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Myelofibrosis

Chronic myeloproliferative neoplasm with bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, and constitutional symptoms.

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

This content is for informational purposes only and does not constitute medical advice. You can book an appointment at our Hematoloji department. Book Appointment →

What is Myelofibrosis?

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (MPN), occurring as primary myelofibrosis (PMF) or secondary to polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF). Driver mutations include JAK2 V617F (60%), CALR (20-25%), and MPL (5-10%); about 10% are triple-negative. Disease arises from hematopoietic stem cell clonal proliferation with cytokine-driven reactive bone marrow fibrosis (TGF-beta, FGF, PDGF), megakaryocyte atypia, and progressive marrow failure with extramedullary hematopoiesis (especially splenic and hepatic).

Clinical features include progressive anemia, splenomegaly (often massive), constitutional symptoms (weight loss, night sweats, fatigue), bone pain, pruritus, splenic infarcts, and signs of portal hypertension. Risk of thrombosis is increased; transformation to acute myeloid leukemia occurs in 10-20%. Diagnosis combines peripheral smear (leukoerythroblastic blood with teardrop red cells), bone marrow biopsy with reticulin/collagen fibrosis grading, JAK2/CALR/MPL mutation testing, and exclusion of other MPNs and reactive causes.

Risk stratification (DIPSS, DIPSS-Plus, MIPSS70+ v2.0) integrates age, hemoglobin, white count, blasts, constitutional symptoms, karyotype, and high-molecular-risk mutations (ASXL1, EZH2, IDH1/2, SRSF2). Therapy is risk-adapted: observation in low-risk asymptomatic, JAK inhibitors (ruxolitinib first-line; fedratinib, momelotinib, pacritinib in select scenarios) for symptomatic disease, supportive care for anemia and cytopenias, and allogeneic stem cell transplant in eligible higher-risk patients as the only curative option.

Symptoms

Fatigue, weakness
Splenomegaly (often massive, left upper quadrant fullness)
Hepatomegaly
Anemia symptoms (pallor, dyspnea)
Weight loss, anorexia
Night sweats
Bone pain
Pruritus, especially after warm shower
Early satiety, abdominal discomfort
Splenic infarction (acute left upper quadrant pain)
Portal hypertension, ascites, varices
Bleeding, easy bruising (thrombocytopenia)
Recurrent infections (leukopenia)
Gout, hyperuricemia
Leukoerythroblastic blood film, teardrop red cells
Acute leukemia transformation (rapid blast increase)
Pulmonary hypertension

Risk Factors

JAK2 V617F mutation
CALR exon 9 mutations
MPL W515 mutations
High-molecular-risk mutations: ASXL1, EZH2, IDH1/2, SRSF2
Older age
Prior polycythemia vera or essential thrombocythemia (secondary MF)
Cytogenetic abnormalities (complex, monosomal karyotype, del(17p))
Bone marrow fibrosis grade 2-3
Constitutional symptoms
High blast count, anemia, leukocytosis
Splenomegaly size
Family history of MPN (rare)
Radiation, benzene exposure (occupational)
Thrombosis, bleeding history
Iron overload from transfusions

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Persistent unexplained anemia or pancytopenia
  • Splenomegaly with constitutional symptoms
  • Bone pain with night sweats and weight loss
  • Known PV or ET with new anemia or splenomegaly
  • Pruritus with hematologic abnormalities
  • Sudden severe left upper quadrant pain (splenic infarct)
  • Rapidly rising blast count (leukemic transformation)
  • Bleeding, infection, or thrombosis in known MF
  • Pre-transplant assessment in eligible patients

Treatment Methods

01
Hematology referral for evaluation
02
CBC, peripheral smear (leukoerythroblastic, teardrop cells), reticulocyte count
03
LDH, uric acid, comprehensive metabolic panel
04
JAK2 V617F, CALR exon 9, MPL W515 mutation testing; expanded NGS panel for high-molecular-risk mutations
05
Bone marrow aspiration and biopsy with reticulin and trichrome staining for fibrosis grade
06
Karyotype and FISH
07
BCR-ABL1 to exclude CML
08
Imaging: abdominal ultrasound or CT for splenomegaly and portal hypertension
09
Risk stratification: DIPSS, DIPSS-Plus, MIPSS70+ v2.0, MYSEC-PM (post-PV/ET MF)
10
Low-risk asymptomatic: observation, address symptoms
11
Symptomatic disease (constitutional symptoms, splenomegaly): JAK inhibitor — ruxolitinib first-line; fedratinib for ruxolitinib failure; momelotinib for anemia-predominant; pacritinib for severe thrombocytopenia
12
Anemia: erythropoiesis-stimulating agents, danazol, lenalidomide (in some cases), thalidomide-like agents, transfusion support, iron chelation if overload
13
Splenomegaly: JAK inhibitor; splenectomy or splenic radiation in selected refractory cases
14
Constitutional symptoms: JAK inhibitor primary; supportive measures
15
Leukemic transformation: AML-directed therapy, urgent transplant consideration
16
Allogeneic hematopoietic stem cell transplant: intermediate-2 or high-risk patients fit for transplant — only curative option
17
Hydration, allopurinol for hyperuricemia
18
Vaccinations (pneumococcal, influenza, COVID), avoid live vaccines on JAK inhibitor
19
Patient education on infection signs, bleeding, thrombosis, drug interactions
20
Multidisciplinary care: hematology, transplant team, hepatology, palliative care if advanced
21
Long-term monitoring: CBC, blasts, splenomegaly, mutation burden, transplant readiness

Which Department to Visit?

You can visit our Hematoloji department for these complaints. Our specialist physicians will create the most suitable treatment plan for you.

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Health Disclaimer: The information on this page is prepared for general informational purposes only. It does not replace medical diagnosis and treatment. Please consult your physician for your complaints. Saygı Hospital does not accept responsibility for actions taken based on the information on this page.