Kooperativer Bibliotheksverbund

In: International Journal of Hematologic Oncology, Future Medicine Ltd, Vol. 3, No. 1 ( 2014-02), p. 63-70

Abstract: SUMMARY Autologous stem cell transplantation (ASCT), in chemosensitive relapsed patients with Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), is associated with superior event-free survival (EFS) compared with salvage chemotherapy alone. BEAM is one of the most commonly used regimens in both HL and NHL because of its acceptable toxicity and high effectiveness. The nonrelapsed mortality (NRM) ranges from 7 to 10% in historical studies. More recent investigations have demonstrated a lower NRM, probably due to various factors such as the use of peripheral blood precursor cells and better support therapy. Recently, in order to reduce the toxicity of carmustine and increase antilymphoma activity, several groups have introduced conditioning regimens similar to BEAM. The incorporation of newer drugs (anti-CD20 monoclonal antibodies ± radiolabeled) to ‘classic’ BEAM, or the substitution of carmustine with other drugs (thiotepa, bendamustine and fotemustine) may be a valuable strategy in this patient setting. In this review, we will discuss the data available on HDC followed by ASCT in lymphoma using new conditioning regimens, namely second-generation BEAM.

Type of Medium: Online Resource

ISSN: 2045-1393 , 2045-1407

URL: Article

DOI: 10.2217/ijh.13.64

Language: English

Publisher: Future Medicine Ltd

Publication Date: 2014

detail.hit.zdb_id: 2692801-2

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 359-359

Abstract: Abstract 359 Background: Nilotinib is a potent and selective inhibitor of BCR-ABL. In the phase 3 ENESTnd trial, nilotinib demonstrated superior efficacy to imatinib with higher and faster molecular responses. With a median follow-up of 18.5 months (ASCO/EHA 2010), the rates of progression to accelerated or blast phase (AP/BC) were 0.7% and 0.4% with nilotinib 300 mg and 400 mg BID, respectively, and significantly lower in comparison to imatinib (4.2% P = .006 and .003, respectively). Based on the results of the ENESTnd trial, nilotinib has been approved (FDA) for the frontline treatment of Ph+ CML. With imatinib 400 mg (IRIS trial), the rate of any event and the rate of progression to AP/BC were higher during the first 3 years on treatment (15.6% and 6.1%, respectively). Consequently, a confirmation of the durability of nilotinib responses at 3 years is extremely important. Aims: To evaluate responses (either cytogenetic and molecular) and to investigate outcomes of patients treated for 3-years with nilotinib 400 mg BID as frontline therapy. Outcomes evaluated include Overall Survival (OS), Progression-Free Survival (PFS), Failure-Free Survival (FFS) and Event-Free Survival (EFS). Method: A multicentre phase 2 trial (nilotinib 400 mg BID) was conducted by the GIMEMA CML Working Party (ClinicalTrials.gov.NCT00481052). The median follow-up is currently 30 months (3 years by November 2010). Definitions: Major Molecular Response (MMR): BCR-ABL/ABL ratio 〈 0,1% IS; Complete Molecular Response (CMR): undetectable transcript levels and nested PCR negative; failures: no CHR at 3 months, no CgR at 6 months, no PCgR at 1 year, no CCgR at 18 months, loss CHR or CCgR, progression and death (according to the revised European LeukemiaNet recommendations); events: failures and treatment discontinuation for any reason. All the analysis has been made according to the intention-to-treat principle. Result: 73 patients have been enrolled; median age 51 years (range 18–83); 45% low, 41% intermediate and 14% high Sokal risk. The cumulative CCgR rate (primary endpoint) at 12 months was 100%. CCgR at each milestone: 78% at 3 months, 96% at 6, 12 and 18 months, 92% at 24 months. The cumulative rate of MMR was 96%, while the rates of MMR at 3, 6, 12, 18 and 24 months were 52%, 66%, 85%, 81% and 82%, respectively. The cumulative rate of CMR was 41%, while the rates of CMR at 12 and 24 months were 7% and 12%, respectively. None of the patients who achieved a MMR progressed to AP/BC. Only one patient progressed at 6 months to AP/BC: a 63 years old female with a high Sokal risk disease in CCgR at 3 months, who developed a T315I mutation. During the first 12 months, the mean daily dose was 600–800 mg, 400–599 mg, and less than 400 mg in 74%, 18% and 8% of patients, respectively. The nilotinib last daily dose was as follows: 800 mg in 48 (71%) patients, 400 mg in 19 (28%) patients and 200 mg in 1 (1%) patient. Adverse events (AEs) were mostly grade 1 or 2 and manageable with appropriate dose adaptations. Two patients (3%) showed a prolongation of the QTcF above 450 msec (none above 50 msec). Four events lead to permanent discontinuation of nilotinib: 3 patients discontinued after 9, 15 and 27 months on treatment for recurrent episodes of amylase and/or lipase increase (no pancreatitis) and 1 patient after 25 months due to atrial fibrillation, unrelated to study drug. Three of them are currently on imatinib second-line and 1 on dasatinib third-line. Overall, 5 events have been recorded so far (1 progression to AB/BC and 4 permanent discontinuation of nilotinib due to AEs). At 30 months the OS, PFS and FFS are 99% and the EFS is 92%. Conclusion: The rate of failures was very low during the first 3 years. Responses remain stable. The very high rates of responses achieved during the first 12 months on treatment are being translated into optimal outcome for most of the patients. Acknowledgments: European LeukemiaNet, COFIN, Bologna University, BolognAIL Disclosures: Rosti: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau. Castagnetti:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Gugliotta:Novartis: Honoraria. Saglio:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martinelli:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; pfizer: Consultancy. Baccarani:Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding; Wyeth: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.359.359

