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PubMed Journals Articles About "Alternative Dosing Strategy Of Ruxolitinib In Patients With Myelofibrosis" RSS

15:29 EST 18th January 2019 | BioPortfolio

Alternative Dosing Strategy Of Ruxolitinib In Patients With Myelofibrosis PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Alternative Dosing Strategy Of Ruxolitinib In Patients With Myelofibrosis articles that have been published worldwide.

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Showing "Alternative Dosing Strategy Ruxolitinib Patients With Myelofibrosis" PubMed Articles 1–25 of 42,000+

Ruxolitinib Therapy Followed by Reduced Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis - Myeloproliferative Disorders Research Consortium 114 study.

We evaluated the feasibility of ruxolitinib therapy followed by a reduced intensity conditioning (RIC) regimen for myelofibrosis (MF) patients undergoing transplant in a two stage Simon phase II trial. The aims were to decrease the incidence of graft failure (GF) and non-relapse mortality (NRM) in comparison to previous Myeloproliferative Disorders Research consortium 101 study. The plan was to enrol 11 patients each in related donor (RD), and unrelated donor (URD) arms, with trial termination if ≥3 failu...


Durability of spleen response affects the outcome of ruxolitinib-treated patients with myelofibrosis: Results from a multicentre study on 284 patients.

An Alternative Intermittent Eltrombopag Dosing Protocol for Treatment of Chronic Immune Thrombocytopenia.

Eltrombopag, an oral thrombopoietin receptor agonist, is dosed daily to treat chronic immune thrombocytopenia (ITP). Because it has a half-life of 26-35 hours in ITP patients and strict dietary restrictions that may impair quality of life and reduce compliance, we developed an alternative intermittent (AI) eltrombopag dosing protocol for ITP with dosing less frequently than once daily. Ten patients were treated with AI dosing for a median of 94 (range: 29-156) weeks, with most patients treated with 2-4 week...


IL-6 stimulation of DNA replication is JAK1/2 mediated in cross-talk with hyperactivated ERK1/2 signaling.

Myeloproliferative neoplasms (MPNs) are developing resistance to therapy by JAK1/2 inhibitor ruxolitinib. To explore the mechanism of ruxolitinib's limited effect, we examined the JAK1/2 mediated induction of proliferation related ERK1/2 and AKT signaling by proinflammatory interleukin-6 (IL-6) in MPN granulocytes and JAK2V617F mutated human erythroleukemia (HEL) cells. We found that JAK1/2 or JAK2 inhibition prevented the IL-6 activation of STAT3 and AKT pathways in polycythemia vera and HEL cells. Further...

Ruxolitinib treatment for steroid refractory acute and chronic graft versus host disease in children: Clinical and immunological results.

Ruxolitinib is a promising treatment for steroid refractory graft-versus-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate in acute GvHD and...

A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease.

Preclinical evidence indicates that the bone marrow microenvironment provides a protective niche for leukemic stem cells, allowing them to evade the effects of BCR-ABL tyrosine kinase inhibitors (TKIs), but that targeting of the JAK-STAT pathway with the JAK2 inhibitor ruxolitinib increases TKI-induced apoptosis. A phase I clinical trial (NCT01702064) investigated the tolerability and safety of treating chronic-phase chronic myeloid leukemia patients with ruxolitinib in combination with the BCR-ABL TKI nilo...

Genotype-guided dosing versus conventional dosing of warfarin: A meta-analysis of 15 randomized controlled trials.

Genotype-guided warfarin dosing algorithm is designed to predict the initial and stable dose of warfarin. However, whether this strategy is superior to conventional dosing method has not been consistently proven. To determine the benefit of genotype-guided dosing vs conventional dosing of warfarin, we performed a meta-analysis.

Patient Perspectives Regarding Allogeneic Bone Marrow Transplant in Myelofibrosis.

Hematopoietic stem cell transplant (HCT) is a curative treatment for patients with myelofibrosis (MF), however many eligible patients decline this potentially life-saving procedure. The reasons behind this decision are not clear. We sought to survey patients with MF to understand their perspective on HCT.

Evaluation of a Test Dose Strategy for Pharmacokinetically-guided Busulfan Dosing for Hematopoietic Stem Cell Transplant.

Targeted busulfan dosing helps to limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplant (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy utilizing a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (> 9 mg/kg) conditioning from January 2014 through October 2015. A weight-based test dose of 0.8 mg/kg was...

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients.

Data from previous reports, addressing the significance of genotype-guided dosing of warfarin in Egyptian patients, are infrequent and controversial. This study is aimed at demonstrating the validity of genetic dosing algorithms in Egyptian patients on warfarin therapy.

Captopril mitigates splenomegaly and myelofibrosis in the Gata1 murine model of myelofibrosis.

Allogeneic stem cell transplantation is currently the only curative therapy for primary myelofibrosis (MF), while the JAK2 inhibitor, ruxolitinib. Has been approved only for palliation. Other therapies are desperately needed to reverse life-threatening MF. However, the cell(s) and cytokine(s) that promote MF remain unclear. Several reports have demonstrated that captopril, an inhibitor of angiotensin-converting enzyme that blocks the production of angiotensin II (Ang II), mitigates fibrosis in heart, lung, ...

Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold ...

Treating early-stage myelofibrosis.

Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm associated with bone marrow fibrosis, splenomegaly, a high symptom burden, and poor prognosis. Treatment is based on a risk-adapted approach, with treatment guidelines generally recommending allogeneic stem cell transplant or drug-based therapy for patients with higher-risk or more advanced disease and recommending observation or the "watch-and-wait" strategy for those with lower-risk or early-stage MF. With the advent of t...

Thrombin Generation Testing in Patients with Myelofibrosis.

Primary myelofibrosis (PMF) is a chronic clonal myeloid disorder. Together with essential thrombocythemia (ET) and polycythemia vera (PV), it belongs to a group of Philadelphia chromosome-negative myeloproliferative neoplasms. Thrombotic events are serious complications negatively influencing the quality and length of these patients' lives. The confirmed risk factors for venous thromboembolism are age over 60 years, a positive history of thromboembolism, presence of common cardiovascular risks, JAK2 V617F m...

A National Survey of Valganciclovir Dosing Strategies in Pediatric Organ Transplant Recipients.

Data remain limited on the most appropriate valganciclovir (VGCV) dosing strategy for cytomegalovirus (CMV) prophylaxis and treatment in pediatric organ transplant recipients. Therefore, the objective of this study was to describe methods used to calculate VGCV dosing among pediatric transplant centers.

Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic Trough Concentrations in Critically Ill Patients.

Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three-hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from Fe...

WT1 gene is overexpressed in myeloproliferative neoplasms, especially in myelofibrosis.

Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexp...

What is pre-fibrotic myelofibrosis and how should it be managed in 2018?

The 2016 World Health Organization (WHO) classification for myeloproliferative neoplasms (MPN) divided myelofibrosis (MF) into pre-fibrotic (pre-MF) and overt-MF categories. This new classification, particularly the entity pre-MF, has been a subject of discussion between experts. Important questions have been raised in recent years, such as the need for bone marrow trephine for diagnosis; how this is interpreted and the weighting given to it in assigning a diagnosis; determination of prognosis for pre-MF pa...

Mechanisms for mTORC1 activation and synergistic induction of apoptosis by ruxolitinib and BH3 mimetics or autophagy inhibitors in JAK2-V617F-expressing leukemic cells including newly established PVTL-2.

The activated JAK2-V617F mutant is very frequently found in myeloproliferative neoplasms (MPNs), and its inhibitor ruxolitinib has been in clinical use, albeit with limited efficacies. Here, we examine the signaling mechanisms from JAK2-V617F and responses to ruxolitinib in JAK2-V617F-positive leukemic cell lines, including PVTL-2, newly established from a patient with post-MPN secondary acute myeloid leukemia, and the widely used model cell line HEL. We have found that ruxolitinib downregulated the mTORC1/...

Distinguishing autoimmune myelofibrosis from primary myelofibrosis.

Bone marrow fibrosis (BMF) is a histologic finding in a wide range of diseases, including malignancies, endocrine disorders, autoimmune diseases, and infections. Autoimmune myelofibrosis (AIMF) is an uncommon etiology of BMF; it can be secondary to a defined autoimmune disease, or it can be primary in the absence of a clinically diagnosed autoimmune disease but the presence of serologic evidence of autoantibodies. Distinguishing between primary myelofibrosis (PMF) and non-neoplastic AIMF is of the utmost im...

Anticoagulation at the extremes of body weight: choices and dosing.

The landscape of therapeutic anticoagulation has changed dramatically over the past decade, with availability of direct oral anticoagulants (DOACs), which inhibit factor Xa or thrombin. However, the optimal anticoagulant agent and dosing strategy for patients at both extremes of body weight has not been established for any anticoagulant, including DOACs, vitamin K antagonists (VKA) and the various heparin options. Areas covered: This paper reviews available evidence to assist clinicians in prescribing of an...

Genotype-guided Warfarin Dosing in Patients with Mechanical Valves: a Randomized Controlled Trial.

The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians.

Use of dermal gel pads in preventing and managing pressure ulcers in ICU: an audit.

Most of the pressure ulcers (PUs) that developed in the intensive care unit (ICU) of an acute trust were medical-device related. While use of a dermal pad was recommended as part of its pressure ulcer prevention strategy, staff were concerned that it tended to tear or split while in use. An alternative gel pad (Dermisplus® Prevent, Frontier Medical), that was cost-effective and appeared to be more robust, was identified. A 4-week non-comparative audit involving 37 patients was therefore undertaken to inves...

Pharmacokinetic and clinical outcomes when ideal body weight is used to dose busulfan in obese hematopoietic stem cell transplant recipients.

Weight-based dosing of intravenous busulfan is widely used in hematopoietic cell transplantation. However, a variety of dosing weights have been described. The objective of this retrospective study was to determine the pharmacokinetic impact of using ideal body weight as the initial dosing weight in obese as compared to non-obese transplant recipients. The secondary objectives were to describe the use of alternative dosing weights, the impact on survival, and the rates of toxicities. The mean steady-state c...

Intraoral granulocytic sarcoma as a manifestation of myelofibrosis: A case report and review of the literature.

Granulocytic sarcoma (GS) is an extramedullary tumor associated with myelodysplastic syndromes or myeloproliferative diseases. Intraoral manifestations are considered uncommon, with a reasonable number of cases, and are mostly related to leukemia. The association of oral GS and myelofibrosis is very rare and only three cases have been published. In this paper, we report the fourth case of oral lesion in a patient with a diagnosis of myelofibrosis. The aim of this study was to present a review of the literat...


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