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INTRODUCTION: Standard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors. PATIENTS AND METHODS: All consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Among 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively]. CONCLUSION: In patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.
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Neoplasias del Sistema Nervioso Central , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Masculino , Humanos , Persona de Mediana Edad , Trasplante Autólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre , Estudios Retrospectivos , Sistema Nervioso Central/patologíaRESUMEN
Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey. Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated. Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5). Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.
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Linfoma de Células B Grandes Difuso , Adulto , Humanos , Femenino , Adulto Joven , Persona de Mediana Edad , Masculino , Rituximab , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Estudios Retrospectivos , Prednisona/uso terapéutico , Vincristina , Turquía/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Etopósido , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéuticoRESUMEN
The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferonγ, and IL-6 regulator suppressor of cytokine signaling (SOCS)1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1 expression in effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression. SOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing-MM cells than unmodified MM cells. These data therefore demonstrate that modulation of SOCS1 may enhance immune response and efficacy of IMiDs in MM.
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Antineoplásicos/inmunología , Células de la Médula Ósea/efectos de los fármacos , Factores Inmunológicos/inmunología , Mieloma Múltiple/inmunología , Linfocitos T/efectos de los fármacos , Talidomida/análogos & derivados , Células de la Médula Ósea/inmunología , Línea Celular Tumoral , Citocinas/inmunología , Epigénesis Genética , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Lenalidomida , Mieloma Múltiple/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Células del Estroma/inmunología , Proteína 1 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Linfocitos T/inmunología , Talidomida/inmunologíaRESUMEN
BACKGROUND: Second line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. PATIENTS AND METHODS: Forty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. RESULTS: Thirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. CONCLUSION: Our results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Dexametasona/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pacientes Ambulatorios , Estudios Retrospectivos , Terapia Recuperativa/métodos , Trasplante de Células Madre , Trasplante Autólogo , GemcitabinaRESUMEN
CS1 is highly expressed on tumor cells from the majority of multiple myeloma (MM) patients regardless of cytogenetic abnormalities or response to current treatments. Furthermore, CS1 is detected in MM patient sera and correlates with active disease. However, its contribution to MM pathophysiology is undefined. We here show that CS1 knockdown using lentiviral short-interfering RNA decreased phosphorylation of ERK1/2, AKT, and STAT3, suggesting that CS1 induces central growth and survival signaling pathways in MM cells. Serum deprivation markedly blocked survival at earlier time points in CS1 knockdown compared with control MM cells, associated with earlier activation of caspases, poly(ADP-ribose) polymerase, and proapoptotic proteins BNIP3 and BIK. CS1 knockdown further delayed development of MM tumor and prolonged survival in mice. Conversely, CS1 overexpression promoted myeloma cell growth and survival by significantly increasing myeloma adhesion to bone marrow stromal cells (BMSCs) and enhancing myeloma colony formation in semisolid culture. Moreover, CS1 increased c-maf-targeted cyclin D2-dependent proliferation, -integrin beta7/alphaE-mediated myeloma adhesion to BMSCs, and -vascular endothelial growth factor-induced bone marrow angiogenesis in vivo. These studies provide direct evidence of the role of CS1 in myeloma pathogenesis, define molecular mechanisms regulating its effects, and further support novel therapies targeting CS1 in MM.
