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Clinical and Applied... 2023Thrombotic events are the most frequent manifestations of essential thrombocythemia (ET). The objective of this study is to determine the incidence of thrombosis at... (Meta-Analysis)
Meta-Analysis
Thrombotic events are the most frequent manifestations of essential thrombocythemia (ET). The objective of this study is to determine the incidence of thrombosis at different sites on follow-up in patients with ET. We searched PubMed, Web of Science, and The Cochrane Library databases and calculated the incidence of thrombosis by pooling and analyzing the extracted data using a random-effects model. A total of 70 studies (N = 25,805) were included in the analysis. The total and annual incidences of arterial thrombosis on follow-up were 13.4% and 2.0%, respectively. The total and annual incidences of the different manifestations of arterial thrombosis were as follows: stroke (5.3% and 0.8%), transient ischemic attack (5.1% and 1.2%), myocardial infarction (2.4% and 0.5%), unstable angina (0.9% and 0.2%), and peripheral arterial thrombosis (2.0% and 0.2%), respectively. In contrast, the total and annual incidences of arterial thrombosis in JAK2-positive patients were 18.4% and 2.7%, respectively. The total and annual incidences of arterial thrombosis in JAK2-negative patients were 5.9% and 0.8%, respectively. The total and annual incidences of venous thrombosis were 5.5% and 0.7%, respectively, and the incidences of the different manifestations of venous thrombosis at different sites were as follows: peripheral venous thrombosis (2.9% and 0.5%), superficial venous thrombosis (1.8% and 0.7%), deep venous thrombosis (1.6% and 0.3%), abdominal venous thrombosis (0.8% and 0.1%), pulmonary embolism (0.3% and 0.1%), and cerebral venous thrombosis (0.2% and 0%), respectively. The total and annual incidences of venous thrombosis in JAK2-positive patients were 7.4% and 1.2%, respectively. The total and annual incidences of venous thrombosis in JAK2-negative patients were 1.6% and 0.4%, respectively. The incidence of arterial thrombosis was higher than that of venous thrombosis in patients with ET. Arterial thrombosis manifested with cerebral arterial thrombosis, followed by cardiac thrombosis. Venous thrombosis events were mainly peripheral and superficial venous thrombosis. JAK2-positive patients have a higher incidence of arterial and venous thromboses than JAK2-negative patients, the sequence of thrombsis sites was similar to that of the overall patients.
Topics: Humans; Thrombocythemia, Essential; Incidence; Follow-Up Studies; Thrombosis; Venous Thrombosis; Risk Factors
PubMed: 37350087
DOI: 10.1177/10760296231181117 -
Future Oncology (London, England) Mar 2023Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312... (Meta-Analysis)
Meta-Analysis Review
Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312 patients from 24 retrospective studies. The complete remission (CR) rate of acute lymphoblastic leukemia-like induction chemotherapy was 82%, and the overall survival (OS) was 15.75 months; the CR rate of acute myeloid leukemia-like chemotherapy was 51%, and the OS was 7.18 months; and the CR rate of cyclophosphamide, doxorubicin, vincristine and prednisone-like chemotherapy was 50%, and the OS was 12.06 months. Acute lymphoblastic leukemia-like induction chemotherapy has the best CR rate and OS.
Topics: Humans; Induction Chemotherapy; Retrospective Studies; Hematologic Neoplasms; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myeloproliferative Disorders; Dendritic Cells
PubMed: 36919853
DOI: 10.2217/fon-2022-0521 -
Leukemia & Lymphoma Sep 2023Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis,...
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML's clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.
Topics: Humans; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Mutation; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Prognosis; Receptors, Colony-Stimulating Factor
PubMed: 37395413
DOI: 10.1080/10428194.2023.2227750 -
Expert Review of Hematology Feb 2023Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have...
INTRODUCTION
Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have been used mostly. Recently, direct oral anticoagulants (DOACs) are used in venous thromboembolism (VTE) and cancer-associated thrombosis (CAT). With the adoption of data from CAT and VTE, the usage of DOACs in MPNs is increasing.
AREAS COVERED
In this paper, we performed a systematic review to the current literature regarding the usage of DOACs in MPNs. Eleven studies involving 944 patients were included. The reasons for initiating DOACs were secondary prophylaxis for thrombosis (arterial or venous) and atrial fibrillation (AF) in 562 and 382 patients, respectively. A total of 84 (8.9%) recurrent thrombotic (arterial or venous) events recorded. Forty-six (8.1%) events occurred in the thrombosis group (arterial or venous) and 38 (9.9%) events occurred in patients with AF.
EXPERT OPINION
Ease of management and patient comfort should be regarded as benefits of DOACs compared to VKAs. However, it would be appropriate to bring an individualized approach until we obtain high-quality data with prospectively designed studies involving more patients and longer follow-up time concerning the use of DOACs in patients with MPNs.
