Agnogenic myeloid metaplasia (Myelofibrosis)

Agnogenic Myeloid Metaplasia (Myelofibrosis) – Treatment Options

Introduction
Agnogenic myeloid metaplasia, more commonly referred to as primary myelofibrosis (PMF), is a chronic myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly. Patients may present with anemia, constitutional symptoms (fatigue, weight loss, night sweats, fever), bone pain, and complications from splenic enlargement. The disease course is variable, ranging from indolent to rapidly progressive, and may evolve into acute myeloid leukemia (AML). Management focuses on symptom control, improving quality of life, and prolonging survival, with therapy tailored to risk stratification.

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1. Supportive Care

• Transfusions:

  • Red blood cell transfusions for symptomatic anemia.

  • Platelet transfusions if severe thrombocytopenia with bleeding.

• Erythropoiesis-stimulating agents (ESAs): May benefit some anemic patients with low serum erythropoietin levels.

• Androgens (danazol), corticosteroids, or thalidomide/lenalidomide: Sometimes used to improve anemia.

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2. JAK Inhibitors (Targeted Therapy)

• Ruxolitinib (JAK1/JAK2 inhibitor):

  • Improves splenomegaly, constitutional symptoms, and quality of life.

  • Used in intermediate- and high-risk patients.

• Fedratinib (JAK2 inhibitor):

  • Approved for patients intolerant of or resistant to ruxolitinib.

• Other JAK inhibitors (momelotinib, pacritinib) are emerging for patients with cytopenias or ruxolitinib resistance.

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3. Cytoreductive Therapy

• Hydroxyurea:

  • Reduces leukocytosis, thrombocytosis, and splenomegaly.

  • Used in patients not eligible for JAK inhibitors or with proliferative features.

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4. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

• The only potentially curative option.

• Recommended for younger, fit patients with high-risk or advanced disease.

• Carries significant morbidity and mortality, so careful patient selection is essential.

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5. Splenectomy and Splenic Irradiation

• Splenectomy:

  • Considered for refractory splenomegaly causing pain, cytopenias, or portal hypertension.

  • Risks: bleeding, infection, thrombosis, accelerated hepatomegaly, transformation to acute leukemia.

• Splenic irradiation:

  • Palliative option for patients not suitable for surgery; effect is temporary and associated with cytopenias.

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6. Experimental and Adjunctive Therapies

• Clinical trials: Investigating novel agents targeting fibrosis, telomerase, hedgehog pathway, and epigenetic regulators.

• Interferon-alpha: Sometimes used in early disease, though less effective in advanced fibrosis.

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7. Long-Term Supportive Measures

• Symptom management: Analgesics for bone pain, antihistamines for pruritus.

• Infection prevention: Vaccinations, prophylactic antibiotics in selected patients.

• Regular monitoring: Blood counts, spleen size, and assessment for leukemic transformation.