What is the initial treatment for a 55-year-old female with primary myelofibrosis (bone marrow disorder) in the fibrotic stage?

Initial Treatment for Primary Myelofibrosis in a 55-Year-Old Female

For a 55-year-old woman with primary myelofibrosis in the fibrotic stage, risk stratification using IPSS or DIPSS must be performed immediately to determine whether allogeneic hematopoietic stem cell transplantation (AHSCT) or JAK inhibitor therapy is the appropriate initial treatment. 1

Risk Stratification Determines Treatment Path

The first critical step is calculating the patient's risk category using the International Prognostic Scoring System (IPSS) at diagnosis or Dynamic IPSS (DIPSS) at any time during disease course 1. This determines whether curative or palliative therapy is appropriate.

For Intermediate-2 or High-Risk Disease

• AHSCT should be pursued as the initial treatment for transplant-eligible patients with intermediate-2 or high-risk disease, as this is the only curative option with cure rates of 40-70%, despite 30% treatment-related mortality at 1 year 1
• AHSCT is justified when median survival is expected to be less than 5 years, which includes these risk categories 1
• At age 55, this patient is within the transplant-eligible age range (typically <65 years) 1

For Intermediate-1 Risk Disease

• Selected patients younger than 65 years with intermediate-1 risk who have poor-risk features and median survival less than 5 years should also be considered for AHSCT 1
• Poor-risk features include constitutional symptoms, progressive splenomegaly, transfusion-dependent anemia, or high-risk molecular mutations 2

For Low-Risk Disease or Non-Transplant Candidates

Ruxolitinib is the first-line pharmacologic therapy for symptomatic myelofibrosis in patients who are not transplant candidates 1, 3. This JAK1/2 inhibitor:

• Achieves 35% spleen volume reduction and improves overall survival in intermediate-2 and high-risk patients 1
• Improves survival compared to placebo and best available therapy, regardless of JAK2 mutational status 1
• Is effective but not curative, with limited disease-modifying effects 1

Symptom-Directed Management Alongside Primary Therapy

Anemia (Hemoglobin <10 g/dL)

Initiate treatment with one of the following first-line options 4, 1:

• Corticosteroids (0.5-1.0 mg/kg/day) with 30-40% response rate 4
• Androgens (testosterone enanthate 400-600 mg weekly or oral fluoxymesterone 10 mg three times daily) with 30-40% response rate 4
• Danazol 600 mg/day with 30-40% response rate 4
• Lenalidomide is preferred if del(5q) is present 4, 1

Symptomatic Splenomegaly

• Hydroxyurea is the drug of choice, achieving approximately 40% spleen volume reduction 4, 1
• Alternative myelosuppressive agents for hydroxyurea-refractory disease include intravenous cladribine (5 mg/m²/day for 5 consecutive days, repeated monthly for 4-6 cycles), oral melphalan (2.5 mg three times weekly), or oral busulfan (2-6 mg/day with close blood count monitoring) 4

Thrombosis Prevention

• Low-dose aspirin (81-100 mg daily) should be initiated for all patients without contraindications 1, 5
• Cytoreductive therapy (hydroxyurea for older patients; interferon for younger patients or those of childbearing age) controls myeloproliferation and reduces thrombotic risk 1, 5

Ruxolitinib Dosing and Monitoring (If Applicable)

Initial dosing is based on baseline platelet count 3, 6:

• Platelets ≥200 × 10⁹/L: Start 20 mg twice daily
• Platelets 100-200 × 10⁹/L: Start 15 mg twice daily
• Platelets 50-100 × 10⁹/L: Start 5 mg twice daily

For anemic patients, start with 10 mg twice daily for 12 weeks and consider erythropoiesis-stimulating agents if endogenous erythropoietin levels ≤500 mU/mL 6.

Key Adverse Effects to Monitor

• Thrombocytopenia and worsening anemia occur especially early in therapy 1
• Increased infection risk requires vigilance for opportunistic infections 6
• Second primary malignancies require increased surveillance 6

Critical Pitfalls to Avoid

• Do not delay risk stratification—treatment intensity depends entirely on IPSS/DIPSS category, and AHSCT should not be deferred in eligible high-risk patients 1
• Do not assume ruxolitinib is disease-modifying—it provides symptom control and survival benefit but is not curative; only AHSCT offers cure 1, 7
• Do not abruptly discontinue ruxolitinib—progressive dose tapering is recommended when stopping to avoid withdrawal symptoms 6
• Do not overlook splenectomy indications—consider for symptomatic portal hypertension, drug-refractory marked splenomegaly, or established transfusion-dependent anemia, though perioperative mortality is 5-10% with complications in approximately 50% of patients 1

Monitoring Schedule

• Complete blood counts every 3-6 months or more frequently as clinically indicated 4
• Assess for new thrombotic or bleeding events 4
• Monitor spleen size, serum lactate dehydrogenase, and disease-related symptoms 4
• Post-AHSCT patients should have JAK2V617F allele burden monitored to predict relapse 1