MF presentation is diverse. About one-third of MF patients remain asymptomatic for prolonged periods of time, while others develop debilitating constitutional symptoms and signs of bone marrow failure [1]. Regarding the former, fatigue, fever, dyspnea, night sweats, and weight loss are most commonly reported. Patients may become cachectic. Additional symptoms are usually related to hematological abnormalities: There is a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow, which may give rise to leukocytosis and thrombocytosis, along with circulatory disorders due to thrombophilia, thrombosis, and disseminated intravascular coagulation [2].

As the disease progresses, the reactive deposition of fibrous connective tissue increasingly interferes with hematopoiesis, and patients develop cytopenias. Anemia is common in MF patients, may increase fatigue and weakness, induce pallor and cyanosis. Anemic patients may also claim headaches and dizziness. Leukopenia, on the other hand, predisposes to infections. Thrombocytopenia is less frequently observed than thrombocytosis and renders patients prone to bleeding.

In an intent to compensate for bone marrow failure, extramedullary hematopoiesis is stimulated, entailing hepatomegaly, splenomegaly, and possibly bone pain and osteosclerosis. Besides abnormal laboratory results, palpable organomegaly may indeed be the only finding on clinical examination.

• Splenomegaly

  Splenomegaly is one of the major clinical manifestations of MF and is directly linked to splenic extramedullary hematopoiesis (EMH). [ncbi.nlm.nih.gov]

  Similarly, their use in patients with splenomegaly due to splanchnic vein thrombosis in which the mechanism of splenomegaly is probably different from that of typical myelofibrosis is warranted as well. [jhoonline.biomedcentral.com]

  Splenomegaly [ 1 ] First-line: hydroxycarbamide (in the absence of cytopenias). [patient.info]

• Anemia

  In patients whose only disease manifestation is anemia, we use anti-anemia medications. [journals.lww.com]

  Myelofibrosis: Spontaneous scarring (fibrosis) of the bone marrow that disrupts the normal production of blood cells, leading to severe anemia and enlargement of the spleen and liver. Myelofibrosis usually begins slowly and worsens over time. [medicinenet.com]

  The main adverse effects of ruxolitinib are anemia and thrombocytopenia. [merck.com]

• Pain

  During the last 3 years of his life, he suffered from intractable bone pain that was resistant to medical, analgesic and physical therapies. However, significant pain alleviation was achieved shortly after starting chiropractic treatment. [doi.org]

  Pain. A severely enlarged spleen can cause abdominal pain and back pain. Growths in other areas of your body. [mayoclinic.org]

  Bone pain: Can occur and may need strong pain killers. Thrombosis: The risk of a blood clot is increased in patients with MF. AML: Between 20-30% of patients will develop leukaemia. [mpnvoice.org.uk]

  • Excessive sweating during sleep • Fever • Frequent infections • Bone pain Most of these symptoms can be managed with medications and other techniques. [cancercare.org]

• Fatigue

  He had fatigue, night sweats, and unexpected weight loss. [targetedonc.com]

  CASE PRESENTATION: We report a 36-year-old pregnant woman who presented with cytopenia, fatigue, vomiting, and diarrhea for 20 days on the background of newly diagnosed myelofibrosis secondary to gastric signet ring adenocarcinoma. [ncbi.nlm.nih.gov]

  Ruxolitinib (Jakafi) can target the JAK2 protein and can reduce spleen size, improve symptoms like itching or fatigue and reduce the white blood cell count. It has been shown to improve survival. [cancer.columbia.edu]

  Other symptoms may include: Fatigue A general feeling of discomfort Difficulty breathing Weight loss Fever and night sweats Anemia Abnormal bleeding Patients with myelofibrosis have an increased risk of bleeding. [stanfordhealthcare.org]

• Fever

  Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided. [ncbi.nlm.nih.gov]

  Constitutional symptoms include fevers, pruritus, and the one that I find to be the most troubling is early satiety leading to weight loss. Once that starts to develop, patients tend to have a more rapid decline. [onclive.com]

  CLINICAL FEATURES • painful splenic infarct -fever & pleuritic chest pain 10. [slideshare.net]

