What is myelofibrosis (bone marrow fibrosis)?

From the Guidelines

Myelofibrosis is a rare bone marrow cancer characterized by the presence of megakaryocyte proliferation and atypia, accompanied by reticulin and/or collagen fibrosis, and is diagnosed based on the revised WHO criteria, which requires meeting all 3 major criteria and 2 minor criteria, as outlined in the study by 1.

Definition and Diagnosis

Myelofibrosis belongs to a group of blood disorders called myeloproliferative neoplasms, where the bone marrow gradually becomes scarred and fibrous, preventing it from making enough healthy blood cells. The diagnosis of myelofibrosis is based on the presence of megakaryocyte proliferation and atypia, accompanied by reticulin and/or collagen fibrosis, and the absence of other myeloid neoplasms, as stated in the study by 1. The revised WHO criteria for primary myelofibrosis require meeting all 3 major criteria and 2 minor criteria, which include:

• Major criteria:
  • Presence of megakaryocyte proliferation and atypia
  • Not meeting WHO criteria for PV, CML, MDS, or other myeloid neoplasm
  • Demonstration of JAK2V617F or other clonal marker
• Minor criteria:
  • Leukoerythroblastosis
  • Increase in serum lactate dehydrogenase level
  • Anemia
  • Palpable splenomegaly

Treatment and Management

Treatment of myelofibrosis depends on symptom severity and may include medication like ruxolitinib (Jakafi) to reduce inflammation and spleen size, hydroxyurea to control blood cell counts, corticosteroids for inflammation, blood transfusions for anemia, and radiation for bone pain, as recommended in the study by 1. For eligible patients, stem cell transplantation offers the only potential cure but carries significant risks, as stated in the study by 1. The selection of patients for allogeneic HCT should be based on age, performance status, major comorbid conditions, psychosocial status, patient preference, and availability of caregiver, as outlined in the study by 1.

Prognosis and Complications

Without treatment, complications of myelofibrosis can include severe anemia, bleeding problems, increased infection risk, portal hypertension, and transformation to acute leukemia in some cases, as mentioned in the study by 1. The dynamic international prognostic scoring system (DIPSS)-Plus is preferred for the risk stratification of myelofibrosis, and identification of "higher-risk" mutations may be helpful in the decision-making regarding allogeneic HCT, as stated in the study by 1.

From the Research

Definition of Myelofibrosis

Myelofibrosis (MF) is characterized by:

• Bone marrow fibrosis
• Progressive anemia
• Extramedullary hematopoiesis, primarily manifested as splenomegaly
• Debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats, and fatigue 2, 3, 4, 5, 6

Clinical Hallmarks

The clinical hallmarks of myelofibrosis include:

• Splenomegaly
• Anemia
• Debilitating symptoms 3, 5, 6

Pathophysiology

Myelofibrosis is a BCR-ABL1-negative myeloproliferative neoplasm, with constitutive activation of the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, leading to:

• Myeloproliferation
• Proinflammatory cytokine expression
• Bone marrow remodeling 3

Disease Characteristics

Myelofibrosis is a chronic myeloproliferative neoplasm, with patients at risk for:

• Reduced survival
• Burdensome signs and symptoms that reduce quality of life 4
• Life-threatening complications, including transformation to leukemia, thrombotic events, and hemorrhagic episodes 6