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Journal of Comparative Effectiveness... Sep 2023Patients with polycythemia vera (PV), a rare and chronic blood cancer, are at a higher risk for thromboembolic events, progression to myelofibrosis, and leukemic...
Patients with polycythemia vera (PV), a rare and chronic blood cancer, are at a higher risk for thromboembolic events, progression to myelofibrosis, and leukemic transformation. In 2021, ropeginterferon alfa-2b-njft (BESREMi) was approved in the US to treat adults with PV. The purpose of this study is to estimate the cost-effectiveness of ropeginterferon alfa-2b-njft, used as a first- or second-line treatment, for the treatment of patients with PV in the US. A Markov cohort model was developed from the healthcare system perspective in the United States. Model inputs were informed by the PROUD-PV and CONTINUATION-PV studies and published literature. The model population included both low-risk and high-risk patients with PV. The model compared ropeginterferon alfa-2b-njft used either as first- or second-line versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. Over the modeled lifetime, ropeginterferon alfa-2b-njft provided an additional 0.4 higher quality-adjusted life years (QALYs) and 0.4 life-years with an added cost of USD60,175, resulting in a cost per QALY of USD141,783. The model was sensitive to treatment costs, the percentage of patients who discontinue hydroxyurea, the percentage of ropeginterferon alfa-2b-njft users who switch to monthly dosing, the percentage of ropeginterferon alfa-2b-njft users as 2nd line treatment, and the treatment response rates. A younger patient age at baseline and a higher percentage of patients with low-risk disease improved the cost-effectiveness of ropeginterferon alfa-2b-njft. Ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea.
Topics: Adult; Humans; Polycythemia Vera; Interferon-alpha; Hydroxyurea; Interferon alpha-2; Cost-Benefit Analysis
PubMed: 37531245
DOI: 10.57264/cer-2023-0066 -
BMC Medical Genomics Jul 2023As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood.
BACKGROUND
As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood.
METHODS
37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis.
RESULTS
The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent.
CONCLUSION
This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.
Topics: Humans; Altitude Sickness; Altitude; Polycythemia; Erythrocytes
PubMed: 37507679
DOI: 10.1186/s12920-023-01613-9 -
Annals of Hematology Jan 2024There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we...
There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era.
Topics: Humans; Aged; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis; Prospective Studies
PubMed: 37946031
DOI: 10.1007/s00277-023-05528-4 -
Leukemia Research Jan 2024BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are classically represented by polycythemia vera, essential thrombocythemia, and primary myelofibrosis.... (Review)
Review
BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are classically represented by polycythemia vera, essential thrombocythemia, and primary myelofibrosis. BCR::ABL1-negative MPNs are significantly associated with morbidity and mortality related to an increased risk of thrombo-hemorrhagic events. They show a consistent association with splanchnic vein thrombosis (SVT), either represented by the portal, mesenteric or splenic vein thrombosis, or Budd-Chiari Syndrome. SVT is also a frequent presenting manifestation of MPN. MPNs associated with SVT show a predilection for younger women, high association with JAK2V617F mutation, low JAK2V617F variant allele frequency (generally <10 %), and low rates of CALR, MPL, or JAK2 exon 12 mutations. Next-Generation Sequencing techniques have contributed to deepening our knowledge of the molecular landscape of such cases, with potential diagnostic and prognostic implications. In this narrative review, we analyze the current perspective on the molecular background of MPN associated with SVT, pointing as well future directions in this field.
Topics: Humans; Female; Myeloproliferative Disorders; Venous Thrombosis; Polycythemia Vera; Thrombocythemia, Essential; Mutation; Calreticulin; Janus Kinase 2
PubMed: 38016412
DOI: 10.1016/j.leukres.2023.107420 -
BMJ Case Reports Oct 2023We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine....
We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission.
Topics: Humans; Capillary Leak Syndrome; Cardiac Tamponade; COVID-19; COVID-19 Vaccines; Pericardial Effusion
PubMed: 37813549
DOI: 10.1136/bcr-2023-256527 -
Platelets Dec 2024Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of...
Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical "MF-like" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.
Topics: Humans; Bone Marrow; Megakaryocytes; Polycythemia Vera; Primary Myelofibrosis; Proteomics; Thrombocythemia, Essential; Transcription Factor 3
PubMed: 38303515
DOI: 10.1080/09537104.2024.2304173 -
Clinical Advances in Hematology &... Mar 2024The treatment landscape for BCR/ABL-negative myeloproliferative neoplasms (MPNs), driven by and mutations, has evolved significantly over the last decade. Recent... (Review)
Review
The treatment landscape for BCR/ABL-negative myeloproliferative neoplasms (MPNs), driven by and mutations, has evolved significantly over the last decade. Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. Many clinical trials have documented the safety and efficacy of IFN-α therapy in PV and essential thrombocythemia, the classical BCR/ABL-negative MPNs. Used off-label for more than 30 years as a cytoreductive agent, IFN-α therapy promotes significant clinical, hematologic, and molecular responses. In some IFN-α-treated patients, partial or complete reduction of the mutant allele burden may lead to a durable measurable residual disease state, owing to the ability of long-term IFN-α therapy to selectively deplete mutant -harboring hematopoietic stem cells. Pegylated IFN-α forms were developed to improve the drug stability and tolerability of first-generation IFN-α therapeutics. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.
Topics: United States; Humans; Myeloproliferative Disorders; Interferon-alpha; Immunotherapy; Neoplasm, Residual; Polyethylene Glycols
PubMed: 38446475
DOI: No ID Found -
Pathology, Research and Practice Aug 2023Paraneoplastic syndromes are complex clinical manifestations that occur because of the underlying malignancy in which the malignant cells produce hormones, cytokines,... (Review)
Review
Paraneoplastic syndromes are complex clinical manifestations that occur because of the underlying malignancy in which the malignant cells produce hormones, cytokines, peptides or antibodies that causes symptoms and may affect multiple organ systems. These paraneoplastic conditions may be associated with different solid and hematological malignancies. Multiple Myeloma (MM) accounts for 10-15 % of hematological malignancies and 1-2 % of all malignancies. It is associated with some atypical clinical and laboratory paraneoplastic manifestations. Although there is a low incidence of these paraneoplastic, significant knowledge of these manifestations may assist in making a differential diagnosis in cases of doubt. The clinical presentation may vary and be evident even before or after the diagnosis of malignancy. These include vascular, neurological, dermatological, physiological, and other atypical conditions. Furthermore, these rare paraneoplastic manifestations need more valid, relevant scientific information, as most information about these conditions is derived from case reports. After the literature search, we have reported the paraneoplastic manifestations associated with multiple myeloma, published in the English literature, and the cognate management in this review article. To our knowledge, this is the first review article discussing various paraneoplastic manifestations of multiple myeloma.
PubMed: 37478520
DOI: 10.1016/j.prp.2023.154689 -
Ultrasound in Obstetrics & Gynecology :... Oct 2023Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of...
OBJECTIVE
Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies.
METHODS
This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention.
RESULTS
Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124).
CONCLUSION
Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
PubMed: 37204929
DOI: 10.1002/uog.26256 -
African Journal of Reproductive Health Nov 2023We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical... (Meta-Analysis)
Meta-Analysis
Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.
We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Infant, Premature; Umbilical Cord Clamping; Perinatal Death; Umbilical Cord; Hematocrit
PubMed: 38053339
DOI: 10.29063/ajrh2023/v27i11.11