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1.
Am J Hematol ; 95(12): 1562-1571, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32936982

RESUMO

Hyperdiploidy (HRD) and specific immunoglobulin heavy locus (IGH) translocations are primary chromosomal abnormalities (CA) in multiple myeloma (MM). In this retrospective study of 794 MM patients we aimed to investigate clinical features and common CA including gain(1q) in separate subgroups defined by primary CA. In the entire group, we confirmed that gain(1q) was associated with short time to next treatment and adverse overall survival (OS). The impact was worse for four or more copies of 1q21 as compared to three copies. However, in a subgroup of patients with clonal gain(11q) and without known primary IGH translocations (CG11q), already three copies of 1q21 were associated with a poor outcome; in the absence of gain(1q), patients in this subgroup had a remarkably long median OS of more than nine years. These cases were associated with HRD, coexpression of CD56 and CD117, male gender, and IgG subtype. In non-CG11q patients, four or more copies of 1q21 (but not three copies) had a significant adverse impact on outcome. Several associations with CA and clinical findings were observed for the defined subgroups. As an example, we found a predominance of early tetraploidy, plasma cell leukemia, and female gender in the t(14;16) subgroup. Our results underscore the importance of subgrouping in MM.


Assuntos
Cromossomos Humanos Par 1/genética , Loci Gênicos , Cadeias Pesadas de Imunoglobulinas/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Proteínas de Neoplasias/genética , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CD56/genética , Intervalo Livre de Doença , Feminino , Humanos , Imunoglobulina G/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Proteínas Proto-Oncogênicas c-kit/genética , Taxa de Sobrevida
2.
Wien Klin Wochenschr ; 131(1-2): 47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30542777

RESUMO

Correction to:Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1365-5 The original version of this article unfortunately contained a mistake. Table Nr. 1 was inconsistent. The corrected version of Table 1 is given below. We apologize for any inconveniences this may have ….

3.
Wien Klin Wochenschr ; 130(17-18): 535-542, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30027395

RESUMO

Polycythemia vera (PV) is a clonal disease arising from hematopoietic stem cells. Erythrocytosis is the hallmark of the disease but leukocytosis, thrombocytosis and splenomegaly may also be present. Thromboembolic complications occur in about 20% of patients. Circulatory disturbances as well as pruritus represent frequent symptoms of the disease. Mutations in the JAK2 gene are present in 95% of patients in exon 14 (V617F) and in 3% in exon 12. The main goal of the treatment for patients with PV is the prevention of thromboembolic events, transformation to myelofibrosis and acute myeloid leukemia. Interferon alpha and hydroxyurea are used as first-line treatment for high risk patients. For patients unresponsive to first-line therapy ruxolitinib is available.


Assuntos
Policitemia Vera , Mielofibrose Primária , Trombocitose , Áustria , Feminino , Humanos , Janus Quinase 2/genética , Masculino , Policitemia Vera/diagnóstico , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Trombocitose/prevenção & controle
4.
Wien Klin Wochenschr ; 130(17-18): 495-504, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30043249

RESUMO

The oral Janus associated kinase (JAK1/2) inhibitor ruxolitinib has been available for treatment of patients with intermediate or high-risk myelofibrosis in Europe since 2012. Since its introduction, the expertise of prescribing doctors with respect to ruxolitinib function, efficacy and adverse effects has consistently been augmented, resulting in therapy modalities that are better tailored to individual patients as well as in increased safety of the treatment. The present consensus on ruxolitinib therapy management has been elaborated by Austrian experts in myeloproliferative neoplasms in line with international treatment guidelines. Our recommendations aim to contribute to an improved management of patients with myelofibrosis treated with ruxolitinib.


Assuntos
Mielofibrose Primária , Pirazóis/uso terapêutico , Áustria , Consenso , Europa (Continente) , Humanos , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirimidinas , Estudos Retrospectivos
5.
Eur J Haematol ; 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29603799

