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Cancer Treatment Reviews Feb 2017Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to... (Meta-Analysis)
Meta-Analysis Review
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
Topics: Aged; Dose Fractionation, Radiation; Hematologic Neoplasms; Humans; Middle Aged; Patient Selection; Radiotherapy; Spleen; Splenomegaly; Treatment Outcome
PubMed: 28063304
DOI: 10.1016/j.ctrv.2016.11.016 -
Lupus Aug 2021Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with...
Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13-71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment.
Topics: Adolescent; Adult; Aged; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Cohort Studies; Female; Humans; Male; Middle Aged; Polycythemia Vera; Pregnancy; Recurrence; Thrombocytosis; Thrombosis; Young Adult
PubMed: 34192956
DOI: 10.1177/09612033211021154 -
Blood Advances Jun 2020Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer... (Meta-Analysis)
Meta-Analysis
Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.
Topics: Adult; Antineoplastic Agents; Dasatinib; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
PubMed: 32559295
DOI: 10.1182/bloodadvances.2019001329 -
American Journal of Hematology Jun 2014Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic)... (Meta-Analysis)
Meta-Analysis Review
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic) myelofibrosis (PMF). In this systematic review, we provide a comprehensive report on the incidence and prevalence of MPNs across the globe. Electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) were searched from their inception to August 2012 for articles reporting MPN incidence or prevalence rates. A random effects meta-analysis was undertaken to produce combined incidence rates for PV, ET, and PMF. Both heterogeneity and small study bias were assessed. Thirty-four studies were included. Reported annual incidence rates ranged from 0.01 to 2.61, 0.21 to 2.27, and 0.22 to 0.99 per 100,000 for PV, ET, and PMF, respectively. The combined annual incidence rates for PV, ET, and PMF were 0.84, 1.03, and 0.47 per 100,000. There was high heterogeneity across disease entities (I(2) 97.1-99.8%) and evidence of publication bias for ET and PMF (Egger test, P = 50.007 and P ≤ 0.001, respectively).The pooled incidence reflects the rarity of MPNs. The calculated pooled incidence rates do not reflect MPN incidence across the globe due to the high unexplained heterogeneity. Improved, widespread registration of MPNs would provide better information for global comparison of the incidence and prevalence of MPNs.
Topics: Humans; Incidence; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 24971434
DOI: 10.1002/ajh.23690 -
Cancer Control : Journal of the Moffitt... 2021Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated...
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the overproduction of mature myeloid cells and are often associated with an acquired genetic mutation of . Various epidemiological studies have indicated associations between environmental factors, lifestyle factors, and host characteristics with developing MPNs. This review aims to collect and summarize the existing information on these risk factors and establish their association with pathogenesis MPNs. Medline, Embase, PubMed, and grey literature were systematically searched using key terms for MPNs, and epidemiological study designs, that is, cross-sectional studies, case-control, and cohort, that investigated the risk factors for MPNs published were identified. Out of the 4621 articles identified, 20 met the selection criteria and were included in this review. Heterogeneity, study reliability, and bias were assessed. A significant association was found between smoking and the development of MPNs. This relationship has been explained by the substantial increase in several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments leading to the development of MPNs. Obesity was modestly linked with an increased risk of MPNs. The underlying mechanisms have been linked to changes in endocrine, metabolic, and inflammatory systems. No strong association was found between exposure to hazardous substances, that is, benzene and MPNs, but further investigation on the effects of increased levels and duration of exposure on hematopoietic stem cells will be beneficial. Unique individual and host variations have been determined as a modifier of disease pathogenesis and phenotype variations. There is a higher incidence rate of females developing MPNs, specifically ET, than males with higher PV incidence. Therefore, gender contributes to the heterogeneity in myeloproliferative neoplasm. Studies identified as part of this review are very diverse. Thus, further in-depth assessment to explore the role of these etiological factors associated with MPNs is warranted.
Topics: Cigarette Smoking; Environment; Environmental Exposure; Female; Humans; Inflammation Mediators; Life Style; Male; Myeloproliferative Disorders; Obesity; Oxidative Stress; Philadelphia Chromosome; Risk Factors; Sex Distribution; Sociodemographic Factors
PubMed: 34645293
DOI: 10.1177/10732748211046802 -
Annals of Medicine Dec 2023There is a lack of evidence regarding whether combination therapy of hypomethylating agents (HMAs) has better outcomes than HMA monotherapy in patients with Philadelphia... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of combination therapies vs monotherapy of hypomethylating agents in accelerated or blast phase of Philadelphia negative myeloproliferative neoplasms: a systematic review and meta-analysis.
BACKGROUND
There is a lack of evidence regarding whether combination therapy of hypomethylating agents (HMAs) has better outcomes than HMA monotherapy in patients with Philadelphia chromosome-negative accelerated or blast phase myeloproliferative neoplasms (MPN-AP/BP).
MATERIALS AND METHODS
Pubmed, Embase, Web of Science and Cochrane library databases were searched for studies from inception of each database until 31 December 2021. Data extraction and synthesis were conducted following the PRISMA reporting guideline.
