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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 -
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 -
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 -
Seminars in Thrombosis and Hemostasis Jul 2021Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic...
Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic review, we provide an overview and discussion of the current literature in regards to clinical manifestations, diagnosis, and treatment of altered fibrinolysis in patients suffering from hematological malignancies, beyond acute promyelocytic leukemia. We performed a systematic literature search employing the databases Pubmed, Embase, and Web of Science to identify original studies investigating fibrinolysis in hematological malignancies. Studies investigating fibrinolysis in acute promyelocytic leukemia or disseminated intravascular coagulation were excluded. We identified 32 studies fulfilling the inclusion criteria. A majority of the studies were published more than two decades ago, and none of the studies examined all available markers of fibrinolysis or used dynamic clot lysis assays. In acute leukemia L-asparaginase treatment induced a hypofibrinolytic state, and prior to chemotherapy there seemed to be little to no change in fibrinolysis. In studies examining fibrinolysis during chemotherapy results were ambiguous. Two studies examining multiple myeloma indicated hypofibrinolysis prior to chemotherapy, and in another plasma cell disease, amyloid light chain-amyloidosis, clear signs of hyperfibrinolysis were demonstrated. In myeloproliferative neoplasms, the studies reported signs of hypofibrinolysis, in line with the increased risk of thrombosis in this disease. Only one study regarding lymphoma was identified, which indicated no alterations in fibrinolysis. In conclusion, this systematic review demonstrated that only sparse, and mainly old, evidence exists on fibrinolysis in hematological malignancy. However, the published studies showed a tendency toward hypofibrinolysis in myeloproliferative disorders, an increased risk of hyperfibrinolysis, and bleeding in patients with AL-amyloidosis, whereas studies regarding acute leukemias were inconclusive except with regard to L-asparaginase treatment, which induced a hypofibrinolytic state.
Topics: Amyloidosis; Asparaginase; Blood Coagulation Disorders; Fibrinolysis; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis
PubMed: 34058766
DOI: 10.1055/s-0041-1725099 -
Expert Review of Hematology Jan 2020: Recent advances in the prognostic scheme and treatment of primary and secondary myelofibrosis (MF) have resulted in an overwhelming amount of clinical information to...
: Recent advances in the prognostic scheme and treatment of primary and secondary myelofibrosis (MF) have resulted in an overwhelming amount of clinical information to assimilate. The authors believe a comprehensive review that summarizes the most recent published literature, could serve as guidelines for the practicing hematologist.: The authors provide a summary of landmark articles regarding epidemiology, symptoms, and pathogenesis of disease. The authors conducted a systematic literature review to answer questions regarding differences between primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), appropriate use and selection of the current risk-stratification models, early versus late treatment of MF and current practices in allogeneic hematopoietic stem cell transplantation (allo-HCT) for MF. The authors conclude the article with their clinical opinion based on their experience and literature review. The purpose of this article is to identify current practices, address any variation, identify and investigate conflicting results and produce statements to guide decision-making.: In this section, the authors advocate for and provide examples of a standardized way of incorporating future discoveries in the pathogenesis and risk-stratification models of MF. They also discuss the importance of using only one risk-stratification model for PMF and one for SMF and their reasoning for early instead of late treatment of MF.
Topics: Allografts; Clinical Decision-Making; Hematopoietic Stem Cell Transplantation; Humans; Models, Biological; Practice Guidelines as Topic; Primary Myelofibrosis; Risk Assessment; Risk Factors
PubMed: 31709843
DOI: 10.1080/17474086.2020.1691519 -
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 -
Future Oncology (London, England) Jun 2023A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using different types of BCR-ABL inhibitors. Literature published between 2000 and April 2022 were searched using PubMed, Cochrane Library, Embase and ClinicalTrials.gov. A total of 12 studies were included for meta-analysis. The results showed that the incidence of all-grade or high-grade rash associated with new-generation BCR-ABL inhibitors had no significant difference compared with a standard dose of imatinib. Subgroup analysis suggested that, compared with imatinib, the incidence of all grades of rash was higher in the nilotinib, bosutinib and ponatinib groups. For CML patients treated with nilotinib, bosutinib and ponatinib, the occurrence of skin toxicity should not be ignored.