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Antígenos de Superficie/metabolismo , Médula Ósea/metabolismo , Adhesión Celular/fisiología , Proliferación Celular , Mieloma Múltiple/patología , Proteínas Proto-Oncogénicas c-maf/metabolismo , Células del Estroma/metabolismo , Animales , Antígenos de Superficie/química , Antígenos de Superficie/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Médula Ósea/patología , Membrana Celular , Supervivencia Celular , Ensayo de Unidades Formadoras de Colonias , Medio de Cultivo Libre de Suero/farmacología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Perfilación de la Expresión Génica , Humanos , Immunoblotting , Lentivirus/genética , Proteínas de la Membrana , Ratones , Ratones SCID , Proteínas de Microfilamentos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mieloma Múltiple/metabolismo , Mieloma Múltiple/prevención & control , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-maf/genética , ARN Interferente Pequeño/farmacología , Factor de Transcripción STAT3/metabolismo , Células del Estroma/patología , Activación Transcripcional , Transfección , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: We aimed to evaluate the clinical features of sclerodermatous chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (AHSCT). METHODS: We retrospectively analyzed 423 patients who underwent AHSCT. We assessed age, sex, pre-transplant diagnosis, conditioning regimen, GVHD prophylaxis, and occurrence of acute GVHD (aGVHD), chronic lichenoid and chronic systemic GVHD, and clinical properties of sclerodermatous GVHD. RESULTS: Sclerotic skin lesions developed in 22 patients after a mean of 752±647 days (median 480). aGVHD appeared in 17 patients, with hepatic involvement in 2, gastrointestinal tract involvement in 2 and skin involvement in 13 of these patients. Extensive chronic GVHD (liver, pulmonary, skin and oral mucosa) developed in 12 patients. Sclerosis was generalized in 19 patients (86.4%) and localized in 3 patients (13.6%). Leopard skin eruption appeared in 8 (36.4%) of the 19 patients with generalized sclerodermatous changes. In most cases, sclerotic lesions appeared on the trunk, and distal parts of the extremities were spared. Eight patients (36.4%) progressed from lichenoid to sclerodermatous lesions, 2 (9.1%) with lichenoid and sclerodermatous phases together and 12 (55.5%) with de novo sclerodermatous lesions. Five patients died because of late transplant-related complications. CONCLUSION: Sclerodermatous GVHD has a late onset and may be quite disabling. Unlike scleroderma, acral involvement is seen rarely. Although most lesions do not disappear in the course of the disease, most patients have a good prognosis.
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OBJECTIVE: We retrospectively analyzed the impact of pre- and post-transplant variables on the outcome of transplanta¬tion in 145 consecutive patients with acute myeloblastic leukemia (AML) allografted from their HLA-identical siblings in our single center cohort. RESULTS: The stem cell source used was bone marrow (BM) (36.6%) or peripheral blood (PB) (63.4%). Both neutrophil and platelet engraftments were observed on the median 14th day. Engraftment was faster in the PB group than in the BM group (p<0.0001). Severe acute graft versus host disease (aGvHD) was observed in 27.9% of the patients while chronic (c)GvHD developed in 61.2%. The use of PB was associated with more severe aGvHD. Estimated leukemia-free survival (LFS) and overall survival (OS) at 10 years were 43.4%±5.2% and 52.7%±4.6%, respectively. CONCLUSION: Both in univariate and multivariate analyses for LFS and OS, remission status at transplant and the presence of aGvHD were independent risk factors.
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Graft versus host disease (GvHD) is the most prominent cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (Allo-HCT). Extracorporeal photoimmunotherapy (ECP) is an alternative therapeutic modality in steroid and/or cyclosporin-A refractory GvHD developing after Allo-HCT. The aim of this study was to evaluate whether there was any relation between serum TNF-a levels and the response to ECP in patients with steroid refractory of extensive chronic GvHD. Between March 2001 and August 2003, seven patients (male: 1, female: 6) had ECP for treatment of steroid refractory extensive chronic GvHD. Five age and gender matched healthy volunteers were included in this study as the control group. The age of the patients ranged from 18 to 49 years. All patients were allografted from HLA-identical sibling donors. The median number of ECP sessions was 10 (8-36), consisting of two sequential cycles monthly. For measurement of serum TNF-a levels, blood samples were obtained both prior to ECP (basal) and after the first and second in all patients and in five patients after the 10th session. Serum TNF-a levels (Quantakine HS, R&D system, UK) were measured in peripheral venous blood samples by an ELISA method. ECP was given at a median of 5.8 months (1-14 months) after allo-HCT. No complications were seen during or after the ECP procedures. The median time of an ECP session was 183 minutes. The median volume of Uvadex used per session was 4.40 ml (3.61-5.61). The basal mean level of TNF-a was higher in patients than in the control group (2.47+/-0.83 pg/ml vs. 1.75+/-0.06, p=0.05). The mean TNF-a levels decreased from 2.47+/-0.83 pg/ml to 1.77+/-0.93 pg/ml after the initial session (p=0.045) and from 2.32+/-0.92 pg/ml to 1.69+/-0.93 pg/ml after the second day (p=0.015). After completion of the ECP sessions, extensive chronic GvHD recovered in only three patients. In three clinically responsive patients, the TNF-a levels were significantly reduced after both the second and tenth sessions. In contrast, in two patients not responding to ECP therapy, TNF-a levels were increased. In order to report whether these changes in TNF levels is an early predictor for evaluation of the efficacy of ECP in extensive chronic GvHD, TNF-a levels should be studied in a larger series.