• Splenectomy

  To assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for postsplenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, [ncbi.nlm.nih.gov]

  Splenectomy Another option may be to have an operation to remove your spleen (a splenectomy). There can be complications after a splenectomy: your doctor will discuss the pros and cons with you to help you decide if the procedure is right for you. [bloodwise.org.uk]

  Splenectomy for patients with myelofibrosis and myeloid metaplasia: Pretreatment variables and outcome prediction. Leukemia. 1993;7:200–206. PubMed Google Scholar 39. Faoro LN, Tefferi A, Mesa RA. [doi.org]

• Abdominal Fullness

  Symptoms may include any of the following: Abdominal fullness, pain, or feeling full before finishing a meal (because of an enlarged spleen) Bone pain Easy bleeding, bruising Fatigue Increased likelihood of getting an infection Pale skin Shortness of [nlm.nih.gov]

  Patients most commonly present with fatigue due to anemia or abdominal fullness related to splenomegaly. Uncommon presentations include bleeding and bone pain. On examination, splenomegaly is almost invariably present and is commonly massive. [accessmedicine.mhmedical.com]

  A sense of abdominal fullness caused by enlargement of the spleen Bone pain Bruising and easy bleeding due to declining platelets Fatigue Increased susceptibility to infection Pallor and shortness of breath related to anemia Hyperuricemia (a high level [cancer.columbia.edu]

  Symptoms Symptoms may include any of the following: Abdominal fullness, pain, or feeling full before finishing a meal (because of an enlarged spleen) Bone pain Easy bleeding, bruising Fatigue Increased likelihood of getting an infection Pale skin Shortness [m.ufhealth.org]

• Abdominal Distension

  Abstract A 35-year-old man with a 12-year history of idiopathic myelofibrosis (IMF) presented in 2014 with fatigue and abdominal distension. [ncbi.nlm.nih.gov]

  distension/fluid retention (if portal hypertension or increased blood pressure within the portal vein is present) Compromised liver function Abnormal growth of blood forming cells outside of the bone marrow Routine medical examinations including complete [mpnresearchfoundation.org]

  The symptoms mainly include those associated with splenomegaly (abdominal distension and pain, early satiety, splenic infarction, dyspnoea, and diarrhoea) and constitutional symptoms such as fatigue, cachexia, pruritus, bone pain, weight loss, and fever [journals.sagepub.com]

• Thrombosis

  In this review, we discuss the frequency of thrombosis and bleeding in patients with MF, including prefibrotic PMF and their established and potential risk factors. KEYWORDS: Bleeding; Myelofibrosis; Prefibrotic; Risk factors; Thrombosis [ncbi.nlm.nih.gov]

  Preventing major bleeding and thrombosis Specific prognostic scores for predicting the risk of bleeding and thrombosis in PMF patients are not available. [nature.com]

  In fact, 82% of patients with splanchnic vein thrombosis bore JAK2V617F mutation with respect to 59.5% of patients without splanchnic vein thrombosis. [journals.plos.org]

  Disease ECG Echocardiography Heart Failure Hypertension Invasive Hemodynamics Miscellaneous Mitral Regurgitation Mitral Stenosis PCI and Cardiac Surgery Pre-operative Assessment Risk Scores Shunts Syncope Treadmill Testing Body Imaging Obstetrical imaging Thrombosis [qxmd.com]

• Palpitations

  Symptoms of Myelofibrosis Weakness and fatigue; heart palpitations; shortness of breath; paleness (pallor); loss of weight and appetite (due to anemia) Easy bleeding and bruising; clusters of pinpoint-size hemorrhages (petechiae) on the skin (due to platelet [healthcommunities.com]

  Symptoms of myelofibrosis include: fatigue weight loss paleness fever sweating weakness heart palpitations shortness of breath itching feeling full after eating a small amount of food stomach pain or discomfort pain in the left shoulder or upper left [encyclopedia.com]

  Symptoms of anaemia are common and include unexplained tiredness, weakness, shortness of breath and palpitations. [leukaemia.org.au]

• Arthralgia

  The most common symptoms of MF include: Fatigue Sweats (which may be predominantly at night) Itching (pruritus) – this may be worse after baths or showers Bone pain (arthralgia) Muscle pain (myalgia) Weight loss Fever Diagnosis will usually be made following [leukaemiacare.org.uk]

