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The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients' survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.
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Patients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS-CoV-2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS-CoV-2 less effective than in immunocompetent individuals. Molnupiravir is one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death in COVID-19 in the general population. In this context, 175 haematology patients with diagnosed COVID-19, and treated with MOL between January and April 2022, came under our scrutiny with a view to defining their clinical characteristics and outcomes. The most common underlying conditions were lymphomas (45%), multiple myelomas (21%) and acute leukaemias or myelodysplastic syndrome (35%). Of all, 77% of the patients were vaccinated, and half of them received a booster. At 28 days after the breakthrough COVID-19 diagnosis, 35 (20%) subjects required hospital admission. Out of those patients, seven (4%) died during the follow-up due to the progression of COVID. Our results corroborate what has been established to date with regard to the positive clinical and safety outcomes of MOL in haematology patients with mild or moderate COVID-19.
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COVID-19 , Neoplasias Hematológicas , Humanos , Teste para COVID-19 , SARS-CoV-2 , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológicoRESUMO
Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.
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Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , COVID-19 , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B , Mieloma Múltiplo , Humanos , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Leucemia Linfocítica Crônica de Células B/imunologia , Mieloma Múltiplo/imunologia , SARS-CoV-2 , Hospedeiro Imunocomprometido/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/imunologiaRESUMO
A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are cytokines belonging to the tumor necrosis factor family which play an essential role in B-cell maturation, differentiation, and survival. Recent evidence indicates their importance in hematological disorders; however, their function in essential thrombocytosis (ET) pathogenesis remains elusive. Therefore, we aimed to analyze the role of APRIL and BAFF in megakaryocytopoiesis in ET patients. We observed elevated levels of APRIL and BAFF in the plasma of ET patients compared with healthy controls, while no differences were found among patients with different JAK2(V617F) statuses. In addition, APRIL levels were positively associated with the number of platelets and WBC count. In the bone marrow, APRIL but not BAFF levels were higher in ET patients with the JAK2(V617F) mutation; however, JAK2(V617F)-negative patients showed slightly reduced levels of BAFF. In ET patients, we showed that the differentiation of CD34+ progenitor cells towards megakaryocytes induces the expression of both APRIL and BAFF. More importantly, APRIL neutralization significantly reduced platelet production. In conclusion, our data provide evidence that blocking APRIL signaling, which acts as an autocrine growth factor for terminal megakaryocytopoiesis, inhibits platelet production in ET patients, regardless of the status of JAK2(V617F) mutation.
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The risk of a hemolytic reaction during the transfusion of ABO non-identical PC is determined by the presence of natural anti-A IgM antibodies, the titer of which may increase after infections. The aim of the study was to evaluate the titer of anti-A isohemagglutinins in platelet concentrate (PC) obtained by apheresis from group O donors who experienced SARS-CoV-2 infection, and to compare the titer before and after infection. A retrospective single-center analysis of 21 PC donors with a previous COVID-19 history was performed. The results showed neither a statistically important increase in the anti-A IgM antibody titers nor a significant correlation between the anti-A IgM antibody level and anti-SARS-CoV-2S1 antibody titer in the donors with an asymptomatic or mild COVID-19. Further population-based studies on anti-A titers are necessary for a comprehensive assessment of this phenomenon.
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COVID-19/sangue , COVID-19/imunologia , Hemaglutininas/sangue , Plaquetoferese , SARS-CoV-2 , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Anticorpos Antivirais/sangue , Doadores de Sangue , Estudos de Coortes , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2/imunologia , Reação Transfusional/sangue , Reação Transfusional/etiologia , Reação Transfusional/imunologia , Adulto JovemRESUMO
Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC.
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In the field of transfusion medicine, many pathogen reduction techniques (PRTs) are currently available, including those based on photochemical (PI) and photodynamic inactivation (PDI). This is particularly important in the face of emerging viral pathogens that may pose a threat to blood recipients, as in the case of the COVID-19 pandemic. However, PRTs have some limitations, primarily related to their adverse effects on coagulation factors, which should be considered before their intended use. A comprehensive search of PubMed, Wiley Online Library and Science Direct databases was conducted to identify original papers. As a result, ten studies evaluating fresh plasma and frozen-thawed plasma treated with different PI/ PDI methods and evaluating concentrations of coagulation factors and natural anticoagulants both before and after photochemical treatment were included in the review. The use of PI and PDI is associated with a significant decrease in the activity of all analysed coagulation factors, while the recovery of natural anticoagulants remains at a satisfactory level, variable for individual inactivation methods. In addition, the published evidence reviewed above does not unequivocally favour the implementation of PI/PDI either before freezing or after thawing as plasma products obtained with these two approaches seem to satisfy the existing quality criteria. Based on current evidence, if implemented responsibly and in accordance with the current guidelines, both PI and PDI can ensure satisfactory plasma quality and improve its safety.
