Characteristics of Patients With Philadelphia Negative Myeloproliferative Neoplasms at Assiut University Hospital

Overview

Classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a family of clonal chronic hematologic malignancies that include. polycythemia vera (PV), essential thrombocythemia (ET), and primary. Myelofibrosis (MF) . The classic MPNs historically have predominantly been diagnosed in older adults, with a median age at diagnosis of 60-72 years . Adults less than 40 years of age make up a largely underrepresented and therefore less studied subset of patients constituting 2.2-6.6% of yearly MPN cases in population- based study. These estimates are lower than incidence rate among patients between 40 and 49 years of age (9.1-10%), and have remained largely unchanged over the past four decades . However, with increasing trends in MPN incidence consequent to increased diagnostic recognition, better pathobiologic understanding, and more frequent JAK2/CALR/MPL mutational testing and newly revised WHO diagnostic criteria, it is conceivable that MPNs may be diagnosed at a higher frequency, in the younger patients, over time.

Diagnosis of MPN according to the revised 2008 WHO criteria is based on a. combination of clinical, morphological, and molecular parameters ( Cardinal features of Philadelphia chromosome-negative MPN are increased red blood cell (RBC). production in PV, sustained thrombocytosis in ET, and bone marrow (BM) fibrosis in PMF. Molecular markers, such as JAK2 V617F, JAK2 exon 12, and MPL mutations, have increased our knowledge of the pathogenesis of MPNs as well as the accuracy of diagnosis. Furthermore, many recent studies have reported that the calreticulin mutation (mutation in exon 9 of CALR) is found in the majority of patients with MPN with non mutated JAK2 . There are many controversies with regard to the subjectivity and the lack of reproducibility of the histological criteria. And BM assessment is not always needed, especially in PV. However, histologic evaluation of the pathologic features of megakaryocytic, granulocytic, and erythroid series and cellularity is important in differentiating MPNs, especially ET and PMF . Sometimes, patients with occult MPN present with normal blood counts because of gastrointestinal bleeding and associated iron deficiency, splenomegaly, or simply because they are in an early stage of the disorder . In cases of clinically suspicious MPN, such as intra-abdominal thrombosis with normal blood counts, careful investigation is needed. diagnostic criteria for myeloproliferative (World Health Organization) 2008. Polycythemia refers to an increase in the number of red blood cells in the body. The extra cell cause the blood to be thicker, and this, in turn, increases the risk of other health issues, such as blood clots. Maior criteria including. Hemoglobin \> 18.5 g/dL (men), \> 16.5 g/dL (women) or Presence of JAK2 V617F or JAK2 exon 12 mutation Minor criteria: BM hypercellularity with trilineage myeloproliferation Subnormal serum erythropoitin. Endogenous erythroid colony formation in vitro. Management of polycythemia: The most common treatment for polychythemia vera is having frequent blood withdrawals, using a needle in a vein (phlebotomy). Drugs that reduce the number of red blood cells If phlebotomy alone doesn't help enough, your doctor may suggest medications that can reduce the number of red blood cells in your bloodstream. Examples include: Hydroxyruea (Droxia, Hydrea), Interferon alfa-2b (Intron A), Ruxolitinib (Jakafi), Busulfan (Busulfex, Myleran) . Primary myelofibrosis (PMF) is a rare bone marrow disorder that is characterized by abnormalities in blood cell production (hematopoiesis) and scarring (formation of fibrous tissue) within the bone marrow. Bone marrow is the soft, spongy tissue that fills the center of most bones. Major criteria including. Megakaryocyte proliferation and atypiab, accompanied by either reticulin and/or collagen fibrosis, orc Not meeting WHO criteria for PV, CML, MDS, or other myeloid neoplasm Demonstration of JAK2 V617F or other clonal marker or no evidence of bone marrow fibrosis. prognosis scoring was the international prognostic scoring system (IPSS). IPSS was first produced in 2009 and was designed for application at the time of diagnosis. This IPSS was the result of data from 1054 consecutively diagnosed patients with PMF from 1980 to 2007. 4 risk groups were identified, with median survivals ranging from 23 years (high-risk) to 11.3 months (low-risk). Abnormal cytogenetic findings did not appear to affect patient outcomes. IPSS included five risk factors: age \>65 years, hemoglobin \<10 g/dl, leukocyte count \>25 x 109/L, circulating blasts ≥1% and constitutional symptoms. In 2010, DIPSS was adapted from IPSS, which allowed clinicians to use prognostic scoring at any time in the clinical course. Both IPSS and DIPSS (Dynamic IPSS) used the same five clinical risk factors to determine patient prognosis. Management of mylofibrosis: Low-risk myelofibrosis may not require immediate treatment, while people with high-risk myelofibrosis may consider an aggressive treatment, such as bone marrow transplant. For intermediate-risk myelofibrosis, treatment is usually directed at managing symptoms. Immediate treatment may not be necessary Myelofibrosis treatment may not be necessary if you aren't experiencing symptoms. You might not need treatment right away if you don't have an enlarged spleen and you don't have anemia or your anemia is very mild. Rather than treatment, your doctor is likely to monitor your health closely through regular checkups Treatments for anemia: Blood transfusions, Androgen therapy, Thalidomide and related medications. Treatments for an enlarged spleen: Chemotherapy, Targeted drug therapy, (splenectomy). If your spleen becomes so large, Radiation therapy. Bone marrow transplant. Essential thrombocytosis (ET), or primary thrombocythemia, is a rare disorder in which the body produces too many platelets for unknown reasons. This can cause abnormal blood clotting or bleeding. Majorcriteria: Sustained platelet count \> 450 × 109/LProliferation of megakaryocytes with enlarged, mature morphology Not meeting WHO criteria for PV, PMF, CML, MDS or other myeloid neoplasm Demonstration of JAK2 V617F or other clonal marker, or no evidence for reactive Thrombocytosis. Patients with low-risk ET are usually managed with low-dose aspirin, whereas treatment of high-risk ET is based on the use of cytoreductive therapy, with hydroxyurea as the drug of choice and IFN-α being reserved for young patients or pregnant women