Topics: Humans; Venous Thromboembolism; Anticoagulants; Myeloproliferative Disorders; Thrombosis; Atrial Fibrillation; Neoplasms; Administration, Oral; Vitamin K
PubMed: 36709432
DOI: 10.1080/17474086.2023.2174515 -
Journal of Comparative Effectiveness... Jun 2022To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid... (Review)
Review
To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid leukemia (CML). We identified 155 references in Chinese- and English-language journals from 2001 to 2021. The age-adjusted mortality rate in Chinese CML patients was decreasing. Imatinib treatment had a higher annual treatment failure risk than nilotinib (0.199 vs 0.041). Patients with TKI treatment failure tended to be young (median: 38.6 years), have progressive disease (44.3%) and harbor mutations (51.6%). The disease burden of TKI treatment failure included reduced health outcomes and increased health resource utilization and costs. CML relapse cases could continuously rise in China due to increasing TKI treatment failure over extended survival.
Topics: Asian People; Humans; Imatinib Mesylate; Language; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors
PubMed: 35411807
DOI: 10.2217/cer-2022-0032 -
Expert Opinion on Drug Safety Jan 2024Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of different doses of ponatinib versus other tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia: a systematic review and network meta-analysis.
OBJECTIVE
Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this study was to understand the efficacy and safety of different doses of ponatinib in the treatment of CML, and to compare it with other tyrosine kinase inhibitors (TKIs).
METHOD
A network meta-analysis (NMA) was conducted by searching randomized controlled trials (RCTs) of ponatinib in patients with CML to compare the efficacy and safety of ponatinib, and ranked under the cumulative ranking curve (SUCRA) to evaluate the optimal treatment.
RESULTS
A total of seven articles with eight RCTs were included in this study, involving 45 mg, 30 mg and 15 mg ponatinib doses. Seven outcome indexes were analyzed. The results showed that 45 mg ponatinib was superior to other doses of ponatinib and other TKIs in CCyR, MCyR and CHR, but the incidence of SAEs and AOEs was significantly higher than other treatment regimens.
CONCLUSION
Ponatinib, with an initial dosage of 45 mg and a gradual reduction to 15 mg, may be a more favorable option for patients with CML at all stages of disease progression, rather than just those in the chronic phase of CML.
Topics: Humans; Tyrosine Kinase Inhibitors; Network Meta-Analysis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Pyridazines; Protein Kinase Inhibitors; Antineoplastic Agents; Imidazoles
PubMed: 37852954
DOI: 10.1080/14740338.2023.2273339 -
International Journal of Molecular... Feb 2023Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML)... (Meta-Analysis)
Meta-Analysis
Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in (rs1045642, rs2032582, rs1128503) and one in (rs2231142) and the imatinib plasma trough concentration (C) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the c.421 A allele showed higher imatinib plasma C with respect to the CC/CA carriers (C, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between polymorphisms and imatinib C, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between c.421C>A and imatinib plasma C in GIST and CML patients.
Topics: Humans; Adenosine Triphosphate; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Gastrointestinal Stromal Tumors; Genotype; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prospective Studies
PubMed: 36834713
DOI: 10.3390/ijms24043303 -
JAMA Network Open Oct 2019Myeloproliferative neoplasms (MPNs) are increasingly being identified in women of childbearing potential. Pregnancy in women with MPNs is associated with maternal... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Myeloproliferative neoplasms (MPNs) are increasingly being identified in women of childbearing potential. Pregnancy in women with MPNs is associated with maternal thrombosis, hemorrhage, and placental dysfunction leading to fetal growth restriction or loss.
OBJECTIVE
To evaluate the association between the use of aspirin, heparin, interferon, or combinations and live birth rate and adverse maternal outcomes in pregnant women with MPNs.
DATA SOURCES
Systematic searches of MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and the MEDLINE Epub Ahead of Print and In-Process and Other Non-Indexed Citations from inception to July 19, 2018, with no language restrictions, was conducted. Key search terms included myeloproliferative disorders, polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
STUDY SELECTION
A study was eligible if it included pregnant patients with MPNs; interventions included aspirin, heparin, and/or interferon; there was a comparison group in which patients did not receive the intervention; the study reported on at least 1 of the study outcomes; and it was a randomized, case-control, or cohort study or series of at least 10 pregnancies. Data were extracted in duplicate; 0.5% of identified studies met selection criteria.
DATA EXTRACTION AND SYNTHESIS
The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and reported in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using the Mantel-Haenszel approach.
MAIN OUTCOMES AND MEASURES
Outcomes were the number of live births and maternal complications, specifically, arterial or venous thrombosis, hemorrhage, and preeclampsia.
RESULTS
Twenty-two studies reporting on 1210 pregnancies were included. The live birth rate was 71.3% (95% CI, 65.1%-77.6%). Use of aspirin (11 studies, 227 patients; unadjusted odds ratio, 8.6; 95% CI, 4.0-18.1) and interferon (6 studies, 90 patients; unadjusted odds ratio, 9.7; 95% CI, 2.3-41.0) were associated with higher odds of live birth. Addition of heparin to aspirin was not associated with higher odds of live birth (6 studies, 96 patients; unadjusted odds ratio, 2.1; 95% CI, 0.5-9.0). The most common adverse maternal event was preeclampsia, with an incidence of 3.1% (95% CI, 1.7%-4.5%).