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Segurança do Sangue , COVID-19/epidemiologia , Pandemias , Plasma , SARS-CoV-2 , HumanosRESUMO
INTRODUCTION: Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed. AIMS: To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platelet and blood coagulation activation. MATERIAL AND METHODS: 32 patients without previous indications for dual antiplatelet therapy (mean age 78.5±7.9 years, 62% females) with severe aortic valve stenosis (mean gradient 54.6±16.9mmHg) who qualified for TAVI procedure (Edwards Sapien XT) were prospectively analyzed. Platelet counts were analyzed before the surgery, on the day of the procedure and for the three following postoperative days (POD 1 to 3). To assess platelet activation P-selectin (PS, serum) and platelet factor 4 (PF-4, CTAD plasma) were measured, whereas for the evaluation of coagulation activation prothrombin fragments 1+2 (F1+2, plasma) were assessed before the procedure, on POD-1 and POD-3 (ELISA). RESULTS: During the postoperative period a significant platelet count drop, the most evident on POD-2, was observed followed by a platelet count raise. The platelet count drop correlated directly with the amount of iodinated contrast agent (r=0.42, p=0.016) and inversely with baseline mean platelet volume (r=-0.37, p=0.046). Neither clinical nor perioperative parameters, except contrast medium, influenced platelet count decrease. No significant differences regarding the concentration of the evaluated markers in patients with and without thrombocytopenia were found. PF-4 and F1+2 significantly changed during the study (p<0.05). Greater acute PF-4 decrease correlated with greater acute platelet count drop (r=0.48, p=0.043), and during the study slower PF-4 increase correlated with higher platelet count increase on POD-3 (r=-0.505, p=0.032). Lower baseline PS correlated with lower baseline platelet count and higher platelet count increase on POD-3 (r=0.45, p=0.04 and =-0.55, p=0.02, respectively). No significant correlations between F1+2 concentrations and platelet count changes have been found. CONCLUSIONS: Platelet reduction shortly after TAVI procedure is related to the amount of contrast agent applied during the procedure. Platelet activation and blood coagulation along with impaired baseline platelet renewal might be the mechanisms of thrombocytopenia following TAVI procedure.
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Trombocitopenia/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Trombocitopenia/sangue , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
Thrombocytopenia (TP) following transcatheter aortic valve implantation (TAVI) procedure is a common phenomenon but the underlying mechanisms are neither well known nor described. Postinterventional severe TP is related to worse early and late outcome. Moreover, the statement of enhanced platelet and coagulation activation might justify even stronger antiplatelet and anticoagulation therapy following TAVI procedure. Thus, the examination of the pathomechanisms responsible for TP post TAVI seems to be crucial. Several hypotheses have been raised. TP can be caused by insufficient production or impaired platelet renewal. On the other hand, increased platelet activation, consumption and destruction might also be responsible for TP. These findings, mostly related to the procedure alone, need further investigation. Here, we summarize the potential multifactorial causes of post TAVI thrombocytopenia.
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Trombocitopenia/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Humanos , Fatores de RiscoRESUMO
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.
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Cladribina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/farmacologia , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução/métodos , Cariotipagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Polônia , Indução de RemissãoRESUMO
In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples with an independent analytical technique. Linoleamide (p = 0.002) in addition to various acylcarnitines (p = 0.001-0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p = 0.05) and hexannoylcarnitine (p = 0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a potentially highly specific and sensitive diagnostic approach (AUC = 0.766).
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Biomarcadores Tumorais/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Metabolômica/métodos , Carnitina/análogos & derivados , Carnitina/sangue , Feminino , Humanos , Ácidos Linoleicos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: The purpose of the study was the assessment of the expression of IL-1ß and IL-6, and the proteins regulating their biological activity, namely IL-1RII, IL-1Ra, as well as sIL-6Rα, sgp-130 in leukemic lymphocytes and autologous neutrophils of B-CLL patients. MATERIAL/METHODS: The study involved a group of B-cell chronic lymphocytic leukemia patients and healthy volunteer blood donors. The presence of chosen proteins and their natural regulators was confirmed by Western blot. RESULTS: Western blot analysis showed a decreased expression of IL-1ß and IL-6 in the leukocytes of B-CLL patients. Decreased expression of sIL-6Rα has been observed in lymphocytes, with a simultaneous increase of expression in PMNs. Lower expression of sgp-130 was found in B cells while its expression was elevated in the neutrophils of patients in early stages of the disease. CONCLUSIONS: The changes observed in the expression of IL-1 and IL-6 seem to exclude their immediate involvement in the progress of B-CLL. However, the presented changes in the expression of proteins regulating IL-1ß and IL-6 in PMNs indicate a potential role of early immune response cells also in advanced stages of the disease.