RESUMO

OBJECTIVES: Risk of thrombosis is significantly enhanced by both elevated platelet (PLT) and white blood cell (WBC) counts according to a retrospective analysis of a large anagrelide registry in thrombocythemic MPN patients. We were interested in the impact of elevated WBC counts on thrombosis risk in patients where PLT counts were reduced below the calculated cutoff of 574.5 G/L by treatment with anagrelide. METHODS: Cox regression analysis and Kaplan-Meier plot were applied on all patients in the registry with optimized PLT counts. RESULTS: Using the calculated cutoff of 9.66 G/L for WBC, Cox regression analysis revealed a clear influence of elevated WBC counts on the occurrence of a major thrombotic event (P = .012). A Kaplan-Meier plot revealed a markedly shorter time to a major thrombotic event for patients with WBC counts above the cutoff (P = .001). CONCLUSIONS: These data suggest that additional correction of elevated WBC counts is mandatory in patients with optimally managed PLT counts to reduce thrombotic risk. This study is the first investigation in a prospectively observed large patient cohort which was treated homogenously allowing for evaluation of single parameters for an effect on thrombophilia.

6.
Oncol Res Treat ; 41(4): 188-193, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29562227

RESUMO

Angiogenesis is a hallmark of cancer and is regulated by a balance of pro- and anti-angiogenic factors; among them, the vascular endothelial growth factor (VEGF) is the key angiogenic factor. VEGF plays an important role in colorectal cancer (CRC) biology, and its inhibition by using bevacizumab, an anti-VEGF antibody, proved for the first time to be effective and became indispensable for the treatment of metastatic CRC (mCRC). Several large phase III studies showed also relevant responses and tolerability of other anti-angiogenic drugs such as ramucirumab, aflibercept, and regorafenib, and led to the approval of these therapeutics. Nevertheless, the efficacy of anti-angiogenic therapies is rather limited and the high expectations raised by preclinical studies were not fulfilled in the clinics. Furthermore, to date, no predictive biomarkers for anti-angiogenic agents could be identified and validated. Thus, new mechanisms of action are discussed, such as tumor vasculature normalization to improve the accessibility of tumor tissue by drugs or to promote tumor infiltration by host immune cells. Cellular and molecular studies will be necessary to characterize the dynamic changes of the tumor microenvironment and the vascular architecture in individual patients in order to predict responsiveness to anti-angiogenic therapies. In this review, we tried to highlight the standard of care of using anti-angiogenics in mCRC patients and to provide an outlook on potential new substances and strategies.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores da Angiogênese/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/análise , Ensaios Clínicos Fase III como Assunto , Colo/irrigação sanguínea , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Humanos , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/patologia , Seleção de Pacientes , Inibidores de Proteínas Quinases/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto/irrigação sanguínea , Reto/efeitos dos fármacos , Reto/patologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Cancer Sci ; 109(5): 1583-1591, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29498788

RESUMO

Nivolumab belongs to the standard therapy in the second-line setting of metastatic renal cell carcinoma (mRCC). Although deep and long-lasting responses are seen in some patients, the majority of patients will further progress. PD-L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO-1, a negative immune-regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO-1 and other immune inhibitory molecules (PD-L1, PD-L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin-fixed, paraffin-embedded sections of RCC specimens by immunohistochemistry. IDO-1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO-1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non-responders (33.3%, n = 3/9; P = .028), resulting in a better progression-free survival during immunotherapy (IDO-1 ≤ 10% vs >10%, median: 3.5 vs not estimated (NE) months, P = .01 by log-rank test). In addition, IDO-1 was positively correlated with CD8+ T cell expression (rs = .691, P = .006). PD-L1 expression on tumor cells was negative in 13 (86.7%) of 15 patients, irrespective of therapeutic response (responders vs non-responders: 83.3% vs 88.9%). No differences were noticed in the PD-L1 expression on tumor-infiltrating immune cells (PD-L1 < 1% in 66.7% of both responders and non-responders). In contrast to PD-L1, these results suggest that IDO-1 may be a more promising predictive biomarker for response to immune-based cancer therapy in mRCC.


Assuntos
Carcinoma de Células Renais/terapia , Células Endoteliais/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/fisiologia , Neoplasias Renais/terapia , Idoso , Antígeno B7-H1/análise , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Feminino , Humanos , Imunoterapia , Neoplasias Renais/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade
8.
Intern Med J ; 47(10): 1173-1183, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28707749

RESUMO

BACKGROUND: Entry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn-based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS. AIM: To study the relationships between endothelial extracellular vesicles (EV) and plasminogen-activator inhibitor type 1(PAI-1) to assess their modification in the early phase of SOS. METHODS: Consecutive blood samples were tested for cell-derived EV, PAI-1 and coagulation parameters. Any statistically significant correlation between all datasets was searched. RESULTS: Antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI-1:Ag and PAI-1:act showed an inverse relationship with platelet counts (coef. -0.034, SE = 0.016; P = 0.041 and -0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI-1:Ag was inversely related to EV CD144+ (coef. -0.261, SE = 0.094; P = 0.007) and antithrombin (coef -0.509, SE = 0.175; P = 0.005). PAI-1:act showed an inverse association with EV CD144+ (coef.-0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. -0.004, SE = 0.002; P = 0.026) and antithrombin (coef. -0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time. CONCLUSION: This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI-1, as a new biomarker for SOS.


