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1.
Clin Transplant ; 32(9): e13359, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30053318

RESUMO

BACKGROUND: Recent reports have showed that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are predictors of progression-free survival (PFS) and overall survival (OS) in many types of cancer. This study evaluates the predictive value of NLR, MLR, and PLR for survival in MM patients treated with to ASCT. METHODS: A set of data consisting of 150 patients who underwent autologous stem cell transplantation (ASCT) for MM was collected retrospectively. The prognostic value of NLR, MLR, and PLR was investigated with Kaplan-Meier method. RESULTS: The prognostic value of NLR, MLR, and PLR was analyzed by a receiver operating characteristic (ROC) curve established to determine the cutoff. These cutoff values of NLR, PLR, and MLR were found 1.46, 86, and 0.27, respectively, on the 100th day of post-transplantation period. The overall survival (OS) and the post-transplantation OS of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation were shorter than the other group (P = 0.05, P = 0.018 [NLR], P = 0.05, P = 0.002 [MLR], P = 0.000, P = 0.001 [PLR]). The post-transplantation progression-free survival (PFS) of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation was shorter as well (P = 0.036, P = 0.001, P = 0.001, respectively). CONCLUSION: As increased NLR, MLR, and PLR predicted poor clinical outcome in MM patients with autologous transplantation in this study, they may serve as cost-effective and rapidly available prognostic biomarkers for these patients.


Assuntos
Biomarcadores Tumorais/sangue , Plaquetas/patologia , Linfócitos/patologia , Monócitos/patologia , Mieloma Múltiplo/patologia , Neutrófilos/patologia , Adulto , Idoso , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
2.
Chemotherapy ; 60(4): 219-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25871894

RESUMO

Multiple induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). However, there have been no prospective randomized trials that directly compare these regimens. In this study, we wanted to evaluate the outcome of 50 adult ALL patients treated with BFM (i.e. Berlin-Frankfurt-Munster, n = 20) and hyper-CVAD (n = 30) protocols between March 2006 and October 2012. The median age was 25 years in the BFM group and 30.5 years in the hyper-CVAD group with a male/female ratio of 15:5 and 17:13, respectively. Forty-five percent of the patients in the BFM group and 30.3% in the hyper-CVAD group were <25 years old. The majority of cases were B cell in origin (80% in the BFM group and 70% in the hyper-CVAD group). Complete remission after induction therapy was achieved in 95 and 96% of the patients, respectively. The median follow-up time was 37 months. The 5-year survival rate was higher in the BFM group than in the hyper-CVAD group (59 vs. 34%). There were also no complications which could cause a delay during the hyper-CVAD regimen. Both chemotherapies were well tolerated. None of the patients died from drug-related toxicity. Only mild liver enzyme elevations were seen as toxicity in the BFM group; these did not cause any delay in therapy. The BFM regimen seems to be feasible for adult patients with ALL in terms of tolerability and efficacy, especially in young adults.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Asparaginase/administração & dosagem , Ciclofosfamida/administração & dosagem , Daunorrubicina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
3.
Turk J Haematol ; 36(2): 81-87, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30724061

RESUMO

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
4.
J Lab Physicians ; 10(4): 363-369, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498304

RESUMO

BACKGROUND: Recent reports showed neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. MATERIALS AND METHODS: We retrospectively examined the PLR, NLR, and MLR in a cohort of 186 newly diagnosed multiple myeloma (MM) patients. This study investigated the prognostic relevance of NLR, PLR, and MLR in MM patients. NLR, PLR, and MLR were calculated from whole blood counts before therapy. The Kaplan-Meier curves and multivariate Cox models were used for the evaluation of survival. RESULTS: Applying cutoff of 1.9 (NLR), 120.00 (PLR), and 0.27 (MLR), decreased PLR showed a negative impact on the outcome. Decreased PLR is an independent predictor for PFS and OS. There were no significant differences in median survival between the high and low NLR (P = 0.80) and MLR (P = 0.87) groups. CONCLUSIONS: In this study, thrombocytopenia and low PLR are associated with poor survival in MM patients does this P value apply to thrombocytopenia or low PLR and may serve as the cost-effective prognostic biomarker.

