Prefibrotic primary myelofibrosis

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Prefibrotic primary myelofibrosis
Other namesPre-PMF, Early stage myelofibrosis
Specialty Hematology and oncology

Prefibrotic primary myelofibrosis (Pre-PMF) is a rare blood cancer, classified by the World Health Organization as a distinct type of myeloproliferative neoplasm in 2016. [1] The disease is progressive to overt primary myelofibrosis, though the rate of progression is variable and not all patients progress. Symptoms and presentation can mimic essential thrombocythemia, with the main differentiator for pre-PMF being the presence of fibrosis in the bone marrow.

Contents

Diagnosis

A bone marrow examination is required for diagnosis.

Major Criteria

The bone marrow histology should demonstrate the following: [2]

Minor Criteria

According to the WHO, at least one of these minor criteria should be present: [1]

Comparison with primary myleofibrosis

Reticulin or collagen fibrosis grade 2 or 3 is a diagnostic criteria for primary myelofibrosis.

Comparison with Essential Thrombocythemia

Both pre-PMF and Essential thrombocythemia can share diagnostic similarities, such as a proliferation of megakaryocytes and a presence of a mutation. The presence of Reticulin fibrosis in pre-PMF provides the clearest distinction between the two.

Treatment

Patients considered low risk for thrombosis or major bleeding should be observed only. Low-dose aspirin is recommended for patients without a history of thrombosis. For intermediate risk patients, symptom driven therapy for anaemia or constitutional symptoms.[ citation needed ]

For high risk patients with a history of thrombosis, oral anticoagulants and cytoreductive drugs such as hydroxycarbamide are recommended, and the patient should be treated as in primary myelofibrosis. [1] [3]

Prognosis

Prognosis of pre-PMF currently suffers from a lack of multi-center data, with several biases resulting from the disease being newly distinct in WHO's 2016 reclassification. The 10 year cumulative incidence of progression to overt PMF is between 9.7 and 31.5%. The 10 year incidence of transformation into acute myeloid leukemia ranges from 5.8% to 12%. [4]

A prognostic scoring model designed specifically for pre-PMF does not yet exist, but the International Prognostic Scoring System can be used to predict survival in pre-PMF patients. [5] A multi-center study on reclassified PMF patients showed median survival of pre-PMF patients at 17.6 years compared with 7.2 years for overt PMF patients. [1] However, another study showed 98% of pre-PMF patients were alive after 10 years from diagnosis and while overt PMF patients showed a median survival of 16.6 years, pre-PMF median survival was not able to be calculated as more than 50% of patients were still alive at the time of publication. [6]

History

First described in 1976, pre-PMF was not introduced into the WHO's classification of tumors until 2001, and not formally classified as a distinct entity until the 2016 revision. [1]

Related Research Articles

Polycythemia vera Medical condition

Polycythemia vera is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets.

Paroxysmal nocturnal hemoglobinuria Medical condition

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of venous blood clot formation, are incompletely understood.

Thrombocytopenia Medical condition

Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in 20% of medical patients and a third of surgical patients.

Megakaryocyte

A megakaryocyte is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte.

Chronic myelogenous leukemia Medical condition

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes and their precursors is found. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome.

Thrombocythemia Medical condition

Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L.

Essential thrombocythemia Medical condition

Essential thrombocythemia (ET) is a rare chronic blood cancer characterised by the overproduction of platelets (thrombocytes) by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukemia or myelofibrosis. It is one of four myeloproliferative neoplasms that occur when the body makes too many white or red blood cells, or platelets).

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is growth of abnormal cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL gene markers. In PMF, the healthy marrow is replaced by scar tissue (fibrosis), resulting in a lack of production of normal blood cells. Symptoms include anemia, increased infection and an enlarged spleen (splenomegaly).

Myeloproliferative neoplasm Medical condition

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

Anagrelide

Anagrelide is a drug used for the treatment of essential thrombocytosis, or overproduction of blood platelets. It also has been used in the treatment of chronic myeloid leukemia.

GATA1

GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.

Thrombopoietin receptor

The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 is a protein that in humans is encoded by the MPL oncogene.

Hepatic veno-occlusive disease (VOD) or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given before a bone marrow transplant and/or excessive exposure to hepatotoxic pyrrolizidine alkaloids. It is classically marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood. The name sinusoidal obstruction syndrome (SOS) is preferred if hepatic veno-occlusive disease happens as a result of chemotherapy or bone marrow transplantation.

Basophilia Medical condition

Basophilia is the condition of having greater than 200 basophils/μL in the venous blood.

