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Leukemia Research Dec 2008Among 23 cases of myeloproliferative neoplasms (MPNs) with an associated del(5q) seen at our institution, 14 (61%) fulfilled diagnostic criteria for primary...
Among 23 cases of myeloproliferative neoplasms (MPNs) with an associated del(5q) seen at our institution, 14 (61%) fulfilled diagnostic criteria for primary myelofibrosis (PMF). Other diagnoses included polycythemia vera (PV; n=2), essential thrombocythemia (ET; n=1), post-ET myelofibrosis (n=1), systemic mastocytosis (SM; n=1), and MPN, unclassifiable (n=4). Compared to their del(5q)-negative counterparts, del(5q)-positive PMF cases were significantly more anemic (p<0.001) and thrombocytopenic (p<0.001). However, survival and leukemic transformation rates appear to be similar between the two groups. del(5q)-positive PMF was histologically characterized by a mixture of both small and monolobated megakaryocytes as well as large and bizarre megakaryocytes. When used, lenalidomide therapy induced hematological and cytogenetic remissions in del(5q)-positive PMF. The current study identifies PMF as another del(5q)-associated myeloid malignancy with characteristic megakaryocyte morphology.
Topics: Bone Marrow; Chromosomes, Human, Pair 5; Humans; Megakaryocytes; Myeloproliferative Disorders; Primary Myelofibrosis; Sequence Deletion; Survival Analysis
PubMed: 18538839
DOI: 10.1016/j.leukres.2008.04.022 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2022Patients with myelofibrosis (MF) frequently develop thrombocytopenia as a consequence of bone marrow fibrosis, splenic sequestration, and myelosuppression from an... (Review)
Review
Patients with myelofibrosis (MF) frequently develop thrombocytopenia as a consequence of bone marrow fibrosis, splenic sequestration, and myelosuppression from an inflammatory microenvironmental milieu. Thrombocytopenia occurs frequently at diagnosis, worsens with disease progression, is an independent adverse prognostic factor, and limits effective dosing of JAK2 inhibitors. Recently, pacritinib was approved for patients with MF and extreme thrombocytopenia. However, this JAK2/IRAK1 inhibitor is not primarily used to attain improvement in platelet count. In this narrative review, we discuss strategies to specifically address thrombocytopenia in MF patients including immunomodulatory drugs, synthetic androgens, hypomethylating agents and splenectomy, all of which have only modest efficacy in alleviating thrombocytopenia. We also detail transfusion approaches, including diagnostic and therapeutic consideration for platelet transfusion refractoriness. We end by discussing novel therapies, including TGFβ traps and recombinant pentraxin-2, which may increase platelet counts in MF patients. Despite recent therapeutic advancements in MF, there remains a near paucity of agents that can effectively alleviate thrombocytopenia.
Topics: Humans; Primary Myelofibrosis; Janus Kinase 2; Protein Kinase Inhibitors; Thrombocytopenia; Anemia
PubMed: 36117043
DOI: 10.1016/j.clml.2022.08.011 -
Japanese Journal of Medicine 1990Primary myelofibrosis terminating in megakaryoblastic crisis is uncommon. A case with this condition is reported. The patient, a 62-year-old female, having had primary...
Primary myelofibrosis terminating in megakaryoblastic crisis is uncommon. A case with this condition is reported. The patient, a 62-year-old female, having had primary myelofibrosis for 13 years and a splenectomy 4 years before, was admitted because of high fever, hepatomegaly, thrombocythemia and leukocytosis. On admission, blasts appeared in the peripheral blood and thereafter gradually increased in number. The blasts were proven to be of megakaryocytic lineage. To our knowledge this is the third case of primary myelofibrosis terminating in megakaryoblastic crisis to be reported in Japan.
Topics: Female; Humans; Leukemia, Megakaryoblastic, Acute; Middle Aged; Primary Myelofibrosis; Splenectomy
PubMed: 2232372
DOI: 10.2169/internalmedicine1962.29.226 -
British Journal of Hospital Medicine... Aug 2021
Topics: Autoimmune Diseases; Dermatitis; Humans; Primary Myelofibrosis
PubMed: 34431334
DOI: 10.12968/hmed.2020.0594 -
World Journal of Surgical Oncology Jun 2022Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside of the bone marrow medullary space. It is a pathophysiologic response, more often...
BACKGROUND
Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside of the bone marrow medullary space. It is a pathophysiologic response, more often associated with either a benign reactive hematological disease or a myeloproliferative neoplasm (MPN). Identification of EMH in adults is always pathologic. It is highly unlikely for a myeloproliferative neoplasm to present with inguinal lymphadenopathy. An unusual and complex case can be precisely diagnosed via a multidisciplinary approach involving experts from various modalities of laboratory. In this regard, the present case highlights the importance of an integrated approach in establishing the diagnosis.
CASE PRESENTATION
We report a case of a 61-year-old male patient of primary myelofibrosis who presented with extramedullary hematopoiesis in an inguinal lymph node. The patient initially presented with generalized symptoms including anemia, fatigue, abdominal pain, and weight loss. On examination, massive splenomegaly. Chest X-ray revealed consolidation which was secondary to right-sided pleural effusion. Therefore, he was suspected to have a lung carcinoma. However, lymph node biopsy revealed extensive fibrosis, consequently effacing the nodal architecture. An abnormal blood picture raised the possibility of bone marrow infiltration. Extensive panel of markers is tested on lymph node and bone trephine. Cytogenetic studies with G-banding analysis and fluorescence in situ hybridization (FISH) played a significant role in deriving clinical decision. Translocations identified in conventional cytogenetic workup led to the diagnosis of primary myelofibrosis. The case is being reported due to unusual presentation of PMF.