  […] nausea (24%), vomiting (21%), and constipation (10%). 94, 98 – 101 Patients have also been reported to experience renal dysfunction (10%-64%, usually nonprogressive at the start of treatment and improving after a dose reduction), skin rash (4%-39%), arthralgia [journals.sagepub.com]

• Night Sweats

  So, malfunctioning bone marrow, anemia—low platelets in some patients—and low white cell count coupled with a very large spleen, enlargement of the liver, and very poor quality of life—bone aches and pains, night sweating, low-grade fevers, itching, night [onclive.com]

  Other symptoms may include: Fatigue A general feeling of discomfort Difficulty breathing Weight loss Fever and night sweats Anemia Abnormal bleeding Patients with myelofibrosis have an increased risk of bleeding. [stanfordhealthcare.org]

  Case: 72-Year-Old Man Diagnosed With Primary Myelofibrosis December 2018 A 72-year old man presents to primary care physician with complaints of fatigue, headache, night sweats, poor appetite, and 10-15lb weight loss over past few months; report of increased [targetedonc.com]

  […] fatigue, fever, night sweats and weight loss. [mpnresearchfoundation.org]

• Pruritus

  The WG focused on the seven core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain. [ncbi.nlm.nih.gov]

  MF patients can also suffer from debilitating constitutional symptoms, such as drenching night sweats, fatigue, severe itching (pruritus), abdominal pain, fever and bone pain. [geron.com]

  Clinical manifestations depend on the type of blood cell(s) affected and may include severe anemia, pallor, petechiae, ecchymosis, bleeding, thrombosis, pancytopenia, pruritus, hypermetabolic state, marked hepato/splenomegaly, and/or constitutional symptoms [orpha.net]

• Petechiae

  Clinical manifestations depend on the type of blood cell affected and may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension. [orpha.net]

  Spontaneous bleeding may occur and vary from insignificant cutaneous petechiae to severe, life-threatening gastrointestinal tract bleeding. [patient.info]

• Epistaxis

  Grade 3/4 adverse events of epistaxis (n = 1), asymptomatic QT prolongation (n = 1), and bradycardia (n = 1) occurred in three patients within the first 3 months of retreatment. One death due to catheter-associated sepsis occurred. [ncbi.nlm.nih.gov]

  A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. [labmedonline.org]

• Headache

  Case: 72-Year-Old Man Diagnosed With Primary Myelofibrosis December 2018 A 72-year old man presents to primary care physician with complaints of fatigue, headache, night sweats, poor appetite, and 10-15lb weight loss over past few months; report of increased [targetedonc.com]

  Side effects can include: Bleeding Infection Bruising Dizziness Headaches The only treatment that could potentially cure the disease is a stem cell transplant. [webmd.com]

  Diagnosis of Dementia with Lewy Bodies (DLB) Diagnose patients with dementia with Lewy Bodies based on the 2017 criteria Arteriovenous Malformation Coma/Level of Consciousness Demyelinating Disease Dermatome Map Functional Outcome Head & Neck Trauma Headache [qxmd.com]

  The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache. These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. [jakafi.com]

• Dizziness

  Side effects can include: Bleeding Infection Bruising Dizziness Headaches The only treatment that could potentially cure the disease is a stem cell transplant. [webmd.com]

  The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache. These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. [jakafi.com]

• Tingling

  You may also get side effects from this treatment such as feeling tired or drowsy, constipation and numbness or tingling in your hands and feet. [bloodwise.org.uk]

  Some of the most common treatment side effects include: nausea dizziness pain or tingling in the hands and feet fatigue shortness of breath fever temporary hair loss Side effects usually go away after your treatment is completed. [healthline.com]

  The side effects can include feeling tired or sleepy, constipation and numbness or tingling of the hands and feet. If you feel sleepy, it’s important not to drive. Thalidomide can cause birth defects, so it should not be given to pregnant women. [macmillan.org.uk]