Acute megakaryoblastic leukemia Medical condition

Acute megakaryoblastic leukemia (AMKL) is life-threatening leukemia in which malignant megakaryoblasts proliferate abnormally and injure various tissues. Megakaryoblasts are the most immature precursor cells in a platelet-forming lineage; they mature to promegakaryocytes and, ultimately, megakaryocytes which cells shed membrane-enclosed particles, i.e. platelets, into the circulation. Platelets are critical for the normal clotting of blood. While malignant megakaryoblasts usually are the predominant proliferating and tissue-damaging cells, their similarly malignant descendants, promegakaryocytes and megakaryocytes, are variable contributors to the malignancy.

Acute panmyelosis with myelofibrosis (APMF) it is a poorly defined disorder that arises as either a clonal disorder, or following toxic exposure to the bone marrow.

Janus kinase inhibitors, also known as JAK inhibitors or jakinibs, are a type of medication that functions by inhibiting the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway.

Ruxolitinib

Ruxolitinib, sold under the brand names Jakafi and Jakavi, is a medication for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow; polycythemia vera (PCV), when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi. Ruxolitinib is a janus kinase inhibitor.

Fedratinib, sold under the brand name Inrebic, is an anti-cancer medication used to treat myeloproliferative diseases including myelofibrosis. It is used in the form of fedratinib hydrochloride capsules that are taken by mouth. It is a semi-selective inhibitor of Janus kinase 2 (JAK-2). It was approved by the FDA on 16 August 2019.

Momelotinib Chemical compound

Momelotinib (INN, formerly GS-0387, CYT-387) is an inhibitor of Janus kinases JAK1 and JAK2, acting as an ATP competitor with IC50 values of 11 and 18 nM, respectively. The inhibitor is significantly less active towards other kinases, including JAK3 (IC50 = 0.16 μM).

References

  1. 1 2 3 4 5 Finazzi, Guido; Vannucchi, Alessandro M.; Barbui, Tiziano (2018-11-07). "Prefibrotic myelofibrosis: treatment algorithm 2018". Blood Cancer Journal. 8 (11): 104. doi:10.1038/s41408-018-0142-z. ISSN   2044-5385. PMC   6221891 . PMID   30405096.
  2. ↑ Arber, Daniel A.; Orazi, Attilio; Hasserjian, Robert; Thiele, Jürgen; Borowitz, Michael J.; Le Beau, Michelle M.; Bloomfield, Clara D.; Cazzola, Mario; Vardiman, James W. (2016-05-19). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi: 10.1182/blood-2016-03-643544 . ISSN   0006-4971. PMID   27069254.
  3. ↑ Barbui, Tiziano; Thiele, Juergen; Gisslinger, Heinz; Orazi, Attilio; Vannucchi, Alessandro M.; Gianelli, Umberto; Beham‐Schmid, Christine; Tefferi, Ayalew (2019). "Comments on pre-fibrotic myelofibrosis and how should it be managed". British Journal of Haematology. 186 (2): 358–360. doi: 10.1111/bjh.15840 . ISSN   1365-2141. PMID   30847907.
  4. ↑ Barbui, Tiziano; Thiele, Juergen; Gisslinger, Heinz; Orazi, Attilio; Vannucchi, Alessandro M.; Gianelli, Umberto; Beham‐Schmid, Christine; Tefferi, Ayalew (2019). "Comments on pre-fibrotic myelofibrosis and how should it be managed". British Journal of Haematology. 186 (2): 358–360. doi: 10.1111/bjh.15840 . ISSN   1365-2141. PMID   30847907.
  5. ↑ Rumi, Elisa; Sant’Antonio, Emanuela; Boveri, Emanuela; Pietra, Daniela; Cavalloni, Chiara; Roncoroni, Elisa; Astori, Cesare; Arcaini, Luca (2018-07-03). "Diagnosis and management of prefibrotic myelofibrosis". Expert Review of Hematology. 11 (7): 537–545. doi:10.1080/17474086.2018.1484280. ISSN   1747-4086. PMID   29862872. S2CID   44097453.
  6. ↑ Barosi, Giovanni; Rosti, Vittorio; Bonetti, Elisa; Campanelli, Rita; Carolei, Adriana; Catarsi, Paolo; Isgrò, Antonina M.; Lupo, Letizia; Massa, Margherita; Poletto, Valentina; Viarengo, Gianluca (2012-04-20). "Evidence that Prefibrotic Myelofibrosis Is Aligned along a Clinical and Biological Continuum Featuring Primary Myelofibrosis". PLOS ONE. 7 (4): e35631. Bibcode:2012PLoSO...735631B. doi:10.1371/journal.pone.0035631. ISSN   1932-6203. PMC   3334973 . PMID   22536419.
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