5.
Indian J Hematol Blood Transfus ; 34(4): 677-683, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30369740

RESUMO

Peripheral blood is the prefered source for hematopoietic stem cells for hematopoietic stem cell transplantation. The efficiency of peripheral blood stem cell (PBSC) collection can vary among devices. In this study we aimed to compare feasibility and effectivity of apheresis procedures of the different systems. Two apheresis systems [Com.Tec (Fresenius Healthcare) and Spectra Optia (Caridian BCT)] were used in our center for the collection of PBSCs for autologous and allogeneic transplantation. We retrospectively analysed 190 apheresis procedures performed in healthy donors and patients between June 2012 and November 2014 in Department of Hematology, Dokuz Eylul University. PBSCS were collected by Fresenius cell separator (64 procedure) or Spectra Optia cell separator (126 procedure). Mobilization treatments were G-CSF (26.8%), cyclophosphamide plus G-CSF (48.4%), prelixafor plus G-CSF (14.7%), ESHAP (10%) and others. Patient and donor characteristics (age, weight, volume processed, disease, mobilization regimes) were similar in Fresenius and Spectra Optia apheresis groups. Altough both collected PBSCs efficiently, the amount of CD34+ cell in product collected by Spectra Optia device was significantly higher (p < 0.05) and product volume was lower than Fresenius Com.Tec significantly (p < 0.05). "CD34+ collection efficiency" with Spectra Optia was significantly higher than Fresenius Com.Tec (CE2: 87%, 70%, p = 0.033) regarding all procedures. High collection efficiency and low product volume may be a significant characteristic of Spectra Optia device (mean 187 mL, product CD34+ cell: 1576 µL).

6.
Turk J Haematol ; 35(4): 271-276, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29923493

RESUMO

Objective: High-doses of melphalan treatment with autologous stem cell transplantation in multiple myeloma (MM) remains a major treatment modality in suitable patients. A minimal dose of 2x106/kg CD34+ cells is preferred to achieve engraftment. Some patients need multiple leukapheresis procedures to achieve the necessary number of CD34+ cells, but this can cause a high volume of stem cell product that cannot be given in a single day. Whether or not the number of infusion days affects engraftment has not been studied before. We aimed to evaluate the impact of reinfusion of stem cells on multiple days on engraftment results. Materials and Methods: Demographic features, CD34+ cell doses, neutrophil and platelet engraftment days, hospitalization days, and number of infusion days of 149 autologous transplantations of 143 MM patients were evaluated retrospectively. Results: The data of 143 MM patients who were transplanted were analyzed retrospectively. Median age was 55±8.5 (range: 26-70) years with a male/female ratio of 91/58. Hospitalization days for all patients were 24±6 (range: 14-50) days. Mean CD34+ cell number was (7.5±5.3)x106/kg (range: 1.5-31x106/kg). CD34+ cells were reinfused in 1 day in 80.5% (n=120) of the patients, 2 days in 18.2% of the patients (n=27), and 3 days in 1.3% of the patients (n=2). For 29 patients, reinfusion was applied in more than 1 day because of the high volume of stem cell product. We did not see any dimethyl sulfoxide toxicity, cardiac arrhythmia, or volume overload complications. Hypertensive attacks during infusion were easily controlled by furosemide treatment. In the group with multiple infusions, the infused CD34+ cell numbers had a mean of (4.8±2.8)x106/kg, and in the single infusion group the mean was (8.1±5.5)x106/kg. There were no statistical differences between the two groups regarding platelet and neutrophil engraftment days (p=0.850, r=0.820 and p=0.500, r=0.440). There was no statistical difference between the two groups for hospitalization days (p=0.060, r=0.050). Conclusion: In cases with a high volume of stem cell product to acquire adequate stem cells, reinfusion can be safely applied across multiple days without any delay in engraftment.