Assuntos
Endotélio Vascular/metabolismo , Vesículas Extracelulares/metabolismo , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/diagnóstico , Inibidor 1 de Ativador de Plasminogênio/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Hepatopatia Veno-Oclusiva/terapia , Humanos , Masculino , Transplante Autólogo/tendências
9.
J Cancer Res Clin Oncol ; 143(8): 1585-1596, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28364360

RESUMO

PURPOSE: Achievement of deep molecular response with a tyrosine kinase inhibitor in patients with chronic myeloid leukemia (CML) is required to attempt discontinuation of therapy in these patients. The current subanalysis from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study evaluated whether age has an impact on the achievement of deeper molecular responses or safety with frontline nilotinib in patients with CML. METHODS: ENEST1st is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed CML in chronic phase. The patients were stratified into the following 4 groups based on age: young (18-39 years), middle age (40-59 years), elderly (60-74 years), and old (≥75 years). The primary end point was the rate of molecular response 4 ([MR4] BCR-ABL1 ≤0.01% on the international scale) at 18 months from the initiation of nilotinib. RESULTS: Of the 1091 patients enrolled, 1089 were considered in the analysis, of whom, 23% (n = 243), 45% (n = 494), 27% (n = 300), and 5% (n = 52) were categorized as young, middle age, elderly, and old, respectively. At 18 months, the rates of MR4 were 33.9% (95% confidence interval [CI], 27.8-40.0%) in the young, 39.6% (95% CI, 35.3-44.0%) in the middle-aged, 40.5% (95% CI, 34.8-46.1%) in the elderly, and 35.4% (95% CI, 21.9-48.9%) in the old patients. Although the incidence of adverse events was slightly different, no new specific safety signals were observed across the 4 age groups. CONCLUSIONS: This subanalysis of the ENEST1st study showed that age did not have a relevant impact on the deep molecular response rates associated with nilotinib therapy in newly diagnosed patients with CML and eventually on the eligibility of the patients to attempt treatment discontinuation.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Resultado do Tratamento
10.
Transl Res ; 184: 21-34, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28259616

RESUMO

Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition. We hypothesized that treatments for reducing PLT count might also indirectly affect MP generation and endothelial activity by altering endothelial modulator production. The rationale of this study was that hydroxyurea (HU), a cytostatic drug largely used in ET, induces the production of a potent vasoactive agent NO in ECs. An observational retrospective study was designed to investigate the relationship between MPs, NO, ADM, and ET-1 in ET patients on treatment with HU, anagrelide (ANA), aspirin (ASA), and a group of patients before treatment. A total of 63 patients with ET diagnosis: 18 on HU + ASA, 15 on ANA + ASA, 19 on ASA only, and 11 untreated patients, and 18 healthy controls were included in this study. Blood samples were analyzed for MP (absolute total values) and functional markers (percentage values) by flow cytometry. PLT-derived MPs were studied using CD61, CD62P, CD36, and CD63, whereas endothelial-derived MPs were studied using CD105, CD62E, and CD144. Endothelial modulator markers (NO, ADM, and ET-1) were measured by ELISA. Total MP count was higher in the group treated with ANA + ASA (P < 0.01). MP markers modified in ET patients returned to levels of healthy controls following treatment, in particular, in patients on ANA treatment. NO and ADM values were higher in the HU group (P < 0.001). HU and ANA treatment also affected MP production in a cell origin-specific manner. HU and ANA, although acting via different pathways, have similar final effects. For instance, HU causes vasodilatation by increasing NO and ADM levels, whereas ANA impairs vasoconstriction by reducing ET-1. In conclusion, therapy with HU cytostatic drugs and ANA can reduce PLT count in ET, and also affect endothelial modulatory agents, with HU sustaining vasodilation and prothrombotic MP concentration, whereas ANA decreases vasoconstriction.


