- Zytokinsturm bei COVID-19 : Marburger Hochschulmedizin macht gute Erfahrungen mit Ruxolitinib
Die Überreaktion des körpereigenen Immunsystems in Form eines Zytokinsturms ist eine gefürchtete Komplikation bei schweren Infektionen mit dem neuartigen Coronavirus. Sie führt im schlimmsten Fall zum multiplen Organversagen. Als Gegenmittel werden verschiedene Immunmodulatoren klinisch getestet. Mediziner aus Marburg berichten über gute Erfahrungen mit dem JAK-Inhibitor Ruxolitinib.
- The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns - ScienceDirect
The survey focused on 3 aspects of PV care: diagnosis, treatment of erythrocytosis, and treatment of thrombocytosis. Given the level of experience among respondents, it is not surprising that utilization of the most informative tests (RCV, EPO level, ABG) in the diagnosis of PV was common. Somewhat surprising was the frequent use of less essential diagnostic studies, such as the LAP score, serum vitamin B12 level, bone marrow aspiration/biopsy, cytogenetics, abdominal CT scan, and chest x-ray. While the LAP score and serum vitamin B12 level were used in the PVSG studies as diagnostic criteria, their contemporary importance has lessened considerably (Table 7). Bone marrow aspiration/biopsy, cytogenetics, an abdominal CT scan, and a chest x-ray all can provide useful information in selected cases but probably are not necessary in the routine evaluation of a patient with suspected PV. Appropriately, only a small number of respondents used the CBC alone.
- The haematocrit and platelet target in polycythemia vera - Di Nisio - 2007 - British Journal of Haematology - Wiley Online Library
The PVSG‐01, the largest prospective PV cohort together with the ECLAP, included 431 patients (Berk et al, 1995). In the PVSG‐01, no haematologic parameter measured at the closest observation prior to the thrombotic event was associated with increased risk of thrombosis. In addition, patients of the PVSG protocol developed thrombotic complications when the haematocrit was reasonably well controlled by phlebotomy or myelosuppression.
- Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols - PubMed
The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment.
- The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera
Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% in females. Such targets lean on pathophysiological reasoning, while evidence from ECLAP and PVSG-01, the two largest prospective studies in this disease, suggests no difference in the rate of thrombosis in patients maintained at different HCT values below 50%–52%.
- Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera | NEJM
The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial.
- Chronische Entzündung: inflammatio – Labor, Diagnostik und Fortbildungen für Ärzte
Für den Nachweis der systemischen Entzündung stehen heute hochsensitiv messbare Zytokine zur Verfügung (TNF-α, IL-1, IL-6). Die gestörte Darmpermeabilität kann über das Zonulin im Serum oder auch alpha-1-Antitrypsin im Stuhl erfasst werden.
- Allele polycythemia - Search Results - PubMed
Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera enrolled in the RESPONSE study.
- Polycythemia and oxygen sensing - ScienceDirect
HIF-1 controls the expression of many genes including Epo. Identifying causal defects in other situations like post-renal transplant erythrocytosis and cases of autosomal dominant polycythemia with high Epo levels will help further understanding of the regulation of erythropoiesis.
- Recent insights regarding the molecular basis of myeloproliferative neoplasms
The discovery of the molecular features of MPN has revealed novel diagnostic and prognostic markers, provided insight into MPN pathobiology, and prompted new research questions. However, there is much that remain unknown. For example, although several heterogeneous noncanonical mutations in MPL and JAK2 have been identified [51,52], studies have not determined which mutations drive the disease in a significant proportion of triple-negative MPN cases. The hereditary basis of MPNs are poorly understood and future studies should seek to identify novel disease-related germline mutations. In addition, the functional disease outcomes of known germline mutations should be clearly defined.
- Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera - PubMed
We report here the first profound and sustained molecular responses with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response.
- Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development? - ScienceDirect
Recently chronic inflammation has been proposed as a trigger and driver of clonal evolution in MPNs. Herein, it is hypothesized that sustained inflammation may elicit the stem cell insult by inducing a state of chronic oxidative stress with elevated levels of reactive oxygen species (ROS) in the bone marrow, thereby creating a high-risk microenvironment for induction of mutations due to the persistent inflammation-induced oxidative damage to DNA in hematopoietic cells.
- The role of cytokines in the initiation and progression of myelofibrosis - ScienceDirect
The discovery of the Janus kinase 2 (JAK2) V617F mutation has led to the development of a number of JAK1/2 inhibitors in the treatment of MF and similar neoplasms. Here, the role of cytokines in MF initiation and progression is discussed, the impact of current therapies is reviewed, and new combination therapies are proposed, such as JAK1/2 inhibitors with interferons, statins, and epigenetic modifiers for patients with MF and related neoplasms.
- Perspectives on interferon-alpha in the treatment of polycythemia vera and related myeloproliferative neoplasms: minimal residual disease and cure?
In this review, we tell the IFN story in MPNs from the very beginning in the 1980s up to 2018 and describe the perspectives for IFN-alpha2 treatment of MPNs in the future. The mechanisms of actions are discussed and the impact of chronic inflammation as the driving force for clonal expansion and disease progression in MPNs is discussed in the context of combination therapies with potent anti-inflammatory agents, such as the JAK1–2 inhibitors (licensed only ruxolitinib) and statins as well. Interferon-alpha2 being the cornerstone treatment in MPNs and having the potential of inducing minimal residual disease (MRD) with normalization of the bone marrow and low-JAK2V617F allele burden, we believe that combination therapy with ruxolitinib may be even more efficacious and hopefully revert disease progression in many more patients to enter the path towards MRD.
- Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment - ScienceDirect
No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19–associated cytokine storm and reduce mortality.