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2829-2829

Abstract: In essential thrombocythemia (ET) patients, history of thrombosis and age over 60 y are validated risk factors for occurrence of thrombosis during the follow-up. Leukocytosis, JAK2 V617F mutation, cardiovascular (CV) general risk factors, and male gender are candidate risk factors for thrombosis. The thrombocytosis, a constitutive abnormality in ET, is associated with both thrombotic and hemorrhagic complications. Aim To evaluate in a large cohort of ET patients the potential relationship between the thrombosis history and the main clinical and biological characteristics at diagnosis, i.e. before any interference of cytoreductive treatment. Methods A cohort of ET patients (PVSG or WHO criteria) of the Registro Italiano Trombocitemie (RIT) was retrospectively analyzed through logistic regression models. Results A total of 977 patients, 387 males and 590 females, presented at diagnosis: median age 56 y (43% with age 〉 60 y), median PLT count 783 x 109/L (33% with low thrombocytosis, 〈 700 x 109/L), median WBC count 8.8 x 109/L (29% with leukocytosis, 〉 10 x 109/L), median HCT 42.6% (high HCT: 〉 47% in 24% of the males and 〉 44% in 23% of the females), CV general risk factors in 69% of cases (one of smoking, hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, obesity, CV disease, familiarity for thrombosis), bone marrow fibrosis grade 0 in 67% of cases, JAK2 V617F mutation in 56% of the 399 tested patients. The history of thrombosis (arterial in 74% of cases) was reported in 194 (19.9%) patients. The history of thrombosis in univariate analysis was significantly related to: age 〉 60 y (p 0.001), male gender (p 0.009), CV general risk factors (p 0.002), low thrombocytosis (p 0.000), leukocytosis (p 0.003), high HCT (p 0.004), and JAK2 V617F mutation (p 0.008). No relationship was found with bone marrow fibrosis. In multivariate analysis a relationship was confirmed between thrombosis history and age 〉 60 y (p 0.023), male gender (0.046), CV general risk factors (0.039), low thrombocytosis (p 0.004), leukocytosis (0.019), and JAK2 V617F mutation (p 0.033). The rate of thrombosis history in the patients without both low thrombocytosis and leukocytosis (11%, 49/428) resulted significantly lower (p 0.0001) than in the patients with leukocytosis (24%, 54/224), the patients with low thrombocytosis (27%, 71/266), and the patients with both low thrombocytosis and leukocytosis (34%, 20/59). Conclusion In this cohort of ET patients the rate of thrombosis history in multivariate analysis is significantly related to various clinical and biological characteristics at diagnosis, including low thrombocytosis (PLT 〈 700 x 109/L), leukocytosis (WBC 〉 10 x 109/L), JAK2 V617F mutation, age 〉 60 y, male gender, and CV general risk factors. Acknowledgment this study was partially supported by the GIMEMA Foundation (Promotor of the RIT) and by the AIL Foundation. Disclosures: Gugliotta: SHIRE Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.2829.2829