Topics: Humans; Imatinib Mesylate; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Exanthema; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 37368411
DOI: 10.2217/fon-2022-1008 -
Seminars in Thrombosis and Hemostasis Feb 2021Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by increased platelet counts. ET has an incidence of 0.6 to 2.5 per 100,000 per year in...
Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by increased platelet counts. ET has an incidence of 0.6 to 2.5 per 100,000 per year in Europe and North America. The disease is characterized by an increased thromboembolic risk, possibly caused by increased platelet counts. Furthermore, increased platelet function and/or increased platelet turnover may play a role. We aimed to explore: (1) whether platelet function and platelet turnover are increased in ET patients compared with healthy controls, and (2) whether these parameters are associated with increased thromboembolic risk and, therefore, may support decision-making on treatment in ET patients. We performed a systematic literature search on March 20, 2020 in Embase and PubMed following the Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) guidelines. In total, 1,923 articles were identified, 38 of which were included according to prespecified inclusion and exclusion criteria. Among the 38 studies, platelet activation (CD36 and CD62P) was investigated in 18 studies and was found to be increased in 12 of these. Platelet aggregation was investigated in 21 studies and was reported to be reduced in 20 of them. Platelet turnover (immature platelet count and mean platelet volume) was investigated in five studies with inconclusive results. No parameters were reported to predict the risk of thromboembolic events. In conclusion, platelet activation was increased in ET patients, but platelet aggregation was reduced. Future studies exploring markers of thromboembolic risk in ET patients are warranted.
Topics: Blood Platelets; Female; Humans; Platelet Function Tests; Thrombocythemia, Essential
PubMed: 33525042
DOI: 10.1055/s-0040-1718873 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2020Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow failure, increased risk of progression to acute myeloid leukemia, and constitutional symptoms. For over 3 decades, various formulations of interferon (IFN) have been used for the treatment of MF, with variable results, and the role of IFN in the treatment of MF is evolving.
PATIENTS AND METHODS
For this systematic review and meta-analysis, Medline and Embase via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were searched from inception through March 2019 for studies of pegylated IFN (peg-IFN) and non-peg-IFN in MF patients. The primary outcome of overall response rate was defined as a composite of complete response, partial response, complete hematologic response, and partial hematologic response. Random-effects models were used to pool overall response rate, and metaregression analyses were performed to compare peg-IFN and non--peg-IFN formulations.
RESULTS
Among the 10 studies with 141 MF patients included, the overall response rate was 49.9% (95% confidence interval [CI], 30.4-69.3), and there was no statistically significant difference (P = .99) between peg-IFN (50.0%; 95% CI, 26.2-73.9; I = 76.9%) and non-peg-IFN (49.6%; 95% CI, 20.5-79.0; I = 56.7%). Treatment discontinuation resulting from adverse events was common with non-peg-IFN at 35.8% (95% CI, 3.5-68.1) per year, and less in the one study on peg-IFN (0.5% per year).
CONCLUSION
IFN can lead to hematologic improvements in a subset of MF patients, but study quality is limited and heterogenous. Biomarkers predicting response to IFN and formulations with improved tolerability are needed.
Topics: Humans; Interferon-alpha; Primary Myelofibrosis
PubMed: 32669244
DOI: 10.1016/j.clml.2020.05.018 -
Blood Reviews Nov 2023Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation... (Review)
Review
Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.
Topics: Humans; Androgens; Primary Myelofibrosis; Retrospective Studies; Neoplasms; Anemia, Aplastic; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Myeloproliferative Disorders; Thrombocytopenia
PubMed: 37709654
DOI: 10.1016/j.blre.2023.101132