RESULTS
It was found that HMAs plus venetoclax therapy yielded a higher CR/CRi rate than HMAs alone [36% vs 19%, = .0204] and a higher CR rate than HMAs plus ruxolitinib [22% vs 8%, = .0313]. HMAs plus ruxolitinib combination showed a higher ORR than HMA monotherapy [45% vs 30%, = .0395], but there was no improvement in CR/CRi. The one-year and two-year OS rate for patients treated with HMAs plus venetoclx/ruxolitinib demonstrated a trend towards prolonged survival than HMAs alone [HMAs plus venetoclax: 24% vs 11%, = .1295 and 12% vs 3%, = .2357; HMAs plus ruxolitinib: 25% vs 11%, = .0774 and 33% vs 3%, = .051].
CONCLUSION
It was confirmed that HMA in combination with venetoclax is an effective and well-tolerated option in MPN-AP/BP patients in pre- as well as post-haematopoietic stem cell transplantation settings. HMA plus ruxolitinib therapy was revealed to be effective in patients with MPN-AP.Key MessagesCombination therapy with HMAs and venetoclax/ruxolitinib was associated with improved outcomes than HMAs alone in MPN-AP/BP patients.Further large-scale randomized controlled trials are needed to confirm regarding to the optimal treatment for this patient population.
Topics: Humans; Treatment Outcome; Blast Crisis; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 36644935
DOI: 10.1080/07853890.2022.2164611 -
BMC Cancer Feb 2019Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN.
METHODS
Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation.
RESULTS
A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6-23.8%; I 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0-20.0%; I 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9-7.8%; I 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0-7.8%; I 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding.
CONCLUSIONS
Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding.
Topics: Hemorrhage; Humans; Myeloproliferative Disorders; Philadelphia Chromosome; Prevalence; Thrombosis
PubMed: 30819138
DOI: 10.1186/s12885-019-5387-9 -
Life (Basel, Switzerland) Jul 2021Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid... (Review)
Review
Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates ( = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts ( = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.
PubMed: 34357048
DOI: 10.3390/life11070677 -
Journal of Oncology Pharmacy Practice :... Sep 2022To provide up to date guidance, practice recommendations and highlight barriers to medication adherence in the long-term management of chronic myeloproliferative...
PURPOSE
To provide up to date guidance, practice recommendations and highlight barriers to medication adherence in the long-term management of chronic myeloproliferative neoplasms (MPNs).
AIM
Current drug therapy for MPN is not curative and has not been shown to prolong survival. The main indication for treatment is the prevention of thrombosis and medication adherence remains a challenge in this group of patients. Identifying potentially modifiable barriers to medication adherence including primary nonadherence and non-persistent adherence enables timely interventions to be put in place and improve overall medication adherence.
METHODS
A systematic review of peer-reviewed literature and expert opinions was performed using electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) that were searched for articles reporting MPN and medication adherence. Discussions A case vignette is discussed throughout the article and expert opinion with international peer reviewed guidelines that are authored to support clinical decision making at the point of care were utilised. The evidence base was combined with more practical/clinical (data based) insight from real world clinical practice. Adoption of a broad range of digital health care activities and services in the health care system (telehealth applications) by the advanced practice providers (Non-Medical Prescribers-NMPs) in MPN clinics included medication prescribing and management, oral drug compliance and adherence evaluations, interventions, chronic care management, counselling and patient education on treatments.
CONCLUSION
Current drug therapy for MPN is neither curative nor has it been shown to prolong survival, and medication adherence remains a challenge in this group of patients. The longevity of the patients' disease course may contribute to the high risk of non-adherence in this patient cohort. Poor adherence to long-term therapies severely compromises the effectiveness of treatment. Adherence interventions should be tailored to the needs of the patient in order to achieve maximum impact. Interventions aimed at improving adherence provide the best experience and outcome for the patient and their families and can have a profound impact on the quality of life and mitigation of disease consequences.
Topics: Humans; Medication Adherence; Myeloproliferative Disorders; Neoplasms; Quality of Life; Thrombosis
PubMed: 35296179
DOI: 10.1177/10781552221082293 -
Heart, Lung & Circulation Mar 2022Polycythaemia vera (PV) is a condition that may potentially put patients undergoing cardiac surgery at an increased risk of bleeding and thrombosis; however, there is... (Review)
Review
OBJECTIVES
Polycythaemia vera (PV) is a condition that may potentially put patients undergoing cardiac surgery at an increased risk of bleeding and thrombosis; however, there is currently a paucity of literature regarding the management of these patients. We aim to examine the literature in this systematic review to indicate the interventions that may be considered to minimise complications.
METHODS
We conducted a literature search using keywords and MeSH terms to identify articles discussing PV and cardiac surgery. The studies were identified and qualitatively analysed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol.
RESULTS
In total, 10 case reports representing 11 patients were identified for this systematic review and were included in qualitative analysis. 63.6% of patients had preoperative intermittent phlebotomy, and the majority of patients received postoperative therapy that involved one antiplatelet agent and one anticoagulant. Generous perioperative fluid management, phlebotomy, preservation of core body temperature, early extubation, monitoring of myocardial ischaemia, infarction and vascular events, intense chest physiotherapy and patient mobilisation are important to consider to reduce the risk of complications arising from surgery.
CONCLUSION
These considerations should be systematically discussed in a multidisciplinary team, where the acute surgical need can be balanced appropriately against the risk of haemorrhage and thrombosis.
Topics: Anticoagulants; Coronary Artery Bypass; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Thrombosis
PubMed: 34794873
DOI: 10.1016/j.hlc.2021.10.012