原發性骨髓纖維化

Buzzwords → Dx

Diagnostic Criteria (WHO 5e)

Major (all 3):

1. Megakaryocytic proliferation + atypia, accompanied by reticulin and/or collagen fibrosis (grade 2 or 3 in overt-PMF; ≤grade 1 in pre-PMF).
2. Not meeting WHO criteria for ET, PV, BCR::ABL+ CML, MDS, or other myeloid neoplasm.
3. JAK2, CALR, or MPL mutation OR (in their absence) another clonal marker OR no evidence of reactive marrow fibrosis.

Minor (≥1):

• Anemia not from comorbidity, leukocytosis ≥11, splenomegaly, ↑LDH, leukoerythroblastosis.

Workup

• CBC + smear (dacrocytes, NRBC, immature granulocytes), LDH, CMP, uric acid.
• JAK2 / CALR / MPL mutation testing (sequential or panel).
• Marrow biopsy + reticulin staining (key — assess MF-grade); karyotype + NGS panel (HMR).
• Spleen size by exam/US/CT.
• HLA typing if HCT candidate.
• Performance status / frailty for JAKi vs HCT decisions.

Treatment Algorithm

flowchart TD
  A[Confirmed PMF] --> B[Risk stratification<br>DIPSS-Plus or MIPSS70+ v2.0]
  B -- low / int-1 --> C{Symptomatic?}
  C -- no --> D[Observation; ESA if anemia<br>aspirin if thrombosis risk]
  C -- yes splenomegaly/symptoms --> E[Ruxolitinib]
  B -- int-2 / high --> F{Fit for allo-HCT?}
  F -- yes --> G[Allo-HCT preceded by JAKi to reduce spleen size<br>= only cure]
  F -- no --> H{Predominant feature?}
  H -- splenomegaly + symptoms + plt >50 --> I[Ruxolitinib<br>or fedratinib if 2L]
  H -- thrombocytopenia plt <50 --> J[Pacritinib]
  H -- significant anemia --> K[Momelotinib<br>preferred — SIMPLIFY-2]
  E --> L{Progression / loss of response?}
  I --> L
  J --> L
  K --> L
  L -- yes --> M[Switch JAKi class<br>or transfusion / supportive<br>or palliative spleen RT/embolization]

Pearls / Pitfalls

• Ruxolitinib withdrawal syndrome — abrupt discontinuation can cause cytokine rebound, fever, hypotension, even death. Taper, don't stop.
• Fedratinib → Wernicke-like encephalopathy (thiamine depletion). Check thiamine baseline + supplement.
• Pacritinib is platelet-sparing → preferred when plt 50–100 or even <50. JAK2/FLT3/IRAK1 inhibitor.
• Momelotinib (JAK1/JAK2/ACVR1 inhibitor) → improves anemia (suppresses hepcidin via ACVR1) — preferred when anemia is dominant (SIMPLIFY-2 / MOMENTUM).
• Pre-PMF is NOT ET — same threshold for plt but worse outcomes. Reticulin staining + meg morphology distinguishes. Treat as PMF if MF-1 fibrosis present.
• Triple-negative PMF (no JAK2/CALR/MPL) = worst prognosis — early HCT consideration.
• CALR type 1 ≫ JAK2 V617F ≫ CALR type 2 ≫ MPL ≫ triple-negative (best→worst PMF prognosis).
• Splenectomy is a last resort (high perioperative mortality, post-splenectomy hepatic engorgement, leukocytosis); spleen RT (low-dose) + embolization sometimes used.
• EPO levels >500 predict ESA failure — switch to luspatercept (data emerging in MF) or transfusion + iron chelation.
• Post-PV/post-ET MF (secondary MF, SMF): behaves like PMF; risk-stratify with MYSEC-PM (post-PV/ET-specific score).

Cross-references

• Cytogenetics Atlas — JAK2, CALR, MPL
• Staging — DIPSS-Plus, MIPSS70+, MYSEC-PM
• Drug Regimens — JAK inhibitors
• PV — post-PV MF
• ET — post-ET MF, pre-PMF DDx
• Allo-HCT — only cure
• Iron chelation in transfusion-dependent MF

相關題目

• Q-029 — PMF — JAK inhibitor selection in anemia-dominant disease
• Q-030 — PMF — fedratinib and Wernicke encephalopathy
• Q-031 — PMF — ruxolitinib withdrawal syndrome

Sources