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

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In: Journal of the Neurological Sciences, Elsevier BV, Vol. 186, No. 1-2 ( 2001-5), p. 23-26

Type of Medium: Online Resource

ISSN: 0022-510X

URL: Article

DOI: 10.1016/S0022-510X(01)00495-6

Language: English

Publisher: Elsevier BV

Publication Date: 2001

detail.hit.zdb_id: 1500645-1

In: Cancer Chemotherapy and Pharmacology, Springer Science and Business Media LLC, Vol. 39, No. 1-2 ( 1996-11-18), p. 157-161

Type of Medium: Online Resource

ISSN: 0344-5704 , 1432-0843

URL: Article

DOI: 10.1007/s002800050552

Language: Unknown

Publisher: Springer Science and Business Media LLC

Publication Date: 1996

detail.hit.zdb_id: 1458488-8

SSG: 15,3

In: European Journal of Haematology, Wiley, Vol. 104, No. 6 ( 2020-06), p. 581-587

Abstract: In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed. Results The median number of previous treatments was 2 (1‐4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m 2 on days 1 and 2 of a 21‐day cycle. The median number of BvB cycles was 4 (2‐7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow‐up of 19 months (5‐47), median PFS was 18 months (95%CI: 23‐29), and the 2‐year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G  〉  2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%). Conclusion Our real‐world results suggest that BvB is an effective third‐line rescue and bridge‐to‐transplant regimen for RR‐cHL patients.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.v104.6

DOI: 10.1111/ejh.13400

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1678-1678

Abstract: Abstract 1678 Background. Imatinib mesylate (IM) is the therapeutic standard for chronic myeloid leukemia (CML), but nilotinib and dasatinib, at least in selected patients, have the potential to replace it. The early prediction of poor outcome is important to optimize the treatment strategy. In IM-treated patients, BCR-ABL transcript levels according to the International Scale (IS) 〉 10% at 3 and 〉 1% at 6 months were able to identify high-risk groups (Marin et al, JClinOncol 2011; Hanfstein et al, Leukemia 2012). Similar analysis were performed within the IM arms of the ENESTnd trial (Hochhaus et al, EHA 2012) and the DASISION trial (Jabbour et al, EHA 2012). Methods. To investigate the prognostic impact of BCR-ABLIS levels at 3 and 6 months on the future response status and the long-term outcome of CML patients treated frontline with IM, we analyzed 559 patients enrolled within 3 trials of the GIMEMA CML WP (ClinTrialsGov NCT00514488/NCT00510926, observational trial CML023). Patients with evaluable QPCR sample at 3 and 6 months: 487/559 (87%) and 492/559 (88%), respectively. Definitions: major molecular response (MMR): BCR-ABLIS ratio 〈 0.1%; molecular response with 4.0-log reduction (MR4.0): BCR-ABLIS 〈 0.01%; failures: according to 2009 ELN recommendations. The rate of complete cytogenetic response (CCgR) and MMR at 1 year, the rate of MR4.0 at 2 years, the failure-free survival (FFS), the progression-free survival (PFS) and the overall survival (OS) according to the BCR-ABL transcript levels (≤10% vs 〉 10 and ≤1% vs 〉 1%) at 3 and 6 months were analyzed. Patients with events or censored within 3 or 6 months were excluded from the respective analysis. Receiver operating characteristic (ROC) curves were used for descriptive purposes. Results. Median age: 52 years (range 18–84). IM dose: 76% 400mg, 24% 800mg. Sokal score: 39% low, 39% intermediate, 22% high; EUTOS score: 93% low, 7% high. Median follow-up: 76 months (range: 7–99); 95% of patients had at least 5-year observation. BCR-ABLIS at 3 months: ≤1% in 336/487 (69%), 〉 1% to ≤10% in 120/487 (25%) and 〉 10% in 31/487 (6%). BCR-ABLIS at 6 months: ≤1% in 425/492 (86%), 〉 1% to ≤10% in 54/492 (11%) and 〉 10% in 13/492 (3%). Responses and outcomes according to transcript levels are presented in table 1. Patients with BCR-ABLIS 〉 10% at 3 months achieved inferior CCgR and MMR rates at 1 year and inferior MR4.0 rate at 2 years, but the long-term outcome was comparable to patients with transcript levels 〈 10%. On the contrary, a BCR-ABLIS 〉 1% at 3 months was associated, not only to lower subsequent response rates, but also to significantly inferior FFS, PFS and OS. The BCR-ABLIS levels able to predict for FFS, PFS and OS with maximal sensitivity and specificity (ROC curves) were 1.9%, 0.8% and 0.8%, respectively. Results were similar, with small differences, in the 6-month analysis. Conclusions. In a multicentric nationwide experience, the proportion of patients with BCR-ABLIS transcript levels 〉 10% at 3 and 6 months was low. The risk distribution and the proportion of patients treated with high-dose IM may explain, at least in part, the differences with other published reports. At 3 and 6 months, a BCR-ABLIS cutoff of 1% was a reliable surrogate marker of response and outcome. A transcript level 〉 10% identified a smaller cohort with inferior responses, but failed to predict the long-term outcome. A BCR-ABLIS level 〉 1% at 3 and 6 months represents a warning, requiring a close monitoring. A switch to 2nd generation tyrosine kinase inhibitors should be considered. Acknowledgments. University of Bologna, BolognaAIL, COFIN, Fondazione Carisbo. Disclosures: Castagnetti: Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Novartis Pharma: Consultancy, Honoraria, Speakers Bureau. Gugliotta:Novartis: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria. Breccia:Bristol Myers Squibb: Consultancy; Novartis: Consultancy. Abruzzese:Bristol Myers-Squibb and Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cavazzini:Novartis Pharma: Honoraria; Bristol Myers Squibb: Honoraria. Soverini:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; ARIAD: Consultancy. Saglio:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy. Martinelli:Bristol-Myers-Squibb: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Baccarani:ARIAD, Novartis, Bristol Myers-Squibb, and Pfizer: Consultancy, Honoraria, Speakers Bureau. Rosti:Novartis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Pfizer: Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.1678.1678

