慢性骨髓性白血病

Buzzwords → Dx

Diagnostic Criteria

• Confirmation: BCR::ABL1 RT-PCR (sensitive, transcript IS quantification) ± karyotype t(9;22) + FISH for fusion.
• Phase definition (WHO 5e / ELN-2020):
  • Chronic phase (CP): blasts <10 % marrow/blood
  • Accelerated phase (AP): blasts 10–19 %, basophils ≥20 %, persistent thrombocytopenia, additional cytogenetics, KMT2A or other clonal evolution
  • Blast phase (BP): ≥20 % blasts (myeloid or lymphoid lineage)
• Atypical CML (BCR::ABL-negative) is a separate WHO-MDS/MPN entity (NOT CML; treat as MDS/MPN).
• Major molecular response (MMR/MR3) = BCR::ABL1 IS ≤0.1 %. Deep responses: MR4 ≤0.01 %, MR4.5 ≤0.0032 %, MR5 ≤0.001 %.

Workup

• CBC + diff + manual smear (basophilia, left shift, occasional blasts).
• Marrow — confirm phase, cytogenetics + FISH, NGS if AP/BP.
• Quant BCR::ABL1 RT-PCR (IS) baseline.
• HLA typing only if AP/BP or anticipated allo-HCT.
• Cardiac risk before nilotinib/ponatinib (vasospastic / arterial events).
• TLS prophylaxis if very high WBC at diagnosis (rare leukostasis).

Treatment Algorithm

flowchart TD
  A[Newly diagnosed CML-CP] --> B[ELTS / Sokal score]
  B --> C{First-line TKI choice}
  C -- low-risk, comorbid --> D[Imatinib 400 mg]
  C -- high-risk or rapid response goal<br>or planning TFR --> E[2G-TKI<br>dasatinib / nilotinib / bosutinib]
  C --> M{Cardiovascular risk?}
  M -- high --> N[Avoid nilotinib/ponatinib<br>imatinib or bosutinib preferred]
  D --> F[BCR::ABL1 IS at 3 / 6 / 12 mo]
  E --> F
  F -- meets milestones --> G[Continue; aim MR4 + ≥2 yr → TFR candidate]
  F -- not meeting --> H[Mutation analysis<br>switch TKI]
  H -- T315I --> I[Ponatinib or asciminib]
  H -- other resistance --> J[Switch to alternate 2G/3G TKI]
  I --> K{Failure to 2 lines or AP/BP?}
  J --> K
  K -- yes --> L[Allo-HCT consideration]
  G --> O{TFR attempt criteria?<br>CP only, MR4 ≥2 yr, no AP/BP hx}
  O -- yes --> P[Stop TKI, monitor monthly × 6 mo<br>then q3 mo<br>resume if MR3 lost]

Pearls / Pitfalls

• TFR criteria (NCCN): CP only (no AP/BP history), typical e13a2/e14a2 transcripts, MR4 sustained ≥2 yr (or MR4.5 ≥2 yr per some guidelines), high-quality qPCR lab, monthly monitoring × 6 mo then q3 mo. Loss of MMR (>0.1 %) → resume TKI.¹
• T315I gatekeeper mutation = ponatinib or asciminib only. Imatinib, dasatinib, nilotinib, bosutinib all ineffective. Ponatinib has highest arterial/vascular event rate — careful CV screening.
• Nilotinib & ponatinib → arterial events (PAOD, MI, stroke); dasatinib → pleural effusion + pulmonary HTN; bosutinib → diarrhea + hepatotoxicity; imatinib → edema/cytopenias. Match TKI to comorbidity.
• Compound BCR-ABL1 mutations (e.g., T315I + other) can be resistant to ponatinib → consider asciminib or allo-HCT.
• No drug-drug interaction reminder: TKIs metabolized by CYP3A4. Avoid strong inhibitors (azole antifungals, clarithromycin) + grapefruit. PPI use lowers dasatinib/bosutinib absorption.
• Aspirin in CML has no role; CML coagulopathy is rare. Don't confuse with PV/ET thrombosis prophylaxis.
• Pregnancy: TKIs are teratogenic (especially imatinib in 1st trimester); switch to interferon during pregnancy or hold + monitor.

Cross-references

• Cytogenetics Atlas — t(9;22), T315I
• Drug Regimens — TKIs (imatinib/dasatinib/etc.), ponatinib, asciminib
• Ph+ ALL — TKI overlap
• PV — JAK2-driven MPN contrast

相關題目

• Q-011 — CML — TKI choice in patient with cardiovascular comorbidities
• Q-012 — CML — T315I gatekeeper mutation
• Q-013 — CML — Treatment-Free Remission (TFR) eligibility

Sources