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Blood Advances Jan 2021Patients with myeloproliferative neoplasms (MPNs), polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have an increased risk of thrombosis. Risk of... (Meta-Analysis)
Meta-Analysis
Patients with myeloproliferative neoplasms (MPNs), polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have an increased risk of thrombosis. Risk of recurrent thrombosis can be reduced with antithrombotic therapy and/or cytoreduction, but the optimal long-term management in patients with MPN with a history of venous thromboembolism (VTE) is unknown, and clinical practice is heterogeneous. We performed a systematic review and meta-analysis of randomized trials and observational studies evaluating anticoagulant and/or antiplatelet therapy, with or without cytoreduction, in MPN patients with a history of VTE. A total of 5675 unique citations were screened for eligibility. No randomized trials were identified. Ten observational studies involving 1295 patients with MPN were included in the analysis. Overall, 23% had an arterial or recurrent venous thrombotic event on follow-up. The recurrence risk was lowest for patients on oral anticoagulation plus cytoreduction (16%); 55 of 313 (18%) with vitamin K antagonists (VKA) and 5 of 63 (8%) with direct oral anticoagulants (DOACs). In 746 analyzed patients, the risk of recurrent VTE ranged up to 33% (median 13%) and was low in 63 DOAC plus cytoreduction-treated patients (3.2%). All types of antithrombotic treatments were associated with a lower risk of recurrent VTE when combined with cytoreduction. Most studies had a high risk of bias, whereas clinical and statistical heterogeneity led to inconsistent and imprecise findings. In summary, evidence on the optimal antithrombotic treatment of VTE in patients with MPN is based on observational studies only with low certainty for all strategies. Our data suggest that a combination of anticoagulation and cytoreduction may provide the lowest recurrence risk.
Topics: Anticoagulants; Fibrinolytic Agents; Humans; Myeloproliferative Disorders; Neoplasms; Thrombosis; Venous Thromboembolism
PubMed: 33570633
DOI: 10.1182/bloodadvances.2020003628 -
Ultrasound in Obstetrics & Gynecology :... Dec 2021To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted.
METHODS
MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin-twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data.
RESULTS
Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6-7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4-13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6-5.7%) and 9.2% (95% CI, 6.6-12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6-33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4-51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5-5.7%) and 11.1% (95% CI, 6.2-17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2-93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3-100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3-17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2-17.6%), 12.1% (95% CI, 7.7-17.3%) and 7.6% (95% CI, 1.3-18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6-43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7-35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3-60.5%) of those in the IUT group and 23.3% (95% CI, 10.5-39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8-94.8%), 73.4% (95% CI, 48.1-92.3%), 100% (95% CI, 76.5-100%) and 100% (95% CI, 39.8-100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively.
CONCLUSIONS
The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Anemia, Neonatal; Blood Transfusion, Intrauterine; Diseases in Twins; Female; Fetal Diseases; Fetal Therapies; Fetofetal Transfusion; Gestational Age; Humans; Infant, Newborn; Laser Therapy; Perinatal Mortality; Polycythemia; Pregnancy; Pregnancy Outcome; Pregnancy, Twin; Premature Birth; Prognosis
PubMed: 33428243
DOI: 10.1002/uog.23585 -
Frontiers in Oncology 2020Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and...
Comparison and Implications of Mutational Profiles of Myelodysplastic Syndromes, Myeloproliferative Neoplasms, and Myelodysplastic/Myeloproliferative Neoplasms: A Meta-Analysis.