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Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Recent studies in a mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of the programmed death receptor 1 (PD1)-PDL1 axis resulted in correction of leukemiainduced CD8+ T cellrelated immune dysfunction and protected mice against CLL development. However, it remains unclear whether CLL development and progression can be also associated with CD4+ T cells expressing PD1. OBJECTIVES: We aimed to analyze whether a quantitative assessment of CD4+PD1+ T cells performed at the time of diagnosis can have prognostic significance in patients with CLL. PATIENTS AND METHODS: We examined 56 patients with newly diagnosed CLL at different stages of the disease. The quantitative assessment of PD1expressing CD4+ T cells was performed in all patients, using multicolor flow cytometry. RESULTS: We demonstrated that CLL patients with an advanced (high and intermediate risk) stage had a significantly higher number of CD4+PD1+ T cells compared with subjects with lowgrade disease. Importantly, we showed that the number of PD1expressing CD4+ T cells in the peripheral blood of patients referred for immediate treatment due to the advanced stage of the disease was significantly higher compared with subjects on watchful waiting. Finally, we found that treatmentnaive patients with higher numbers of CD4+PD1+ T cells at baseline showed a significantly shortened time to the first treatment compared with patients with a low number of CD4+PD1+ T cells. CONCLUSIONS: Our study showed that the quantative assessment of CD4+PD1+ T cells in peripheral blood using flow cytometry can facilitate prognostication of patients with newly diagnosed CLL.
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Linfócitos T CD4-Positivos/metabolismo , Expressão Gênica , Leucemia Linfocítica Crônica de Células B/metabolismo , Receptor de Morte Celular Programada 1/genética , Idoso , Linfócitos T CD4-Positivos/patologia , Progressão da Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Three main monocyte subsets: classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++, differentially regulate tumor growth and survival. Thereby, in the present study we aimed to determine the role of distinct monocyte subsets in the prognostication of chronic lymphocytic leukemia (CLL). Moreover, we set out to analyze the effects of standard immune chemotherapy on different monocyte subsets and levels of membrane-associated and soluble forms of CD163, a monocyte/macrophage-related immunomodulatory protein. We demonstrated that the number of peripheral blood classical CD14++CD16- monocytes assessed at the time of diagnosis was negatively correlated with lymphocytosis and was decreased in the CLL patients who required immediate treatment as opposed to patients who qualified to 'watch and wait' strategy. Notably, lower baseline levels of classical CD14++CD16- monocytes in CLL patients who were qualified for 'watch and wait' therapy were associated with shorter time to initial treatment. Notably, therapy with rituximab, cyclophosphamide and fludarabine resulted in a significant reduction in the number of non-classical CD14+CD16++ monocytes and soluble form of CD163 but upregulation of membrane-associated monocyte CD163. Our data indicate that distinct monocyte subsets and two forms of CD163 are differentially modulated by both CLL and immune chemotherapy. Moreover, we proposed that quantification of classical monocytes at the time of diagnosis contributes to better prognostication of CLL patients.
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Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores de Lipopolissacarídeos/sangue , Receptores de Superfície Celular/sangue , Receptores de IgG/sangue , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Contagem de Células , Linhagem da Célula/genética , Ciclofosfamida/administração & dosagem , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Humanos , Fatores Imunológicos/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/patologia , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Receptores de Superfície Celular/imunologia , Receptores de IgG/imunologia , Rituximab/administração & dosagem , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB.
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Mieloma Múltiplo/genética , Fator de Necrose Tumoral alfa/sangue , Idoso , Apoptose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
This prospective study estimated outcomes in 509 elderly patients with acute myeloid leukemia (AML) with different treatment approaches depending on Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI). Patients were stratified into fit (ECOG 0-2 and CCI 0-2) or frail (ECOG>2 and/or CCI>2) groups. Fit patients with CCI 0 received intensive chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with CCI 1-2. Frail patients received best supportive therapy. Fit patients presented a longer overall survival (OS) than frail subjects, but 8-week mortality rates were similar. The complete response (CR) rate between fit CCI 0 and CCI 1-2 subgroups was significantly different. Both of the fit subgroups showed similar 8-week mortality rates and OS probabilities. Allocating fit patients with CCI 1-2 to R-IC enabled an increase in the group of elderly patients who could be treated with the intention of inducing remission.