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Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia , Fototerapia , Factor de Necrosis Tumoral alfa/sangre , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trasplante HomólogoRESUMEN
UNLABELLED: Depletion of bone marrow (BM) from erythrocytes is used to prevent early hemolysis in major ABO incompatible allogeneic hematopoietic cell transplantation (Allo-HCT). This method was also strongly recommended before storing of autologous and even allo-BM for volume reduction in order to prevent early hemolysis and DMSO toxicity after infusion. In our center, erythrocyte depletion of BM harvests has been performed on a continuous flow cell separator, which used a closed system with a high mononuclear cell (MNC) yield and low rate of erythrocyte contamination. According to the protocol of a cellular therapy approach in a cardiovascular collaborative study we have to adopt the process to lower volumes. We aimed to compare our results with standard volume (SV) (historical control) to low volume ED procedures. PATIENTS AND METHOD: Data has been collected from the last five years. We analyzed 28 cases in the SV group (BM volume >750ml) and 39 cases in the low volume (LV) group. Nineteen of these cases were allogeneic, and 48 were autologous procedures. We used the software COBE PBSC coll vers 5.1 and a standard disposable set (Gambro BCT, Lakewood, USA) for the procedure, and simultaneously, a double bag system with intermediate connectors were used to overcome re-circulation (COBE Spectra Bone Marrow Processing Set, Lakewood USA). RESULTS: The mean volume reduction was 88% (range, 84.4-93.5%) for SV and 90.8% (range, 87.2-91.3%) for the LV group. We did not find any significant difference for MNC yield, volume reduction rate and CD34+ cell recovery between the SV and LV group. There were no complications experienced with regards to device or technical difficulties during procedures. Acute massive intravascular hemolysis was not observed in allogeneic recipients. CONCLUSION: ED and volume reduction with COBE spectra produced successful results in standard and low harvest volumes. This process can be successfully applied to lower volumes and comparable results to the SV harvest can be achieved for the ED rate, reduction of volume and recovery of MNCs and CD34+ cells.
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Médula Ósea , Separación Celular/métodos , Eritrocitos , Trasplante de Células Madre Hematopoyéticas/métodos , Antígenos CD34 , Células Madre Hematopoyéticas , Hemólisis , Humanos , Leucocitos Mononucleares , Estudios Retrospectivos , Programas Informáticos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Transplant physicians are generally using the recipient's actual body weight (ABW) for the calculation of the content of CD34+ cells in the harvest material in hematopoietic stem cell transplantation (HSCT). As a reference center performing both the stem cell collection and HSCTs, we aimed to evaluate whether there were any differences for neutrophil recovery by calculating the CD34+ cell content in the graft according to actual, ideal (IBW) or adjusted IBW (AIBW) of the recipients in both autologous (n=148) and allogeneic stem cell collection setting (n=234). We observed a negative correlation between the neutrophil recovery and the cell doses infused as to each of these BWs in the allo-HSCT group, but not in the auto-HSCT group. This negative correlation was stronger for IBW and AIBW rather than for ABW in allo-HSCT group. In addition, calculations for both IBW and AIBW in autologous and allogeneic transplants revealed a significant difference in comparison to ABW for different cut-off values of infused CD34+ cells. Consequently, we suggested that both IBW and AIBW based calculations of CD34+ cells infused are better predictors of neutrophil recovery in comparison to ABW in allo-HSCT. We were not able to show this impact in autologous transplants.
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Antígenos CD34 , Peso Corporal , Recuento de Células/métodos , Trasplante de Células Madre Hematopoyéticas/normas , Células Madre Hematopoyéticas/citología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Trasplante Autólogo , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND/AIMS: Acute graft-versus-host disease (GVHD) is a common complication of haematopoietic cell transplantation (HCT), with the gastrointestinal tract (GIT) as one of the main target organs. There is a lack of consensus regarding the site in GIT with the highest sensitivity for biopsy. The present study aimed to determine the endoscopic and histological findings in acute GVHD. MATERIALS AND METHODS: The data of 111 patients who had received allogeneic HCT were retrospectively reviewed. RESULTS: Allogeneic HCT was performed in 111 patients, of whom 27 (24.3%) had developed acute GVHD. Nineteen of the 111 patients with intestinal symptoms were evaluated for intestinal involvement, and 17 were diagnosed with acute intestinal GVHD. Upper endoscopic findings had a sensitivity of 64.7%, a specificity of 50%, a positive predictive value of 91.6% and a negative predictive value of 14.2%. The diagnostic accuracy of upper endoscopy was 63.1%. Lower endoscopic findings had a sensitivity of 40% and a specificity of 0%. The diagnostic accuracy of upper endoscopy with duodenal biopsy and sigmoidoscopy was 94.1%. CONCLUSION: Endoscopic findings are nonspecific in acute intestinal GVHD. There is little agreement between endoscopic findings and histopathology; thus, biopsies are essential. In patients with intestinal symptoms after HCT, upper endoscopy with duodenal biopsy and sigmoidoscopy has an acceptable diagnostic yield for intestinal involvement.