Assuntos
Endotélio Vascular/patologia , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/fisiopatologia , Adrenomedulina/sangue , Adrenomedulina/metabolismo , Idoso , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Estudos de Casos e Controles , Micropartículas Derivadas de Células/patologia , Endotelina-1/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Hidroxiureia/uso terapêutico , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Trombocitemia Essencial/sangue
11.
J Clin Oncol ; 35(2): 175-184, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28056193

RESUMO

Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts. Results T cells of patients with CML at diagnosis expressed low l-selectin (CD62L) levels, which was not a result of proportional aberrations of T-cell subsets. Low numbers of CD62L-expressing CD4+ and CD8+ T cells correlated with higher Sokal score, increased spleen size, and high leukocyte and peripheral-blood blast counts. At month 6 during nilotinib therapy, CD62L expression returned to levels of healthy individuals. The level of CD62L loss on T cells directly correlated with the extent of soluble CD62L (sCD62L) elevation. In parallel, the proteolytic activity of tumor necrosis factor α-converting enzyme (TACE; ADAM17, CD156b), the metalloproteinase shedding CD62L, was increased at diagnosis and significantly decreased during nilotinib treatment. High CD62L+ expression on both CD4+ and CD8+ T cells and, vice versa, low sCD62L levels at CML diagnosis were linked to superior molecular responses. These findings were corroborated in independent validation cohorts. Conclusion We demonstrate the prognostic impact of CD62L shedding from T cells and increased sCD62L plasma levels at CML diagnosis on molecular response to tyrosine kinase inhibitor therapy in early chronic-phase CML. Functionally, decreased CD62L may be a consequence of increased TACE-mediated CD62L cleavage and potentially impairs immune-cell function. Larger prospective studies are ongoing to confirm the prognostic relevance of this finding.


Assuntos
Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Vigilância Imunológica/imunologia , Selectina L/análise , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Linfócitos T/imunologia , Proteína ADAM17/análise , Citometria de Fluxo , Humanos , Prognóstico , Estudos Prospectivos
12.
Wien Klin Wochenschr ; 129(9-10): 293-302, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27966016

RESUMO

The entity "myelofibrosis" represents a subgroup of the Philadelphia chromosome-negative myeloproliferative neoplasms. It comprises primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. This heterogeneous disease is characterized by clonal myeloproliferation, dysregulated kinase signalling and the abnormal expression of several proinflammatory cytokines. Clinically, patients present with symptoms related to thrombocytosis/leukocytosis, anemia and/or progressive splenomegaly. Mutations in Janus kinase 2, an enzyme that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 60% of patients with primary myelofibrosis. Recent molecular advances have not only elucidated critical pathways in the pathogenesis of the disease, but also contributed to a more precise assessment of a patient's individual risk. While allogeneic stem cell transplantation remains the only curative treatment, the natural course of the disease and the patient's survival and quality of life may be improved by new treatments, notably ruxolitinib, the first Janus kinase 1/2 inhibitor approved for the management of myelofibrosis. Additional treatment options are being explored.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Prova Pericial , Hematologia/normas , Terapia de Alvo Molecular/métodos , Guias de Prática Clínica como Assunto , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Áustria , Mielofibrose Primária/patologia
13.
Blood Transfus ; 15(4): 333-340, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27483482

RESUMO

Chronic wounds, such as diabetic foot ulcers, represent a serious clinical problem for patients and clinicians. Management of these wounds has a strong economic impact worldwide. Complications resulting from injuries are a frequent cause of morbidity and mortality. Chronic wounds lead to infections, painful dressings and prolonged hospitalisation. This results in poor patient Quality of Life and in high healthcare costs. Platelet concentrates (PC) are defined as autologous or allogeneic platelet derivatives with a platelet concentration higher than baseline. PC are widely used in different areas of Regenerative Medicine in order to enhance wound healing processes; they include platelet-rich plasma (PRP), platelet gel (PG), platelet-rich fibrin (PRF), serum eye drops (E-S), and PRP eye drops (E-PRP). This review highlights the use of platelet-rich plasma (PRP) and platelet gel (PG) preparation for clinical use.