Dysplasia and proliferation are histological properties that can be used to diagnose and categorize myeloid tumors in myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). However, these conditions are not exclusive, and overlap between them leads to another classification, MDS/MPN. As well as phenotype continuity, these three conditions may have genetic relationships that have not yet been identified. This study aimed to obtain their mutational profiles by meta-analysis and explore possible similarities and differences. We reviewed screening studies of gene mutations, published from January 2000 to March 2020, from PubMed and Web of Science. Fifty-three articles were eligible for the meta-analysis, and at most 9,809 cases were involved for any gene. The top mutant genes and their pooled mutation rates were as follows: (20.2% [95% CI 11.6-30.5%]) in MDS, (39.2% [95% CI 21.7-52.0%]) in MDS/MPN, and (67.9% [95% CI 64.1-71.6%]) in MPN. Subgroup analysis revealed that leukemic transformation-related genes were more commonly mutated in high-risk MDS (MDS with multilineage dysplasia and MDS with excess blasts) than that in other MDS entities. Thirteen genes including , and had significantly higher mutation frequencies in primary myelofibrosis (PMF) compared with essential thrombocythemia and polycythemia vera; this difference distinguished PMF from MPN and likened it to MDS. Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia were similar entities but showed several mutational differences. A heat map demonstrated that juvenile myelomonocytic leukemia and MDS/MPN with ring sideroblasts and thrombocytosis were two distinct entities, whereas MDS/MPN-unclassifiable was closest to high-risk MDS. Such genetic closeness or difference reflected features in the pathogenesis, diagnosis, treatment, and progression of these conditions, and could inspire future genetic studies.
PubMed: 33117717
DOI: 10.3389/fonc.2020.579221 -
Leukemia Jun 2021Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% [51.5%-66.1%]) and 76.7% (67.4-84.0%; CHR: 48.5% [37.8-59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
Topics: Antiviral Agents; Humans; Interferon-alpha; Polycythemia Vera; Thrombocythemia, Essential
PubMed: 32868875
DOI: 10.1038/s41375-020-01020-4 -
Value in Health : the Journal of the... Jul 2020We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
OBJECTIVES
We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.
METHODS
The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found.
RESULTS
Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia.
CONCLUSIONS
There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.
Topics: Cost-Benefit Analysis; Health Status; Hematologic Neoplasms; Humans; Models, Economic; Quality of Life; Surveys and Questionnaires
PubMed: 32762998
DOI: 10.1016/j.jval.2020.04.1825 -
Journal of Clinical Medicine Jun 2020Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV)...
Twin anemia polycythemia sequence (TAPS) is a rare complication of monochorionic diamniotic (MCDA) twins. Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are used to screen for TAPS while fetal or neonatal hemoglobin levels are required for definitive diagnosis. We sought to perform a systematic review of the efficacy of MCA-PSV in diagnosing TAPS. Search criteria were developed using relevant terms to query the Pubmed, Embase, and SCOPUS electronic databases. Publications reporting diagnostic characteristics of MCA-PSV measurements (i.e., sensitivity, specificity or receiver operator curves) were included. Each article was assessed for bias using the Quality Assessment of Diagnostic Accuracy Studies II (QUADAS II) tool. Results were assessed for uniformity to determine whether meta-analysis was feasible. Data were presented in tabular form. Among publications, five met the inclusion criteria. QUADAS II analysis revealed that four of the publications were highly likely to have bias in multiple areas. Meta-analysis was precluded by non-uniformity between definitions of TAPS by MCA-PSV and neonatal or fetal hemoglobin levels. High-quality prospective studies with consistent definitions and ultrasound surveillance protocols are still required to determine the efficacy of MCA-PSV in diagnosing TAPS. Other ultrasound findings (e.g., placenta echogenicity discordance) may augment Doppler studies.