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Endoscopía Gastrointestinal/estadística & datos numéricos , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Intestinales/diagnóstico , Adulto , Biopsia/métodos , Duodeno/patología , Endoscopía Gastrointestinal/métodos , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Enfermedades Intestinales/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Trasplante HomólogoRESUMEN
BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.
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Conductos Biliares/metabolismo , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas , Hepatopatías/metabolismo , Péptidos/metabolismo , Adolescente , Adulto , Enfermedades de los Conductos Biliares/complicaciones , Enfermedades de los Conductos Biliares/metabolismo , Conductos Biliares/química , Conductos Biliares/patología , Enfermedad Crónica , Epitelio/metabolismo , Epitelio/patología , Femenino , Humanos , Inmunoquímica , Hígado/química , Hígado/patología , Hepatopatías/complicaciones , Masculino , Persona de Mediana Edad , Péptidos/análisis , Péptidos/genética , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Trasplante Homólogo , Factor Trefoil-3RESUMEN
We investigated the peripheral blood gene expression profile of interferon induced transmembrane protein 1 (IFITM1) in sixty chronic myeloid leukemia (CML) patients classified according to new prognostic score (NPS). IFITM1 is a component of a multimeric complex involved in the trunsduction of antiproliferative and cell adhesion signals. Expression level of IFITM1 was found significantly different between the high- and low-risk groups (P = 9.7976 x 10(-11)) by real-time reverse transcription polymerase chain reaction (RT-PCR). Higher IFITM1 expression correlated with improved survival (P = 0.01). These results indicate that IFITM1 expression profiling could be used for molecular classification of CML, which may also predict survival.
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Biomarcadores de Tumor/análisis , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Proteínas de la Membrana/biosíntesis , Adulto , Anciano , Antígenos de Diferenciación , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/clasificación , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de SupervivenciaRESUMEN
ABO incompatibility is not a contraindication for allogeneic bone marrow transplantation, but this procedure requires an extra effort for erythrocyte or plasma depletion in certain well established conditions. Some acute or delayed immunohematological complications such as acute or chronic hemolysis and pure red cell aplasia may be encountered. In this study the outcome and transplant related complications of ABO incompatible and identical cases, who have received allogeneic peripheral blood stem cells from their HLA identical siblings were compared with each other. Ninety-one patients (CML 36, AML 37, other 18) were analyzed retrospectively including 51 (60.4%) ABO identical patients and 36 (39.6%) ABO mismatched (MM) patients, who have a bi-directional MM (n= 5), major MM (n= 16), minor MM (n= 9) and Rh MM (n= 6). Median follow up was 13 (0.5-43.0) months. We did not observed any significant differences between two groups (identical vs non-identical) in terms of acute hemolysis preceding stem cell infusion, peritransplant transfusion demand, acute- and chronic graft versus host disease. There was no change in estimated disease free survival and overall survival durations. We did not observed any influence of ABO/Rh incompatibility on short term outcome in allogeneic peripheral blood stem cell transplantation in our series and did not recommend further manipulation of the infused stem cells.
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This prospective multicenter phase III clinical trial was designed to assess efficacy and safety of G-CSF as an adjunct to de novo AML remission induction therapy (www.clinicaltrials.gov. NCT00820976). Patients' characteristics were similar in both arms. G-CSF improved severity and duration of leukopenia. Three-year OS were similar (25.6 ± 5.1% vs. 31.8 ± 5.6%) in both arms except for patients with myeloblastic features. Significant factors for better survival were the use of G-CSF (p=0.049), female sex (p=0.05) and single induction cycle (p<0.001) in multivariate analysis. Female patients performed better than male patients. Better survival obtained among female AML patients needs to be validated within the context of cytogenetic analysis.