CONCLUSION
In conclusion, it is a distinctive case of myeloproliferative disorder initially presented with extramedullary hematopoiesis and through multidisciplinary workup successfully diagnosed as primary myelofibrosis. Awareness of unique clinical presentations and integrated approach towards diagnosis is the key to such challenging cases.
Topics: Bone Marrow Neoplasms; Hematopoiesis, Extramedullary; Humans; In Situ Hybridization, Fluorescence; Lymph Nodes; Male; Primary Myelofibrosis
PubMed: 35676715
DOI: 10.1186/s12957-022-02660-9 -
European Journal of Haematology Oct 2009
Comparative Study
Topics: Chromosome Aberrations; Japan; Primary Myelofibrosis; Prognosis; United States
PubMed: 19558507
DOI: 10.1111/j.1600-0609.2009.01304.x -
Haematologica Nov 2019
Topics: Cytoreduction Surgical Procedures; Disease Progression; Glomerular Filtration Rate; Humans; Kidney Function Tests; Primary Myelofibrosis; Renal Insufficiency
PubMed: 30948490
DOI: 10.3324/haematol.2018.208876 -
Clinical Lymphoma, Myeloma & Leukemia Sep 2018Molecular markers are important in guiding treatment and predicting outcome in the genomic era. Meta-analysis of molecular markers in myelofibrosis through a search of... (Meta-Analysis)
Meta-Analysis Review
Molecular markers are important in guiding treatment and predicting outcome in the genomic era. Meta-analysis of molecular markers in myelofibrosis through a search of PubMed and Medline through October 31, 2017 was performed. Markers with more than 3 studies that compared overall survival (OS) and leukemia-free survival (LFS) were analyzed. A total of 16 studies were included. Hazard ratios (HRs) for OS were as follows: IDH 2.65 (95% confidence interval [CI], 1.66-4.21), SRSF2 2.12 (95% CI, 1.18-3.79), high-risk myeloma 2.11 (95% CI, 1.70-2.61), ASXL1 1.92 (95% CI, 1.60-2.32), EZH2 1.88 (95% CI, 1.32-2.67), JAK2 1.41 (95% CI, 1.04-1.93) in the univariate analysis and 1.49 (95% CI, 0.42-5.30) in the multivariate analysis. LFS of JAK2 and SRSF2 had HRs of 1.81 (95% CI, 0.42-5.30) and 0.36 (95% CI, 0.02-6.48), respectively. In conclusion, mutations in IDH, SRSF2, and ASXL1 had worse prognosis in OS with HRs around 2. JAK2 and SRSF2 mutation were not associated with increased leukemia transformation. The adverse effect of triple-negative, which was often compared with CALR mutation, needs to be explored.
Topics: Biomarkers; Genomics; Humans; Mutation; Primary Myelofibrosis; Prognosis
PubMed: 29970342
DOI: 10.1016/j.clml.2018.06.004 -
Blood Oct 2019
Topics: Adult; Bone Marrow; Erythropoiesis; Female; Humans; Lupus Erythematosus, Systemic; Primary Myelofibrosis
PubMed: 31698419
DOI: 10.1182/blood.2019002479 -
Journal of Thrombosis and Haemostasis :... Apr 2020The risk of thromboembolism in myelofibrosis remains incompletely understood.
BACKGROUND
The risk of thromboembolism in myelofibrosis remains incompletely understood.
OBJECTIVES
To examine the association between myelofibrosis and each of venous and arterial thromboembolism.
METHODS
A cohort of 1 469 790 adults without a diagnosis of myelofibrosis was identified on 1 January 2007, from the electronic medical records of the largest health-care provider in Israel. Participants were followed until 31 December 2016 for the occurrence of myelofibrosis. Four randomly selected controls (without myelofibrosis) were matched to each case of myelofibrosis on age, sex, religious identification, and index date. The two groups were followed from the index date until 31 December 2017 for the occurrence of venous and arterial thromboembolism.
RESULTS
The study included 642 patients with myelofibrosis and 2568 matched controls. Myelofibrosis was independently associated with increased risk of venous thromboembolism but not with arterial thromboembolism. The propensity score adjusted hazard ratios (HRs) were 6.88 (95% confidence interval [CI], 2.02-23.45) for venous thromboembolism, and 0.94 (0.49-1.77) for arterial thromboembolism. Atypical sites of venous thromboembolism occurred almost exclusively in patients with myelofibrosis (four events of Budd Chiari versus none, and two mesenteric vein thrombosis events versus one) and were more likely to occur around the time of myelofibrosis diagnosis. No significant association was found between JAK2 inhibitor treatment (ruxolitinib) and the risk of venous HR 0.97 (0.30-3.12) or arterial thromboembolism 1.68 (0.78-3.62).
CONCLUSIONS
Myelofibrosis is associated with increased risk of venous thromboembolism but not of arterial thromboembolism. Atypical sites of venous thromboembolism are more frequent in myelofibrosis and are more likely to occur shortly after diagnosis.
Topics: Adult; Cohort Studies; Humans; Israel; Primary Myelofibrosis; Retrospective Studies; Risk Factors; Venous Thromboembolism
PubMed: 32017387
DOI: 10.1111/jth.14754