CONCLUSIONS AND RELEVANCE
Most studies reported on pregnancy with essential thrombocythemia. Few studies reported on pregnancy with polycythemia vera and none with myelofibrosis met the inclusion criteria. Most studies were retrospective and early pregnancy losses may have been underreported. Moderate-quality evidence suggests that aspirin or interferon is associated with higher odds of live birth in pregnant women with MPN.
Topics: Antineoplastic Agents; Aspirin; Birth Rate; Female; Fibrinolytic Agents; Heparin; Humans; Interferons; Live Birth; Myeloproliferative Disorders; Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 31584685
DOI: 10.1001/jamanetworkopen.2019.12666 -
Hematology (Amsterdam, Netherlands) Dec 2021Infections in ruxolitinib-treated myeloproliferative neoplasm (MPN) patients were reported frequently. This work aimed to systematically estimate the risk of infection... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Infections in ruxolitinib-treated myeloproliferative neoplasm (MPN) patients were reported frequently. This work aimed to systematically estimate the risk of infection associated with ruxolitinib in MPN patients.
METHODS
The PUBMED, CNKI, EMBASE, Cochrane and CBM databases were searched to identify all related studies. Odds ratio (OR) and 95% confidence interval (CI) were used to express the difference between groups. was calculated to evaluate heterogeneity. Revman software was used to conduct the analysis.
RESULTS
Eleven randomized control trials were included in this analysis. The risk of overall infections was not different at the early stage of ruxolitinib use (OR, 95%CI: 1.23, [0.91, 1.67]). In the extension phase, overall infection was significantly lower in patients receiving ruxolitinib (OR, 95%CI: 0.53, [0.36, 0.79]). Herpes zoster infection was at higher risk both at early stage and in the extension phase (OR, 95%CI: 7.39, [1.33, 41.07]), (OR, 95%CI: 5.23, [1.46, 18.79]), respectively.
CONCLUSION
Our study suggested that ruxolitinib increased the risk of herpes zoster infection. However, current studies were not enough to estimate the effects of ruxolitinib on the risk of overall infection in patients with myeloproliferative neoplasm.
Topics: Female; Hematologic Neoplasms; Herpes Zoster; Humans; Male; Myeloproliferative Disorders; Nitriles; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic
PubMed: 34493151
DOI: 10.1080/16078454.2021.1967256 -
Cancer Imaging : the Official... Apr 2021Diagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy...
BACKGROUND
Diagnostic and treatment response criteria for the JAK2/CALR/MPL mutation-related myeloproliferative neoplasms (MPNs) are largely based on bone marrow (BM) biopsy results. However, these biopsies have several limitations, such as the risk of sampling error. Also, the prognostic impact of BM abnormalities is largely unclear. Although not currently used in clinical practice, imaging techniques might offer additional information. In this review, we investigated the value of BM, liver, and spleen imaging for diagnosis, prognostication, and response monitoring of the JAK2/CALR/MPL mutation-related MPNs (i.e. essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)).
METHODS
A systematic literature search was performed via PubMed, Embase and the Cochrane Library up to 2020 March 26th. Of 5505 identified records, 55 publications met the eligibility criteria (i.e. containing original data on the imaging appearance of BM, spleen, or liver in adult ET, PV, or MF patients, published in a peer-reviewed journal, written in English).
RESULTS
Many explorative studies described imaging features, sometimes with comparisons to clinical characteristics. Studies reporting measures of diagnostic accuracy included 1) splenic transient elastography to predict BM fibrosis grade in MF, 2) dynamic contrast-enhanced MRI to discern MF patients from ET patients and healthy controls, and 3) 18-fluorodeoxyglucose PET to detect residual disease after stem cell transplantation in MF. The diagnostic accuracies of radiography and Tc-colloid scintigraphy were derived from several other articles. Except for the study on 18-fluorodeoxyglucose PET, we established substantial concerns regarding risk of bias and applicability across these studies, using the QUADAS-2 tool. Three publications described a correlation between imaging results and prognosis, of which one quantified the effect.
CONCLUSIONS
Based on current data, MRI (T1-weighted/STIR, Dixon) seems especially promising for the evaluation of BM fat content - and indirectly cellularity/fibrosis - in MF, and possibly for estimating BM cellularity in ET/PV. 18-fluorodeoxyglucose and 18-fluorothymidine PET/CT might be useful for evaluating BM fibrosis, with good reported accuracy of the former for the diagnosis of residual disease. Further research on these and other techniques is warranted to determine their exact value. Future researchers should improve methodology and focus on evaluation of diagnostic accuracy and prognostic implications of results.
Topics: Adult; Bone Marrow; Female; Follow-Up Studies; Humans; Liver; Male; Myeloproliferative Disorders; Positron Emission Tomography Computed Tomography; Prognosis; Spleen
PubMed: 33879266
DOI: 10.1186/s40644-021-00405-7