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World Journal of Clinical Oncology Jun 2024Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs... (Review)
Review
Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.
PubMed: 38946827
DOI: 10.5306/wjco.v15.i6.717 -
Military Medicine Jun 2024The article presents a clinical case of peculiarities of clinical manifestations, diagnostic and therapeutic approaches of undiagnosed chronic myeloproliferative...
A Clinical Case of Timely Diagnosis and Successful Treatment of Budd-Chiari Syndrome With Fulminant Cytolysis in the Setting of a First-time Diagnosed Myeloproliferative Disease.
The article presents a clinical case of peculiarities of clinical manifestations, diagnostic and therapeutic approaches of undiagnosed chronic myeloproliferative disease, on the background of which Budd-Chiari syndrome (BCS) developed. The results of clinical course, examination, and treatment of a patient with BCS as a manifestation of the hidden course of primary myelofibrosis with the presence of somatic mutation (V617F) in Janus-tyrosine kinase-2 (JAK2) gene in myeloid cells are presented. Standard clinical and laboratory examinations, and cytomorphologic and histologic examination of bone marrow were used. The diagnosis of BCS was confirmed by ultrasound (US) Doppler examination of the portal system vessels. Symptomatic therapy resulted in insignificant positive results. The analysis of this clinical case showed that the development of BCS was due to a chronic myeloproliferative disease that was not diagnosed before the development of thrombosis. Hepatic vein thrombosis was accompanied by the development of fulminant cytolytic syndrome. Along with symptomatic therapy, patient K., female, 32 years old, underwent transjugular intrahepatic portosystemic shunting 1 month after the first symptoms of BCS appeared, which contributed to a significant clinical effect. Seven years after the installation of 4 transjugular intrahepatic portosystemic shunts, the patient's condition remains satisfactory. The uniqueness of this clinical case lies in the presence of 2 serious diseases at the same time: myeloproliferative pathology (primary myelofibrosis) JAK2-positive variant and BCS. Timely diagnosis of both hematological diseases and their complication in the form of hepatic vein thrombosis with fulminant cytolytic syndrome allowed timely prescription of adequate treatment with a good clinical response.
PubMed: 38935394
DOI: 10.1093/milmed/usae331 -
Blood Jun 2024
Topics: Humans; Mutation; Myeloproliferative Disorders; Carrier Proteins; Nuclear Proteins; Primary Myelofibrosis; Male; Bone Marrow
PubMed: 38935362
DOI: 10.1182/blood.2024025290 -
Journal of Clinical Medicine Jun 2024Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare...
Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients ( = 0.049, < 0.001, < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients ( = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.
PubMed: 38929918
DOI: 10.3390/jcm13123390 -
International Journal of Molecular... Jun 2024Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders...
Assessment of Total Antioxidant Capacity, 8-Hydroxy-2'-deoxy-guanosine, the Genetic Landscape, and Their Associations in -Negative Chronic and Blast Phase Myeloproliferative Neoplasms.
Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2'-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls ( = 0.03), particularly in ET ( = 0.04) and PMF ( = 0.01). -positive MPNs had higher TAC than controls ( = 0.002) and triple-negative MPNs ( = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects ( = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; = 0.05), i.e., ET (OR = 2.36; = 0.03) and PMF (OR = 2.11; = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; = 0.62) or sAML (OR = 1.89; = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history.
Topics: Humans; Male; Female; 8-Hydroxy-2'-Deoxyguanosine; Middle Aged; Aged; Myeloproliferative Disorders; Antioxidants; Adult; Oxidative Stress; Aged, 80 and over; Blast Crisis; Fusion Proteins, bcr-abl; Primary Myelofibrosis
PubMed: 38928358
DOI: 10.3390/ijms25126652 -
Expert Opinion on Pharmacotherapy Jun 2024Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, a potential for leukemic... (Review)
Review
INTRODUCTION
Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, a potential for leukemic transformation, and increased mortality. Patients who are ineligible for stem cell transplant rely on pharmacologic therapies of noncurative intent, whose cornerstone consists of JAK inhibitors (JAKi). While current JAKi are efficacious in controlling symptoms and splenic volume, none meaningfully reduce clonal burden nor halt disease progression, and patients oftentimes develop JAKi intolerant, relapsed, or refractory MF. As such, there remains an urgent necessity for second-line options and novel therapies with disease-modifying properties.
AREAS COVERED
In this review, we delineate the mechanistic rationale, along with the latest safety and efficacy data, of investigational JAKi-based MF treatment strategies, with a focus on JAKi monotherapies and combinations of novel agents with approved JAKi. Our literature search consisted of extensive review of PubMed and clinicaltrials.gov.
EXPERT OPINION
A myriad of promising MF-directed therapies are in late-phase studies. Following their approval, treatment selection should be tailored to patient-specific treatment goals and disease characteristics, with an emphasis on combination therapies of JAKi with novel agents of differing mechanistic targets that possess anti-clonal properties, in attempt to alter disease course and concurrently limit dose-dependent JAKi toxicities.
PubMed: 38919983
DOI: 10.1080/14656566.2024.2372453 -
Blood Advances Jun 2024We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013...
We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.
PubMed: 38916866
DOI: 10.1182/bloodadvances.2024013451 -
Annals of Hematology Jun 2024Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies....
Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.
PubMed: 38907072
DOI: 10.1007/s00277-024-05847-0 -
Indian Journal of Pathology &... Jun 2024Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct...
BACKGROUND
Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm.
MATERIALS AND METHODS
This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details.
RESULTS
These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate.
CONCLUSION
Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.
PubMed: 38904435
DOI: 10.4103/ijpm.ijpm_474_23 -
Blood Cells, Molecules & Diseases Jun 2024TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal...
TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei ("dysmorphic megakaryocyte"), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome.
PubMed: 38901333
DOI: 10.1016/j.bcmd.2024.102870