Assuntos
Antígenos CD34/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante , Transplante Autólogo
7.
Hematology ; 23(10): 771-777, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29996726

RESUMO

OBJECTIVES: This report presents final results (24 months of follow-up) from the first prospective, national study of frontline nilotinib in chronic myeloid leukemia (CML) patients in Turkey. METHODS: Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N = 112) received nilotinib 300 mg twice daily. The primary endpoint, which was the cumulative rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months, was previously reported (66.1% [80% CI, 59.7%-72.0%]). ClinicalTrials.gov identifier NCT01274351 Results: By 24 months, 83.0% of patients achieved MMR, and 50.9% achieved MR4.5 (BCR-ABL1IS ≤0.0032%). Safety results at 24 months were consistent with those at 12 months. No additional deaths or disease progressions to accelerated phase/blast crisis were observed between 12 and 24 months. DISCUSSION: Treatment with nilotinib 300 mg twice daily for 2 years provided high MMR with a good safety/tolerability profile in newly diagnosed CML-CP patients in Turkey. Assessment of MMR across time points showed increasing rates through 18 months, after which as lower rate of increase was observed. The safety profile of nilotinib 300 mg twice daily with 24 months of follow-up was similar to that observed at 12 months, and no new safety concerns were identified. These efficacy and safety findings are consistent with the results from the 12-month analysis of this study and from previous nilotinib studies. These findings support nilotinib as an option for frontline treatment of CML-CP. CONCLUSION: Frontline nilotinib treatment provided sustained efficacy, with good tolerability, over 24 months in newly diagnosed CML-CP patients.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Pirimidinas/administração & dosagem , Adulto , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Turquia
8.
Hematology ; : 1-7, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486663

RESUMO

OBJECTIVES: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months. METHODS: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. This study is registered with ClinicalTrials.gov (NCT01274351). RESULTS: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1IS ≤0.0032%) by 12 months. During the first year of treatment, one patient progressed to blast crisis and two patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. CONCLUSION: These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP with low and intermediate risk.

9.
Leuk Lymphoma ; 48(7): 1372-8, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17613766

RESUMO

In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p < 0.0001). In WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin <10 g/dl, neutrophil count <0.5 x 10(9)/L, platelet count <50 x 10(9)/L had an unfavourable prognostic impact on survival in multi-variate analysis. Our conclusions support the previous findings on the value of WHO classification for prediction of prognosis in MDS.


Assuntos
Síndromes Mielodisplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica , Classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Turquia/epidemiologia , Organização Mundial da Saúde
10.
Clin Appl Thromb Hemost ; 13(2): 201-5, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17456631

RESUMO

Preeclampsia has been associated with increased platelet activation detected before disease onset. Platelets are involved in hemostasis and also directly initiate an inflammatory response of the vessel wall. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis, and also as a mediator of inflammation. Platelets may release inflammatory mediators such as soluble CD40 ligand. The plasma level of soluble CD40 ligand was investigated during preeclamptic (n =20) and normal pregnancies (n = 20) to emphasize inflammatory response in preeclampsia. The mean soluble CD40 ligand levels were 1.08 +/- 0.43 ng/mL in patients with preeclampsia and 0.76 +/- 0.24 ng/mL in healthy pregnant women, which was statistically significant (P = .01). To clarify whether inflammation may cause inappropriate endothelial cell activation or inappropriate endothelial cell activation may start this inflammatory response, future studies are needed in a larger study population.


Assuntos
Ligante de CD40/sangue , Pré-Eclâmpsia/sangue , Adulto , Feminino , Humanos , Gravidez , Solubilidade
11.
Turk J Haematol ; 24(1): 23-7, 2007 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-27263481

RESUMO

Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

12.
Clin Appl Thromb Hemost ; 12(1): 9-14, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16444429

RESUMO

An increased incidence of thromboembolic events has been described in women receiving systemic chemotherapy for breast cancer. The effect of anthracycline-based adjuvant chemotherapy regimens on fibrinolytic system markers of plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty-four patients with operable breast cancer (median age, 54.5 years; range, 37-72 years) enrolled in our study. Stage I-II and stage IIIA cases received EC (Epirubicin 90 mg/m(2)/d1, I.V. and cyclophosphamide 600 mg/m(2)/d1, I.V.) and FEC (5-fluorouracil 500 mg/m(2)/d1, I.V., epirubicin 100 mg/m(2)/d1, I.V., and cyclophosphamide 500 mg/m(2)/d1, I.V.) as an adjuvant chemotherapy regimen, respectively. Each group consisted of 12 patients. Blood samples were obtained at baseline and just before the third cycle of EC and fourth cycle of FEC chemotherapy regimens. Plasma TAFI antigen and PAI-1 levels did not disclose any statistical difference between basal and postchemotherapy levels within each group and between two groups. Although postchemotherapy D-dimer levels were statistically higher in the FEC group than in the EC group, results in both groups were within normal ranges. More studies concerning the role of fibrinolytic system in breast cancer patients receiving chemotherapy, probably including cases with advanced stage and with different chemotherapy regimens and dose intensities, are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carboxipeptidase B2/sangue , Epirubicina/administração & dosagem , Inibidor 1 de Ativador de Plasminogênio/sangue , Adulto , Idoso , Antraciclinas/uso terapêutico , Neoplasias da Mama/sangue , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Fibrinólise/efeitos dos fármacos , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade
13.
Ophthalmic Surg Lasers Imaging ; 37(3): 236-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16749262

