future role in relation to conventional therapy will set the pace in the field of hematology for the next years or even decades.
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BACKGROUND: Extracorporeal photopheresis (ECP) has demonstrated efficacy as second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD). The aim of our study was to analyze whether the amount of ECP-treated cells in patients with SR, aGVHD has an impact on response at 1 month. STUDY DESIGN AND METHODS: Data on white blood cells, lymphocytes, monocytes, mononuclear cells, and neutrophils, including absolute counts and counts per kilogram of body weight in ECP products from patients with aGVHD, were collected. For each cell population, the median dose per single ECP and the cumulative doses collected during the first week and the first month of treatment were compared with the response to ECP. RESULTS: In total, 99 patients underwent 1215 ECP procedures. Overall response was defined as a complete response if all signs of aGVHD resolved or a partial response if greater than 50% resolution was reached without other, additional immunosuppression. An overall response was obtained by 75% of patients, including 53% complete responses. Univariate analysis showed a correlation of lymphocytes and mononuclear cells/kg body weight for a single procedure and overall response. In logistic regression analysis, no tested variable had an influence on response. In receiver operating characteristic curve analysis, cutoffs of 8.4 × 106 /kg body weight lymphocytes and 13.9 × 106 /kg body weight mononuclear cells were associated with an overall response to ECP at 1 month with 75% sensitivity. CONCLUSION: Our results in patients with steroid-refractory aGVHD confirm that response rates to ECP are high and that certain cutoff values for lymphocytes and mononuclear cells/kg body weight in each individual procedure can predict an overall response to ECP at 1 month.
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Recuento de Células Sanguíneas , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Fotoféresis , Enfermedad Aguda , Adulto , Capa Leucocitaria de la Sangre/citología , Peso Corporal , Femenino , Enfermedad Injerto contra Huésped/sangre , Humanos , Leucemia/mortalidad , Leucemia/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Curva ROC , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto JovenRESUMEN
Torquetenovirus (TTV) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. This study aimed to define TTV plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (HSCT). This was a single-center prospective longitudinal study involving 50 consecutive patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA levels were measured with quantitative PCR at 12 consecutive time points during the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV viremia during the follow-up period. Plasma viral loads evolved dynamically over time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL) occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau toward the end of the follow-up period. The type of malignancy, the use of antithymocyte globulin during conditioning, and the occurrence of acute graft-versus-host disease requiring systemic therapy had temporary effects on TTV dynamics. TTV levels showed a significant correlation with absolute lymphocyte counts following engraftment (rs = -.27; P < .01) and with cytomegalovirus (CMV; rs=.39; P < .01) and Epstein-Barr virus (EBV; rs=.45; P = .02) viral loads during phases of viremia. Immune-related clinical events were not predicted by TTV levels. TTV viremia occurred universally and was sustained throughout the first year after HSCT. Several variables and events before and after HSCT were correlated with TTV levels and hint toward immune marker properties of TTV, but their complex interactions might perturb the capability of TTV to predict immune-related complications in this population.
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Biomarcadores/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Torque teno virus/fisiología , Adulto , Biomarcadores/sangre , Citomegalovirus , Infecciones por Virus ADN/sangre , Infecciones por Virus ADN/inmunología , ADN Viral/sangre , Femenino , Herpesvirus Humano 4 , Humanos , Estudios Longitudinales , Recuento de Linfocitos , Masculino , Estudios Prospectivos , Trasplante Homólogo/efectos adversos , Carga ViralRESUMEN
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia 1 (MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL.
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Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Leucemia Prolinfocítica de Células T/tratamiento farmacológico , Terapia Molecular Dirigida , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Sulfonamidas/uso terapéutico , Adulto , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Resistencia a Antineoplásicos , Femenino , Ensayos Analíticos de Alto Rendimiento , Humanos , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/metabolismo , Masculino , Persona de Mediana Edad , Recurrencia , Sulfonamidas/farmacología , Resultado del TratamientoRESUMEN
Obesity is a well-known risk factor for the development of cancer, but its influence on the course of disease is still controversial. We investigated the influence of body mass index (BMI) on overall survival (OS) in 502 patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma in a subgroup analysis of the StiL (Study Group Indolent Lymphomas) NHL1 trial. We defined a cut-off of 22.55 kg/m2 by ROC calculation and Youden Index analysis and stratified patients into "low BMI" and "high BMI". Five-year OS was significantly longer in the high BMI group (82.2%) when compared to that of the low BMI group (66.2%) (HR 0.597; 95%CI 0.370-0.963; p = 0.034). BMI was also an independent prognostic factor for OS in multivariate analysis (HR 0.541; 95%CI 0.332-0.883; p = 0.014). Of note, patients had a significantly lower BMI in the presence than patients in the absence of B-symptoms (p = 0.025). BMI significantly impacts on OS in indolent non-Hodgkin's lymphoma and mantle cell lymphoma, which may be influenced by the effect of B-symptoms on BMI.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Índice de Masa Corporal , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Modelos de Riesgos ProporcionalesRESUMEN
The chemoimmunotherapy FCR (fludarabine and cyclophosphamide with rituximab) is the standard first-line treatment for physically fit chronic lymphocytic leukemia (CLL) patients. To assess the risks and benefits, we investigated health-related quality of life (HRQOL). 817 untreated CLL patients received either FC or FCR within the GCLLSG CLL8 trial. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire C30 was sent to all patients at baseline, after 3, 6, and 12 months and then yearly as follow-up. A total of 769 (94%) of 817 patients completed at least one questionnaire. Comparing HRQOL of CLL patients with the general German population, CLL patients' health declined in most scales except for global health and pain. No major differences in HRQOL were found during treatment or follow-up between both treatment arms. Females were more likely to have treatment-related symptoms than males. Although FCR was associated with more side effects, this did not influence HRQOL. During follow-up after FCR only minor improvement of HRQOL compared with FC was assessed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Casos y Controles , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Rituximab/administración & dosificación , Factores Sexuales , Encuestas y Cuestionarios , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease. Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.