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

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detail.hit.zdb_id: 80069-7

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 7, No. sup2 ( 1992-01), p. 52-53

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.3109/10428199209058659

Language: English

Publisher: Informa UK Limited

Publication Date: 1992

detail.hit.zdb_id: 2030637-4

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4145-4145

Abstract: BACKGROUND: In chronic phase (CP) chronic myeloid leukemia (CML) nilotinib (NIL) showed better efficacy compared to imatinib. The higher rates of deep molecular response with NIL may translate into more patients (pts) eligible for treatment discontinuation. On the other hand, cardiovascular toxicity may limit NIL use in selected groups of pts (e.g. elderly pts). Long follow-up is required for a proper evaluation of the benefit-risk ratio between efficacy (including treatment-free remission [TFR] rates) and toxicity. However, only few data are currently available on the very long-term outcome of NIL treated pts. AIM: To describe the very-long term outcome of patients treated with nilotinib first-line. METHODS: The GIMEMA CML WP initiated in 2007 a phase II study (NCT 00481052) with NIL first-line (400 mg BID). Seventy-three adult (≥18 years old) pts with newly diagnosed, CP-CML were enrolled at 18 GIMEMA Centers in Italy. Median age was 51 (18-83) years. ELTS risk score was low in 64.4% of pts, intermediate in 30.1% of pts, and high in 5.5% of pts. Early and mid-term results have been previously published. Here, we report the very long-term outcome of this study, focusing on survival measures, TFR rates and adverse events. The updated, final results (with 10-year follow-up) of the trial will be available for presentation at the meeting. RESULTS: After a median follow-up of 92 months, 70 (95.9%) pts are alive and progression-free. Three pts (4.1%) died (progression to blast phase, n=1; CML-unrelated death, n=2). Failures according to ELN 2013 recommendation occurred in 5 (6.8%) pts (progression to BP, n=1; BCR-ABL transcript level 〉 1% at 12 months, n=2; confirmed loss of major molecular response, n=2). At last contact, 45 (61.6%) pts were still on NIL (dose ≥ 600 mg/day in 29 pts; 400 or 450 mg/day in 12 pts; ≤ 300 mg in 4 pts). Reasons for permanent NIL discontinuation in the remaining 28 (38.4%) pts were: adverse events (n=17, 23.3%; two of these pts maintained a deep molecular response without treatment - TFR); successful TFR attempts (n=9, 12.3%); failures (n=2 pts, 2.7%). The median age at CML diagnosis of pts obtaining the TFR was 47 (21-70) years. Fifteen athero-thrombotic events (ATEs) occurred in 13 (17.8%) pts (peripheral arterial occlusive disease, n=5; acute myocardial infarction, n=5; others ATEs, n=5), after a total NIL exposure of 478 years (3.1 events/100 pt-years). The median age at CML diagnosis of these pts was 66 (43 - 83) years; 8/13 (61.5%) pts had at least a baseline cardiovascular risk factor (hypertension, diabetes, hypercholesterolemia, or BMI ≥ 30). SUMMARY: These data highlight the efficacy of first-line NIL in the long-term, with excellent overall survival. TFR was obtained in 15% of pts, and particularly in younger ones. Some safety concerns remain, with ATEs occurring in 17.8% of pts (mainly in elderly ones), although none of these events was fatal. Disclosures Gugliotta: Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Castagnetti:Incyte: Honoraria; Pfizer: Honoraria; Bristol Myers Squiib: Consultancy, Honoraria; Novartis: Honoraria. Breccia:Novartis: Honoraria; Incyte: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Celgene: Honoraria. Levato:BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Stagno:Pfizer: Honoraria; Novartis: Honoraria; BMS: Honoraria; Incyte: Honoraria. Tiribelli:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Bocchia:Incyte: Honoraria; BMS: Honoraria; Novartis: Honoraria. Cavazzini:Novartis: Honoraria; Incyte: Honoraria; Pfize: Honoraria. Caocci:Novartis: Honoraria; Celgene: Honoraria. Albano:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Martinelli:Ariad: Consultancy, Other: trial grant; Amgen: Consultancy, Other: trial grant; Novartis: Consultancy, Other: trial grant; Pfizer: Consultancy, Other: trial grant; Janssen: Consultancy, Other: trial grant; Abbvie: Consultancy, Honoraria, Other: trial grant; Incyte: Consultancy, Other: trial grant; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: trial grant; Roche: Consultancy, Other: trial grant. Soverini:Incyte: Consultancy. Foà:Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pane:GSK: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: research founding; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Cavo:amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Saglio:Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; Jansen: Consultancy. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy. Rosti:BMS: Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-126163

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 5 ( 2000-11), p. 813-817

Abstract: Abstract —The purpose of this research was to obtain further information about the role of polymorphonuclear leukocytes in essential hypertension. These cells could be involved in the pathogenesis of organ injury. Thirty subjects (14 men and 16 women) with essential hypertension were enrolled. In these subjects we determined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate and N -formyl-methionyl-leucyl-phenylalanine, the polymorphonuclear leukocyte membrane fluidity, obtained by labeling the cells with 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene, cytosolic Ca 2+ concentration, obtained by marking the cells with Fura 2-AM, and integrin pattern (CD11a, CD11b, CD11c, and CD18), by using the indirect immunofluorescence with a flow cytometer. At baseline there was no difference in membrane fluidity between normal subjects and hypertensives, whereas hypertensives showed an increase in cytosolic Ca 2+ content and an increase of the phenotypical expression of CD11a, CD11b, and CD18. In normal subjects and in hypertensives, after activation, no variation was found in membrane fluidity and cytosolic Ca 2+ content. In normal subjects, after activation, we observed a significant increase of the expression of all adhesion molecules, whereas in hypertensives we found an increase of the expression of CD11b, CD11c, and CD18 but also a decrease of CD11a. The behavior of the polymorphonuclear leukocyte integrin profile may have several explanations, and in particular, the trend of CD11a after chemotactic activation may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance hypothetically present in this clinical condition.

Type of Medium: Online Resource

ISSN: 0194-911X , 1524-4563

URL: Article

DOI: 10.1161/01.HYP.36.5.813

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2000

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