- Are patients with high-risk polycythemia vera receiving cytoreductive medications? A retrospective analysis of real-world data. [Journal Article]
- EHExp Hematol Oncol 2018; 7:16
- CONCLUSIONS: Despite consistent guideline recommendations for cytoreductive therapy in patients with high-risk PV, this analysis revealed that only a minority of these patients received cytoreductive medication. A notable proportion of high-risk patients with PV would likely benefit from a revised treatment plan that aligns with current guidelines.
- [Myeloproliferative neoplasms: recent progresses in therapy]. [Journal Article]
- RKRinsho Ketsueki 2018; 59(6):741-746
- The expected survival duration of polycythemia vera (PV) and essential thrombocythemia (ET) patients is not substantially lower than that of the general population. The current goal of therapy is to ...
The expected survival duration of polycythemia vera (PV) and essential thrombocythemia (ET) patients is not substantially lower than that of the general population. The current goal of therapy is to prevent thrombohemorrhagic events associated with PV and ET. The current first line therapy for PV is phlebotomy, hydroxyurea (HU), and aspirin, while that for ET was HU or anagrelide. The follow-up phase 3 randomized trial wherein the hematological response was evaluated in PV patients treated with ropeginterferon alfa-2b, a next-generation monopegylated IFN-α-2b, or HU, demonstrated a superior hematological effect and a lower incidence of adverse events in patients who were treated with ropeginterferon. The prognosis of primary myelofibrosis (PMF) is poorer than that of PV or ET. The only curative therapeutic option for PMF patients is allogeneic hematopoietic stem cell transplantation (HSCT). Other than HSCT options, ruxolitinib ameliorates splenomegaly and MF-associated symptoms and provides an overall survival benefit in PMF patients with intermediate-2 or high risk. Several different JAK inhibitors have been developed; however, many of them were discontinued because of toxicity concerns. Recently, promising results have been demonstrated for the effect of different JAK inhibitors as well as the drugs that directly target anemia and bone marrow fibrosis.
- Anagrelide and the CALR mutation allele burden in essential thrombocythemia. [Journal Article]
- EOExp Oncol 2018; 40(2):152-153
- Successful replantation of 2 digits in a patient with thrombocytosis after splenectomy: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(22):e10951
- CONCLUSIONS: In patients with digital amputation, replantation can be attempted, even when thrombocytosis is expected, when requested by the patient. Furthermore, the platelet count should be actively controlled with medication to improve the survival rate of the reattached finger.
- Sustained Regression of Hydroxycarbamide Induced Actinic Keratoses after Switching to Anagrelide. [Journal Article]
- CRCase Rep Dermatol Med 2018; 2018:2874012
- Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatm...
Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatment with HC can result in the development of confluent actinic keratoses (AK) followed by invasive keratinocytic carcinomas ("squamous dysplasia"), preferentially on sun-exposed skin. Discontinuation or dose reduction of HC may result in partial improvement. A 59-year-old farmer after 14 years on HC (2 gr/d) and acetylsalicylic acid (100 mg/d) for ET, was referred for numerous, hyperkeratotic AK on face, scalp, and hands that could not be controlled with repeated (N = 15) cryosurgery sessions in the previous 3 years. Acitretin (0.32 mg/kg daily) and topical treatments (cryosurgery with ingenol mebutate) were initiated with only marginal improvement after 3 months. Acitretin dose was doubled and HC was switched to anagrelide (0.5 mg twice daily). Within a month the AK load regressed significantly and, at 3 months follow-up, complete clinical remission was achieved and acitretin was discontinued. Twenty months later the patient is clear from AK. In conclusion, the impressive and sustainable AK remission under anagrelide draws attention to a possible role of the phosphodiesterase 3 pathway, the major pharmacological target of anagrelide, as a potential therapeutic target for keratinocytic cancers.
- Skewed megakaryopoiesis in human induced pluripotent stem cell-derived haematopoietic progenitor cells harbouring calreticulin mutations. [Journal Article]
- BJBr J Haematol 2018; 181(6):791-802
- Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently b...
Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5-base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR-Ins5 mutation and from a healthy individual (WT). Megakaryopoiesis was more prominent in Ins5-haematopoietic progenitor cells (Ins5-HPCs) than in WT-HPCs, implying that the system recapitulates megakaryocytosis observed in the bone marrow of CALR-mutant ET patients. Ins5-HPCs exhibited elevated expression levels of GATA1 and GATA2, suggesting a premature commitment to megakaryocytic differentiation in progenitor cells. We also demonstrated that 3-hydroxy anagrelide markedly perturbed megakaryopoiesis, but not erythropoiesis. Collectively, we established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients harbouring CALR mutations and in detailed studies on mutant CALR in human haematological cell differentiation.
- Impact of white blood cells on thrombotic risk in patients with optimized platelet count in essential thrombocythemia. [Journal Article]
- EJEur J Haematol 2018 Mar 30
- 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.
- Ventricular tachyarrhythmia in a 78-year-old woman with essential thrombocythaemia. [Journal Article]
- BCBMJ Case Rep 2018 Feb 08; 2018
- Anagrelide is a phosphodiesterase-3 inhibitor used in the treatment of essential thrombocythaemia. Cardiovascular side effects such as ventricular tachycardia and cardiomyopathy are rare but potentia...
Anagrelide is a phosphodiesterase-3 inhibitor used in the treatment of essential thrombocythaemia. Cardiovascular side effects such as ventricular tachycardia and cardiomyopathy are rare but potentially fatal and should be made known to patients before starting the medication. It usually arises within the first 6 months after initiation of therapy and may be dose related. The elderly population are particularly susceptible. These cardiotoxicities result from an increase in cyclic AMP that induces positive inotropic and chronotropic effects and are often reversible with cessation of use. We report a case of a 78-year-old woman with essential thrombocythaemia and recently started on anagrelide who presented with syncope and multiple bruises and facial trauma and found to have developed ventricular tachyarrhythmia.
- Primary myelofibrosis and pregnancy outcomes after low molecular-weight heparin administration: A case report and literature review. [Case Reports]
- MMedicine (Baltimore) 2017; 96(46):e8735
- CONCLUSIONS: This case was rare and complex. Because it was related to pregnancy it required continuos collaboration and supervision between obstetrician and hematologist.
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- Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study. [Journal Article]
- HHaematologica 2018; 103(1):51-60
- Evaluation of Anagrelide (Xagrid®) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia pat...
Evaluation of Anagrelide (Xagrid®) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia patients treated with cytoreductive therapy. The primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid®) (n=804), other cytoreductive therapy (n=2666), or anagrelide + other cytoreductive therapy (n=141). The median age was 56 vs. 70 years for anagrelide vs. other cytoreductive therapy. Event rates (patients with events/100 patient-years) were 1.62 vs. 2.06 for total thrombosis and 0.15 vs. 0.53 for venous thrombosis. Anagrelide was more commonly associated with hemorrhage (0.89 vs. 0.43), especially with anti-aggregatory therapy (1.35 vs. 0.33) and myelofibrosis (1.04 vs. 0.30). Other cytoreductive therapies were more associated with acute leukemia (0.28 vs. 0.07) and other malignancies (1.29 vs. 0.44). Post hoc multivariate analyses identified increased risk for thrombosis with prior thrombohemorrhagic events, age ≥65, cardiovascular risk factors, or hypertension. Risk factors for transformation were prior thrombohemorrhagic events, age ≥65, time since diagnosis, and platelet count increase. Safety analysis reflected published data, and no new safety concerns for anagrelide were found. Live births occurred in 41/54 pregnancies (76%). clinicaltrials.gov Identifier: 00567502.