PubMed: 32512796
DOI: 10.3390/jcm9061735 -
Blood Advances Jan 2020Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea;... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is a recommended second-line treatment for the prevention of thrombosis in patients with polycythemia vera who become resistant or intolerant to hydroxyurea; however, evidence regarding its efficacy in terms of thrombosis reduction is uncertain. We searched Medline, Embase, and archives of abstracts from the European Hematology Association and the American Society of Hematology annual congresses from 2014 onward for randomized controlled trials comparing the treatment vs best available therapy (BAT). Our search retrieved 80 records; after screening of abstracts and full text, the total was reduced to 16. Evidence came from 4 randomized controlled trials, including 663 patients (1057 patients per year). We estimated a thrombosis risk ratio of 0.56 for ruxolitinib BAT, corresponding to an incidence of 3.09% and 5.51% patients per year, respectively. The number of thrombotic events reported with ruxolitinib was consistently lower than that with BAT in our sample, but, globally, the difference did not reach significance (P = .098). Hard evidence in favor of ruxolitinib is lacking; a clinical trial on selected patients at high risk of thrombosis would be warranted, but its feasibility is questionable.
Topics: Humans; Nitriles; Odds Ratio; Polycythemia Vera; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome
PubMed: 31985808
DOI: 10.1182/bloodadvances.2019001158 -
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 -
BMC Cancer Jun 2019Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV),... (Meta-Analysis)
Meta-Analysis
Systematization of analytical studies of polycythemia vera, essential thrombocythemia and primary myelofibrosis, and a meta-analysis of the frequency of JAK2, CALR and MPL mutations: 2000-2018.
BACKGROUND
Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF) have been carried out. The objective of this review is to characterize studies on BCR-ABL1-negative chronic myeloproliferative neoplasms and to compare the frequency of JAK2, MPL and CALR mutations in PV, ET and PMF.
METHOD
A systematic review of the scientific literature was conducted, as was meta-analysis with an ex-ante selection of protocol, according to phases of the PRISMA guide in three interdisciplinary databases. To guarantee reproducibility in the pursuit and retrieval of information, the reproducibility and methodological quality of the studies were evaluated by two researchers.
RESULTS
Fifty-two studies were included, the majority having been carried out in the United States, China, Brazil and Europe. The frequency of the JAK2V617F mutation ranged from 46.7 to 100% in patients with PV, from 31.3 to 72.1% in patients with ET, and from 25.0 to 85.7% in those with PMF. The frequency of the MPL mutation was 0% in PV, from 0.9 to 12.5% in ET, and from 0 to 17.1% in PMF. The CALR mutation occurred at a frequency of 0.0% in PV, whereas in ET, it ranged from 12.6 to 50%, and in PMF, it ranged from 10 to 100%. The risk of this mutation presenting in PV is 3.0 times that found for ET and 4.0 times that found for PMF.
CONCLUSION
Given the specificity and reported high frequencies of the JAK2V617F, MPL and CALR mutations in this group of neoplasms, the diagnosis of these diseases should not be made on clinical and hematological characteristics alone but should include genetic screening of patients.
Topics: Biomarkers, Tumor; Calreticulin; Genetic Heterogeneity; Genetic Testing; Humans; Janus Kinase 2; Mutation Rate; Oncogene Proteins, Fusion; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Reproducibility of Results; Thrombocythemia, Essential
PubMed: 31208359
DOI: 10.1186/s12885-019-5764-4 -
Blood Advances Jun 2019In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative... (Meta-Analysis)
Meta-Analysis
In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET). Results from epidemiologic studies on this issue, however, are inconclusive. We conducted a systematic review and meta-analysis of articles published in the last 12 years addressing the issue, according to a predefined protocol. Forty-one articles analyzing >30 000 patients met our inclusion criteria and were deemed of acceptable methodologic quality. In addition to data on thrombosis, data were collected on bleeding, hematologic evolution, secondary cancer, and death. The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups; the effect was not significant in venous thrombosis alone. Sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors confirmed the primary results. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis. The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed, whereas conclusions on hematologic evolutions and solid tumors were uncertain. To confirm the accuracy of these results, an investigation on individual patient data in a large collective archive of homogeneous patients is warranted.
Topics: Female; Hemorrhage; Humans; Leukocytosis; Male; Polycythemia Vera; Risk Factors; Thrombocythemia, Essential; Thrombosis
PubMed: 31175128
DOI: 10.1182/bloodadvances.2019000211