• Paresthesia

  [xviii], [xix], [xx] Potential side effects of older therapies include progression to leukemia, enlarged liver (hepatomegaly), drowsiness, constipation, fatigue, burning or prickling sensation (paresthesias), and low white blood cell count (neutropenia [cmlsociety.org]

  Hepatic alterations are the main toxicity; they appear in Immunomodulating drugs Thalidomide, at 100 to 200 mg/day, is associated with high withdrawal due to side effects such as constipation, fatigue, paresthesiae, sedation, hematologic toxicity, and [bloodjournal.org]

• Lethargy

  Symptoms The symptoms of the disease are caused by a change in the blood count (most common is an increase in the thrombocyte count and/or anemia) and are very unspecific, ranging from tiredness, lethargy and bloodclotting to an increased susceptibility [aoporphan.com]

The World Health Organization has defined diagnostic criteria for primary MF and distinct myeloproliferative neoplasms that may ensue fibrotic changes of the bone marrow [3]. Due to the diversity of conditions that may be associated with reactive myelofibrosis, there are no common guidelines on this matter. In general, the diagnosis of MF is based on morphologic features of the bone marrow, molecular and genetic findings, along with laboratory data:

• The examination of bone marrow biopsy specimens should reveal megakaryocytic proliferation and megakaryocytic atypia, which are usually accompanied by reticulin or collagen fibrosis. In the prefibrotic phase of primary MF, reticulin and collagen fibrosis may be absent, but increased bone marrow cellularity with granulocytic proliferation and reduced erythropoiesis may be observed [4].
• Genetic studies should be realized to determine the presence of driver mutations of genes JAK2, CALR, and MPL. Due to the high prevalence of the JAK2 V617F mutation, first analyses generally aim at the detection of this gene defect. In the absence of driver mutations, samples may be tested for associated somatic mutations affecting genes ASXL1, EZH2, TET2, IDH1/2, SRSF2, or SF3B1, among others [1] [5].
• In order to distinguish primary MF from secondary MF, criteria established for the diagnosis of polycythemia vera, essential thrombocytosis, other myeloid neoplasms, and myelodysplastic syndromes should be reviewed. Primary MF is only to be diagnosed if these criteria are not met. Additionally, reactive myelofibrosis developing in the setting of lymphoid or metastatic malignancy, infection, inflammation, or toxic myelopathy should be ruled out [3].
• Minor criteria for the diagnosis of MF comprise anemia, leukocytosis, increased serum lactate dehydrogenase, leukoerythroblastosis (with teardrop-shaped red blood cells), and palpable splenomegaly.

• Nephrolithiasis

  Anxiety Bipolar Depression Obsessive Compulsive Disorder Pediatrics Psychosis Psychosomatic Acute Kidney Injury Chronic Kidney Disease Fluids & Electrolytes Glomerulonephritis Hemodialysis Hypertension REFERENCE BOOK Screening for Hypertension | CTFPHC Nephrolithiasis [qxmd.com]

• Thrombocytosis

  BM Gomori silver impregnation (400×) Primary myelofibrosis, overt fibrosis. 72-year old man, leucocytosis 16×109/L, thrombocytosis 767×109/L, JAK2 unmutated. Intense reticulin fibrosis (MF-2 according to the EUMNET classification). [leukemia-cell.org]

  Myelofibrosis can also occur as a secondary process following the other myeloproliferative disorders (eg, polycythemia vera, essential thrombocytosis). [accessmedicine.mhmedical.com]

  Thrombocytopenia is less frequently observed than thrombocytosis and renders patients prone to bleeding. [symptoma.com]

  Hydroxyurea has traditionally been the preferred and most commonly used agent - moderately effective at improving splenomegaly, leukocytosis and thrombocytosis [ 5 ]. [patient.info]

• Hemoglobin Increased

  Therefore, our recommendation is to carefully monitor young patients with low-risk disease regarding the dynamics and to perform allogeneic SCT if clear signs of progress occur (decrease in hemoglobin, increase in lactate dehydrogenase, constitutional [doi.org]

It is of particular importance to determine the etiology of MF and to adapt the therapeutic regimen to the individual case. Reactive MF may be induced by treatable diseases and tend to have a much better outcome than cases related to myeloproliferative neoplasms [6]. Therapeutic options are limited for patients with primary MF or MF related to other myeloproliferative neoplasms.