RESUMO

A 35-year-old man with systemic non-Hodgkin's lymphoma and bilateral choroidal involvement is described. Indocyanine green angiography depicts choroidal involvement much better than fluorescein angiography and seems to be superior in diagnosing and monitoring patients with systemic non-Hodgkin's lymphoma and choroidal involvement.


Assuntos
Neoplasias da Coroide/diagnóstico , Corantes , Angiofluoresceinografia , Verde de Indocianina , Linfoma de Células B/diagnóstico , Linfoma de Células T/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Coroide/tratamento farmacológico , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Masculino
14.
Turk J Haematol ; 23(2): 119, 2006 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-27265295

RESUMO

t(1;3)(p36;p21) is a recurrent reciprocal translocation found in a subset of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and poor prognosis. In the literature, some authors have suggested that this recurrent translocation is closely associated with prior chemotherapy including alkylating agents in various hematologic malignancies. We identified a recurring translocation, t(1;3)(p36;p21), in our patient with MDS/AML(M2), although she had not been given any kind of treatment previously.

16.
Turk J Haematol ; 23(3): 136-41, 2006 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27265480

RESUMO

It has been shown that imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia, inhibits the effect of stem cell factor, which has a central role in erythropoiesis. In some polycythemia vera (PV) patients, it has inhibited autonomous erythroid colony growth in vitro and decreased the need for phlebotomy. In this study we have investigated the effect of insulin like growth factor (IGF)-I, stem cell factor (SCF) and erythropoietin (Epo) with interleukin (IL)-3, granulocyte macrophage-colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF) in the presence of imatinib mesylate on the erythroid progenitors derived from peripheral blood mononuclear cells of three patients with PV and four healthy controls in semisolid medium. Erythroid colony formation from hematopoietic progenitors obtained from healthy controls was observed only in the presence of all cytokines. However, the number of erythroid colonies could not reach that of patients with PV. Inhibition of imatinib mesylate on erythroid colony growth was evident. Hematopoietic progenitors of patients with PV displayed two types of colony formation: the first type was exogenous cytokine-independent and was hypersensitive to current cytokines, and the second displayed hypersensitivity to current exogenous cytokines, but was exogenous cytokine-dependent. For both types, the inhibitory effect of imatinib mesylate was striking in the presence of all cytokines including IL-3, GM-CSF and Epo. There is no direct evidence yet that imatinib mesylate could inhibit the effect of IL-3, G-CSF, GM-CSF, Epo and IGF-I on erythropoiesis. Considering former studies together with results of this study, it can be argued that imatinib mesylate is effective in PV on the intersecting signal transduction mechanisms in which stem cell factor and its receptor may have a part.

