- Anagrelide is an anti-megakaryocytic and not an anti-platelet agent. [Journal Article]
- PPlatelets 2018 Nov 07; :1-2
- Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study. [Journal Article]
- LRLeuk Res 2018; 74:105-109
- EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates...
EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644).
- Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide. [Journal Article]
- AJAm J Hematol 2018 Sep 25
- First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice includ...
First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1-1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.
- Synthesis and characterization of metals-substituted cobalt ferrite [Mx Co(1-x) Fe2O4; (M = Zn, Cu and Mn; x = 0 and 0.5)] nanoparticles as antimicrobial agents and sensors for Anagrelide determination in biological samples. [Journal Article]
- MSMater Sci Eng C Mater Biol Appl 2018 Nov 01; 92:644-656
- Nanocrystalline spinel ferrite nanoparticles [MxCo(1-x)Fe2O4;(M = Zn,Cu,Mn;x = 0 and 0.5)] like: Cobalt ferrite (CFO), Zinc Cobalt ferrite (ZCFO), Copper Cobalt ferrite (CCFO), and Manganese Cobalt f...
Nanocrystalline spinel ferrite nanoparticles [MxCo(1-x)Fe2O4;(M = Zn,Cu,Mn;x = 0 and 0.5)] like: Cobalt ferrite (CFO), Zinc Cobalt ferrite (ZCFO), Copper Cobalt ferrite (CCFO), and Manganese Cobalt ferrite (MCFO) modified carbon paste electrodes (CPE) were synthesized via sol-gel technique utilizing citric acid and ethylene glycol as a polymerization agent. The synthesized ferrite NPs were used as bi-functional smart biosensor, not only used to determine the drug Anagrelide-HCl (ANDH) in urine and serum samples, but also possesses antimicrobial potential against some pathogenic microbes, founded in the biological samples. The synthesized ferrite NPs were confirmed by XRD, FTIR spectroscopy, SEM, EDX, and elemental mapping images. Antimicrobial activities of ferrite NPs against selected urinary tract infected microbes were investigated. From XRD data and FTIR spectroscopy it is found that the average crystallite size is lies in the range 12.86 to 33.92 ± 1.5 nm, also the bond lengths RA and RB increase from 1.8986 to 1.9145 Å and from 2.0434 to 2.0606 Å respectively and Debye temperature θD lies in the range of 681.52-708.87 K. Our study describes the improvement of a screen-printed sensor, modified with ferrite NPs materials for rapid, sensitive and cost-effective quantification of ANDH present in the real samples such as blood serum samples, urine and in the pharmaceutical formulations. The results obtained postulate a linear regression between the ANDH charge density of peak current and its concentration in the range from (0.64-8.18 μg/ml) with DL 0.31 μg/ml and QL 0.94 μg/ml. Antimicrobial results indicated that ZCFO NPs were a novel antibacterial agent against Klebsiella pneumoniae (28.0 mm ZOI), and multidrug-resistant bacteria Enterococcus faecalis (27.0 mm ZOI). Additionally, ZCFO NPs were active against Candida albicans (18.0 mm ZOI) seems to be a smart antifungal agent. Therefore, ZCFO NPs can be used as applicant resources for industrial, medical, and biological applications.
- A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia. [Clinical Trial, Phase III]
- IJInt J Hematol 2018; 108(5):491-498
- Cytoreductive therapy is used in high-risk essential thrombocythemia (ET) to reduce risk of thrombohemorrhagic complications. Anagrelide is an orally active, quinazolone-derived platelet-lowering age...
Cytoreductive therapy is used in high-risk essential thrombocythemia (ET) to reduce risk of thrombohemorrhagic complications. Anagrelide is an orally active, quinazolone-derived platelet-lowering agent approved for first-line treatment of high-risk ET in Japan. Long-term safety and efficacy data were collected from 53 Japanese high-risk ET patients (Study 308); 41 patients who completed Study 308 entered this phase 3b, open-label extension (Study 309; NCT01467661). Reductions in mean platelet counts occurred throughout the study, from 1021.6 × 109/L (at Study 308 baseline) to 675.4 × 109/L at final assessment. At month 48 (since Study 308 enrollment), mean platelet count was 444.5 × 109/L in the 10 patients who completed 4 years of therapy. Overall, platelet counts decreased from 1088.3 × 109/L at Study 308 baseline (n = 33) to 473.5 × 109/L at final assessment (n = 31). Long-term platelet count reductions were maintained without marked changes in mean anagrelide dose. Anagrelide was generally well tolerated, with anemia (54.7%) and headache (49.1%) as the most frequent adverse events. These findings indicate that anagrelide effectively reduces platelet counts in high-risk Japanese ET patients, with titration resulting in a well-tolerated, effective and sustainable dose. In conclusion, these results support anagrelide administration to high-risk Japanese ET patients using individualized dosing strategies defined in instructions previously approved in Europe and the USA.
- 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.
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- 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.