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Resistencia a Antineoplásicos/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neutropenia/tratamiento farmacológico , Inducción de Remisión , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Therapy in refractory chronic idiopathic thrombocytopenic purpura is usually a difficult and expensive procedure, with little benefit to the patient, and the results are typically only short-term improvements. In this case report, we study a patient with refractory chronic idiopathic thrombocytopenic purpura who was initially treated with a first line therapy with only partial and temporary benefit, and in whom none of the experimental therapies tried later on resulted in any long lasting effect. In the case study conducted, among all the second-line experimental treatment modalities, only the proposed new protocol (the Modified Malmö Protocol) resulted in a major response. Our results suggest that, the Modified Malmö Protocol may be a promising second-line treatment option for severely refractory idiopathic thrombocytopenic purpura cases.
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Ciclofosfamida/administración & dosificación , Factor IX/administración & dosificación , Factor VIII/administración & dosificación , Factor VII/administración & dosificación , Inmunoglobulina G/administración & dosificación , Púrpura Trombocitopénica Idiopática/terapia , Adulto , Combinación de Medicamentos , Humanos , MasculinoRESUMEN
BACKGROUND: Therapeutic plasma exchange (TPE) seems to be an effective approach for clearing toxins, immune-mediated antigens, and other particles from the circulation. The aim of this study was to analyze the positive effects of TPE on clinical and biochemical parameters of liver failure. PATIENTS AND METHODS: Between January 2001 and March 31, 2005 individuals (men/women, 17/14; median age, 42.7+/-15.8 y) with acute and chronic liver failure who underwent a total of 113 TPEs (median session 3.7) were retrospectively reviewed. TPE was performed using the Fresenius AS-TEC 204 cell separator (Fresenius AG, Germany). The indication for TPE was severe coagulopathy (prothrombin time >20 s), severe hepatic encephalopathy, hyperbilirubinemia, and candidacy for liver transplantation. All patients were examined before and immediately after the last TPE session. RESULTS: When compared with baseline, there was significant improvement in hepatic encephalopathy stage (from median score 3.0 to 1.0, P=0.001), serum prothrombin time (from median 26.0 to 20.0 s, P=0.003), aminotransferases (P<0.001), and total bilirubin levels (from median 35.0 to 23.3 mg/dL, P<0.001) after TPE. Thirteen of the thirty-one individuals (41.9%) died in the hospital. The mean follow-up period of 18 survival patients was 35.9+/-5.6 months and 10 of those survived (55.6%, 10/18). No serious adverse effect of TPE was observed in any of the patients during or after completion of TPE. Only 6 patients experienced minor transfusion reactions. CONCLUSIONS: TPE seems to be effective in improving hepatic encephalopathy stage and liver tests in individuals with acute and chronic liver failure. The data suggest that TPE is safe and tolerable in such individuals, however, overall survival remains poor despite TPE.
Asunto(s)
Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Fallo Hepático/terapia , Intercambio Plasmático/métodos , Albúmina Sérica/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Fallo Hepático/sangre , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
OBJECTIVES: Data regarding the long-term treatment of ursodeoxycholic acid (UDCA) in individuals of chronic graft-vs.-host disease (cGVHD) of the liver are limited. The aims of this prospective study were to determine whether, (i) UDCA treatment is useful as a long-term treatment for individuals with limited cGVHD of the liver following allogeneic hematopoietic cell transplantation, and (ii) the tolerability of UDCA treatment in such individuals. METHODS: Fifteen consecutive patients with de novo isolated cGVHD of the liver were included. All individuals were treated with UDCA at a dose of 13 mg/kg/d for 1 yr. Clinical evaluation and laboratory testing were assessed at 30-d intervals during UDCA therapy and every 30 d after discontinuation of UDCA for a total of 3 months. RESULTS: At the end of the treatment, 60% of patients with cGVHD of the liver had normal liver tests, the remaining 40% of patients demonstrated improvement in their abnormal liver tests (partial responders), whereas none of the patients had worsening of the liver tests. When compared with baseline, there was a significant decrease in the serum aminotransferases, alkaline phosphatase and gamma-glutamyl transpeptidase levels after completion of the UDCA treatment at 12 months (p < 0.01). No significant increase in serum liver enzyme tests was observed at the third month after the completion of therapy. Pruritus in seven of nine patients resolved after UDCA treatment. All patients completed their assigned treatment with no major adverse event. CONCLUSION: Long-term UDCA therapy appears to be effective, safe and tolerable in individuals with cGVHD presenting with isolated liver involvement.