JAK 1/2 inhibitor ruxolitinib has received approval for MF treatment in 2012 and continues to be the only drug licensed to this end [7]. Ruxolitinib offers a significant benefit in relieving symptoms and reducing splenomegaly, but there is an inherent risk of worsening cytopenias that requires close monitoring of hematological parameters and possibly pharmacological countermeasures [6]. Danazol, erythroid-stimulating agents, and immunomodulatory drugs may be administered to control ruxolitinib-induced anemia, but the results remain unsatisfactory [7].

Several other JAK inhibitors have been or are currently examined in clinical studies, e.g., fedratinib, pacritinib, momelotinib, and itacitinib. While some have been withdrawn from development due to severe side effects, others have proven to be well tolerated, highly effective, and less myelosuppressive than ruxolitinib [1]. New concepts of MF treatment may be of particular interest to those when ruxolitinib has to be discontinued, as this decision is generally linked to a dismal outcome [7].

To date, hematopoietic stem cell transplantation remains the only curative option. There are comprehensive guidelines concerning patient eligibility, the use of JAK inhibitors before and after the transplantation, conditioning regimens, and donor selection. In general, patients with increased or high-risk disease and age <70 years should be considered potential candidates for stem cell transplantation, while those with intermediate-risk MF and age <65 years should be proposed as candidates only if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood >2%, or adverse cytogenetics [5]. In those with low-risk disease, transplant-related morbidity and mortality outweigh the possible benefits of stem cell transplantation [1]. The respective definitions are part of the International Prognostic Scoring System and its extensions and can be looked up in the literature.

The Dynamic International Prognostic Scoring System is widely used to define the prognosis of an individual patient and considers a total of eight predictors: age >65 years, hemoglobin level <10 g/dl, leukocytes >25*10^9/l, platelet count <100*10^9/l, circulating blasts >1%, constitutional symptoms, transfusion dependency, and unfavorable karyotype [8]. An even better prognostication may be achieved by additionally considering morphological data, most importantly the grade of bone marrow fibrosis [3]. Median survival times of primary MF patients are estimated at 6 years but may range from months to several years, which emphasizes the need for individual assessments [8].

Besides progressive marrow failure and complications from thrombosis, hemorrhages, infections, and portal hypertension, leukemic transformation has been identified as a common cause of death and has, in turn, been related to severe thrombocytopenia and unfavorable karyotypes. In this context, an unfavorable karyotype or platelet count <100*10^9/l may imply a 10-year risk of leukemic transformation of up to 31% [8].

According to the current classification of the World Health Organization, primary MF is a clonal myeloproliferative neoplasm, as are Philadelphia chromosome-positive chronic myeloid leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, polycythemia vera, essential thrombocythemia, and mastocytosis [4]. Secondary MF may develop as a complication of any of these diseases, but is most commonly seen in patients diagnosed with polycythemia vera and essential thrombocythemia.

All these conditions - MF as well as other myeloproliferative neoplasms - have been related to mutations of the JAK2, CALR, and MPL genes. JAK2 mutations are the most common driver mutations in MF patients and are identified in little more than half of all cases, while abnormalities of CALR are determined in less than one-third of the affected individuals. MPL mutations account for less than 10% of MF cases, and a similar share of cases is classified as triple-negative. Other, as-of-yet unknown driver mutations are assumed to trigger MF in these patients [1]. It shall be stressed again that none of these mutations is specific for MF. Just to take the example of JAK2 V617F, which is determined in nearly half of MF cases: This same mutation accounts for a similar percentage of essential thrombocythemia and as much as 90% of cases of polycythemia vera [4].

MF driver mutations eventually alter cytokine release by hematopoietic cells and their precursors. Notwithstanding, cytokines promoting bone marrow fibrosis may originate from non-myeloid cells or iatrogenic sources, which must then be considered as triggers of reactive MF. Kuter and colleagues have compiled an extensive, yet not complete list of conditions associated with increased bone marrow fibrosis [9].