Assuntos
Plaquetas , Pé Diabético/tratamento farmacológico , Fibrina Rica em Plaquetas , Géis , Humanos
14.
Oncol Res Treat ; 39(12): 796-802, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27889786

RESUMO

Over the past decades, considerable progress has been made in the management of colorectal cancer (CRC), leading to a significant improvement in overall survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of CRC and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article, we will discuss various targeted therapies in the management of metastatic CRC (mCRC). In particular, vascular endothelial growth factor (VEGF)- and epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies have become integral components of the first-line treatment strategies for mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well. Currently, the only predictive biomarker for treatment selection in patients with mCRC is tumor RAS mutational status.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Terapia de Alvo Molecular/tendências , Proteínas de Neoplasias/imunologia , Anticorpos Monoclonais/imunologia , Antineoplásicos/imunologia , Medicina Baseada em Evidências , Humanos , Resultado do Tratamento
15.
Regen Med ; 11(5): 459-63, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27346565

RESUMO

AIM: Bone osteoradionecrosis is a serious complication of radiation treatment. Current treatment approaches are not curative and treatment response is often poor leading to high social and healthcare costs. CASE REPORT: We report on the first case of osteoradionecrosis with successful restitutio ab integro by repeated administration of platelet gel (PLT-gel) and surgery in a critically ill patient. The administration of PLT-gel during a severe septic episode helped regeneration of bone and soft tissues, shortening the hospital stay of the patient. It was also noted that following applications of PLT-gel, both the use of morphine and the numbers of infective episodes were reduced. CONCLUSION: Additional studies are needed to confirm the promising effect of PLT-gel for the treatment of osteoradionecrosis.


Assuntos
Doenças Mandibulares/terapia , Osteorradionecrose/terapia , Plasma Rico em Plaquetas , Doenças do Tecido Conjuntivo/terapia , Fístula/terapia , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Transfusão de Plaquetas , Regeneração , Medicina Regenerativa , Cicatrização
16.
Eur J Haematol ; 97(6): 511-516, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27037858

RESUMO

OBJECTIVES: Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms. METHODS: This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed. RESULTS: Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient-years was highest (P = <0.001) when both platelet and WBC counts ranged above the calculated cutoffs. CONCLUSION: Our data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts.


Assuntos
Plaquetas , Contagem de Leucócitos , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombose/sangue , Trombose/etiologia , Idoso , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Quinazolinas/uso terapêutico , Sistema de Registros , Medição de Risco , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/epidemiologia , Trombose/tratamento farmacológico , Trombose/epidemiologia
17.
Anticancer Res ; 35(9): 5129-39, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26254418

RESUMO

Bendamustine is an established treatment option in chronic lymphocytic leukemia (CLL) and frequently used in Austria and Italy. Therefore, we analyzed 100 unselected, consecutive patients with CLL (treatment-naïve and relapsed/refractory) receiving bendamustine in a real-life setting. Most patients were treated with bendamustine in combination with rituximab (BR). However, bendamustine monotherapy was additionally evaluated. Patients treated with BR had a significantly higher overall response rate of 76% (complete response=22%) when compared to those treated solely with bendamustine (overall response rate=50%; complete response=13%). Overall survival (OS) and progression -ree survival (PFS) were significantly lower in the bendamustine-treated group (OS=14.3 months; PFS=8.3 months) compared to the BR group (OS=42.7; PFS=22.5 months; both p<0.001). In multivariate analysis, patients with a good cytogenetic risk and those receiving BR had a significantly better OS. Grade 3/4 hematological complications were seen in 32% of the patients. Hence, bendamustine, especially in combination with rituximab, is an effective therapy with manageable toxicity for non-selected patients with CLL including those pre-treated with fludarabine and the elderly.


Assuntos
Antineoplásicos/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/efeitos adversos , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Análise Multivariada , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento
18.
Leuk Res ; 39(6): 592-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25850727

RESUMO

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases.


Assuntos
Doenças Cardiovasculares , Monitorização Fisiológica , Inibidores da Agregação Plaquetária/administração & dosagem , Quinazolinas/administração & dosagem , Trombocitemia Essencial , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Quinazolinas/efeitos adversos , Trombocitemia Essencial/sangue , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/fisiopatologia , Troponina I/sangue
20.
Intern Emerg Med ; 10(4): 451-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25585678

RESUMO

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 × 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 × 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings.


Assuntos
Contagem de Células Sanguíneas , Hemorragia/etiologia , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombose/etiologia , Adolescente , Adulto , Intervalo Livre de Doença , Seguimentos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Adulto Jovem
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