17.
Turk J Haematol ; 23(2): 94-9, 2006 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-27265290

RESUMO

BACKGROUND: The clinical course of patients with inflammatory bowel disease (IBD) is frequently complicated by thromboembolic events and may involve the arterial and venous systems. Although not uniformly documented, several studies document substantial alterations in markers of coagulation and fibrinolysis in patients with IBD. METHODS: 45 patients with IBD (31 UC,14 CD) were included in the study. Age and sex matched 16 volunteers were used as a control group. TAFI antigen was determined using an ELISA kit VisuLiseTM for quantitative measurement. RESULTS: Inflammatory parameters such as white blood cell, platelet levels, erythrocyte sedimentation rate, C-reactive protein were found to be significantly higher in active disease group compared to inactive patients. Coagulation parameters of prothrombin time, activated partial thromboplastin time and d-dimer levels showed no significant difference between active and inactive IBD. Fibrinogen levels were significantly higher in clinically active IBD patients. Plasma TAFI levels demonstrated no significant difference between active and control, inactive and control as well as active and inactive groups. We observed no significant changes in levels of ß-TG and PF-4 between active and inactive disease group. CONCLUSIONS: We studied plasma TAFI levels in IBD. In conclusion, plasma TAFI levels does not appear to represent to be a marker of activation in IBD in contrast to literature. So further studies covering more patients with different clinic and disease activity status might improve the perspective on this issue.

18.
Exp Hematol ; 44(4): 223-30, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26774384

RESUMO

Multiple myeloma (MM) is a hematologic cancer characterized by malignant proliferation of plasma cells and their precursors. Immunosuppressive CD4+CD25+Foxp3+ regulatory T (Treg) cells are increased in the peripheral blood of patients with MM. On the basis of this finding, we sought to evaluate the ex vivo effect of CD4+CD25+Foxp3+ Treg cells on the anti-tumor effect of the proteosome inhibitor bortezomib on MM cells. We collected peripheral blood and bone marrow aspiration samples from 20 patients with newly diagnosed MM and isolated CD4+CD25+Foxp3+ Treg cells from peripheral blood mononuclear cells. The bone marrow mononuclear cells were cultivated in RPMI at 37°C and 5% CO2 for 72 hours. The LD50 doses of bortezomib, isolated Treg cells, and their combination were added. After 24 hours, the viability of CD138+ myeloma cells was evaluated by WST-1. We compared the anti-tumor effect of bortezomib alone and in combination with Treg expansion and statistically analyzed the measured differences with respect to the clinical parameters of the patients. Treg cells had varied effects on bortezomib, increasing, decreasing, or not changing its anti-tumor effect. The increased in vitro anti-tumor effect of bortezomib after Treg cell expansion was correlated in patients who did not develop bortezomib resistance in vivo (p = 0.022). These patients with in vivo non-bortezomib-resistant MM also responded to Treg expansion with decreased cell viability (p = 0.024). Our data indicate that the ex vivo expansion of Treg cells increased the cytotoxic effect of bortezomib in clinically sensitive cases.


Assuntos
Antineoplásicos/farmacologia , Bortezomib/farmacologia , Mieloma Múltiplo/imunologia , Linfócitos T Reguladores/imunologia , Idoso , Idoso de 80 Anos ou mais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Superfície/metabolismo , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunofenotipagem , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Estadiamento de Neoplasias , Sindecana-1/metabolismo , Linfócitos T Reguladores/metabolismo
19.
Expert Opin Pharmacother ; 17(14): 1851-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27501474

RESUMO

OBJECTIVE: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1(IS)]) by 12 months. METHODS: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. RESULTS AND CONCLUSIONS: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR(4.5) (BCR-ABL1(IS) ≤ 0.0032%) by 12 months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
20.
Leuk Lymphoma ; 46(5): 753-6, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16019514

RESUMO

The anti-tumor effect of cyclo-oxygenase (COX) inhibitors has been documented in several studies. COX2 inhibitors have attracted more attention because of the fewer side-effects and the more prominent anti-tumor effects. However, experience with these drugs in hematological malignancies is limited. In our study, a potent COX2 inhibitor, nabumetone (NBT), was investigated for its anti-proliferative and apoptotic effects in K-562 and Meg-01 chronic myeloid leukemia blastic cell lines as a single agent or in combination with adriamycin (ADR) and interferon alpha (IFN-a). In these cell lines, a dose-dependent inhibition of proliferation was observed with NBT. We observed no significant apoptotic effect of NBT. However, NBT potentiated the apoptotic effect of ADR in the K-562 cell line. Bcl-2 expression was reduced by NBT (11% vs. 2%). The combination of NBT with IFN did not have any significant effect on the K-562 cell line. We suggest that NBT inhibits proliferation and potentiates the apoptotic effect of ADR in chronic myeloid leukemia cell lines.


Assuntos
Antineoplásicos/farmacologia , Butanonas/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Nabumetona , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese
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