The annual incidence of MF has been estimated at 0.1-1 per 100,000 individuals. Most patients present during their sixth or seventh decade of life, and only about 10% of all cases are diagnosed in individuals aged <40 years [1] [3]. MF in children is increasingly rare but may occur in the setting of germline mutations and familial MF [10]. Regardless of age, males and females are affected equally.

MF is caused by the proliferation of clonal hematopoietic stem cells. Their proliferative advantage over normal cells is conferred by distinct mutations entailing the constitutive activation of the JAK-STAT pathway. This applies to all patients, regardless of whether they carry any of the known driver mutations or are classified as triple-negative [1]. Increased signaling via the JAK-STAT pathway interferes with the regulation of cytokine release and thus contributes to the creation of a proinflammatory and fibrogenic milieu. In detail, vascular endothelial growth factor, transforming growth factor-β, interferon-γ, interleukins 2, 8, and 17, and lipocalin-2 are believed to act in concert to promote the deposition of fibrous connective tissue. At the same time, the population of clonal cells continues to grow, occupying more and more space. Both mechanisms - bone marrow fibrosis and overgrowth of clonal cells - progressively impede polyclonal hematopoiesis and ultimately lead to a state of bone marrow failure and cytopenias [6].

Owing to persisting knowledge gaps regarding the triggers of stem cell degeneration, no recommendations can be given to prevent the onset of primary MF. Concerning MF following essential thrombocythemia and polycythemia vera, novel therapeutics aimed at the prevention of disease progression to myelofibrosis are the focus of current clinical trials [11]. Things look much better with regard to reactive MF: Here, the adequate management of the underlying condition underlying may indeed delay or prevent bone marrow fibrosis.

MF is often used as a synonym of primary MF but is actually a descriptive term referring to the presence of bone marrow fibrosis and extramedullary hematopoiesis [3]. These may be observed in a wide range of diseases, including malignancies, endocrine disorders, autoimmune diseases, and infections, which may or may not originate in the bone marrow [6]. By far the most common variant of MF is primary MF, and the second most important cause of the disease are hematological malignancies. The latter may follow a more aggressive course during their later phases and transform to overt MF. Finally, there's a third group of MF cases that may be classified as reactive bone marrow fibrosis. A number of heterogeneous disorders fall into this category, all of which are uncommon etiologies of bone marrow fibrosis.

Myelofibrosis (MF) denotes the progressive deposition of fibrous tissue in the bone marrow. This condition may have different causes but is most commonly induced by acquired mutations of hematopoietic stem cells, the triggers of which remain unknown. The respective patients are diagnosed with primary MF and are usually of advanced age. Another share of patients suffers from secondary MF, which may be considered an advanced stage of myeloproliferative neoplasms such as essential thrombocythemia and polycythemia vera. Finally, MF may be caused by autoimmune diseases, inflammation, infection, endocrine imbalances, and many other disorders. These patients account for a very small share of MF cases, though.

Both the overgrowth of mutated cells and progressive bone marrow fibrosis interfere with the formation of new, healthy blood cells. MF patients may thus present with distinct hematological abnormalities, such as increased or decreased counts of red blood cells, white blood cells, and platelets. They may claim fatigue and weakness due to anemia, be predisposed to infections, thrombosis, or bleeding. As the body tries to compensate for bone marrow failure, hematopoiesis is stimulated elsewhere, entailing the enlargement of liver and spleen.

None of these symptoms is specific for MF, and a thorough workup is required to diagnose this disease and to identify possible causes. Both treatment and prognosis largely depend on many factors, e.g., the age of the patient, the presence of comorbidities, the stage of the disease and the precise mutations underlying MF. The median survival of patients diagnosed with primary MF, the most common form of the disease, has been estimated at 6 years but may range from months to several years.

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3. Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 4ed. Lyon, France: IARC Press; 2017.
4. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5):937-951.
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8. Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011; 29(4):392-397.
9. Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol. 2007; 139(3):351-362.
10. Sieff CA, Malleson P. Familial myelofibrosis. Arch Dis Child. 1980; 55(11):888-893.
11. Aruch D, Mascarenhas J. Contemporary approach to essential thrombocythemia and polycythemia vera. Curr Opin Hematol. 2016; 23(2):150-160.