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Leucemia Mieloide Aguda/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Polônia/epidemiologia , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
Using patients with polycythemia vera (PV) as an experimental model, we evaluated the impact of clot retraction (CR) and architecture of the clot on fibrinolysis. We studied the kinetics of clot retraction and the fibrinolysis rate in whole blood from 48 PV patients and 48 healthy controls. Measurements were performed before and after isovolemic eryhrocytapheresis (ECP). CR was measured by optical method. Clot lysis time (CLT) and maximum clot firmness (MCF) were measured by thromboelastometry in recalcified blood supplemented with t-PA and tissue factor. Compared with healthy controls, CR rate in PV patients was higher (0.0219 vs. 0.0138; p<0.001), the clot volume smaller and MCF elevated (64 vs. 58 mm). CR rate correlated with platelet count (r=0.546; p=0.001) but not with erythrocyte concentration (r=0.192; p>0.3). Compared with healthy controls, CLT in PV patients was significantly prolonged (158 min vs. 71 min). Fibrinolysis rate inversely correlated with CR rate (r=-0.566; p<0.001); MCF (r=-0.704; p<0.001) and platelet count (r=-0.461; p<0.001). As judged by confocal microscope, in comparison to healthy controls, clots formed in blood from PV patients demonstrated booth a distinctly higher degree of crosslinking and possessed thinner fibers. Altered CR, MCF and fibrinolysis speeds were not normalized following the ECP procedure. Tirofiban (a blocker of platelet GPIIb/IIIa receptors), unlike aspirin, normalized abnormal CR and fibrinolysis in blood from PV patients. Collectively, our data indicate that in PV patients, abnormal CR may result in formation of thrombi that are more resistant to fibrinolysis. ECP and aspirin failed to normalize platelet-related fibrinolysis resistance.
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Remoção de Componentes Sanguíneos/métodos , Plaquetas/metabolismo , Retração do Coágulo/fisiologia , Eritrócitos/patologia , Fibrinólise/fisiologia , Policitemia Vera/sangue , Policitemia Vera/terapia , Adulto , Idoso , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Citaferese/métodos , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Heat shock proteins (HSPs) are overexpressed in many types of cancers and are implicated in tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. It has been postulated that the HSP70 protein can be used as a prognostic indicator of overall patient survival in many types of cancer including leukemia. OBJECTIVES: The aim of the study was to evaluate the concentrations of antiHSP70 antibody and its antigen in the peripheral blood of patients with acute myeloid leukemia (AML), as well as to assess the usefulness of this measurement. PATIENTS AND METHODS: The study included 80 patients with AML of intermediate and high cytogenetic risk, scheduled for allogenic stem cell transplantation after initial intensive chemotherapy. Plasma concentrations of antiHSP70 antibodies and HSP70 antigen were measured by enzymelinked immunosorbent assay. The antigen was additionally measured by Western blot analysis. The control group consisted of healthy subjects. RESULTS: Patients with AML had significantly higher antiHSP70 antibody concentrations compared with the control group. The concentration of HSP70 antigen as well as antiHSP70 antibody showed no associations with the type of response after induction chemotherapy. However, patients with higher antigen levels and lower antiHSP70 antibody levels had significantly shorter overall survival. CONCLUSIONS: The study suggests that antiHSP70 antibodies and HSP70 antigen may be valuable indicators of a poor prognosis in patients with AML.
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Anticorpos/sangue , Antígenos/sangue , Biomarcadores Tumorais/sangue , Proteínas de Choque Térmico HSP70/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Prognóstico , Taxa de SobrevidaRESUMO
Long-term outcomes following newer therapies for chronic lymphocytic leukemia (CLL) have rarely been reported. This article presents the results of the final analysis of the Polish Adult Leukemia Group PALG-CLL2 study performed 10 years from final patient enrollment. With the extended follow-up time, it was found that cladribine (2-CdA)-based combinations CMC (2-CdA, cyclophosphamide, mitoxantrone) and CC (2-CdA, cyclophosphamide) administered as first-line treatment of progressive CLL resulted in significantly longer progression-free survival, but similar overall survival compared to 2-CdA monotherapy. Furthermore, the risk of potentially fatal late adverse events including infections, autoimmune complications and, particularly, secondary neoplasms was comparable among patients treated with CMC, CC or 2-CdA. The results of our analysis support the importance of long-term outcome monitoring of randomized trials in CLL.