慢性骨髓單核球性白血病

Buzzwords → Dx

Diagnostic Criteria (WHO 5e / ICC 2022)

• Persistent monocytosis ≥1 × 10⁹/L AND monocytes ≥10 % of WBC for ≥3 months.
• Marrow blasts <20 % (≥20 % = AML).
• One or more clonal cytogenetic/molecular abnormality OR ≥10 % dysplasia in ≥1 lineage.
• Exclude: CML BCR::ABL1, atypical CML, juvenile MML (children), other myeloid neoplasms, FIP1L1::PDGFRA hyper-eosinophilic syndrome, reactive monocytosis (chronic infection, autoimmune).
• CMML subtypes: CMML-1 (blasts <5 %), CMML-2 (blasts 5–19 % marrow or 5–19 % blood with promyelocytes/myelocytes counted as blasts).
• Phenotype: "MPN-CMML" (WBC ≥13 × 10⁹/L) vs "MDS-CMML" (WBC <13 × 10⁹/L).

Workup

• Persistent ≥3-mo monocytosis documented; rule out reactive causes (infection, autoimmune, splenectomy, malignancy).
• Smear: monocytic series, dysplasia of granulocytic and erythroid lines.
• BCR::ABL1 PCR/FISH to rule out CML.
• JAK2/CALR/MPL to rule out MPN.
• PDGFRA/PDGFRB/FGFR1 rearrangements if hyper-eosinophilic — these are imatinib-treatable (FIP1L1::PDGFRA).
• Marrow: cytogenetics + NGS panel (TET2, SRSF2, ASXL1, NRAS, KRAS, CBL, RUNX1, JAK2, EZH2, etc.).
• Spleen size by exam/imaging.
• HLA typing if HCT candidate.

Treatment Algorithm (CPSS-Mol risk)

flowchart TD
  A[Confirmed CMML] --> B[CPSS-Mol risk<br>blasts, WBC, RBC tx, ASXL1, NRAS, RUNX1, SETBP1]
  B -- low / int-1 --> C{Symptomatic?}
  C -- no --> D[Observation]
  C -- yes anemia --> E[ESA if EPO <500<br>or HMA / lenalidomide]
  C -- yes splenomegaly/<br>proliferation --> F[Hydroxyurea<br>or HMA]
  B -- int-2 / high --> G{Fit for allo-HCT?}
  G -- yes --> H[HMA azacitidine bridge → Allo-HCT in CR<br>= only cure]
  G -- no --> I[Azacitidine or<br>aza + venetoclax<br>or oral decitabine + cedazuridine]
  H --> J{Relapse / progression?}
  I --> J
  J -- AML transformation --> K[Treat as MDS-related AML]

Pearls / Pitfalls

• CMML is MDS/MPN overlap, NOT a subtype of MDS — IPSS-R/IPSS-M not validated for CMML; use CPSS-Mol instead.
• TET2 + SRSF2 co-mutation is highly specific for CMML — even with monocyte percentages just below the 10 % threshold, this combination supports the diagnosis.
• PDGFRA-rearranged hyper-eosinophilic syndrome (FIP1L1::PDGFRA fusion at 4q12) mimics CMML with eosinophilia but is imatinib-curative — do not miss; PDGFRB and FGFR1 are similar.
• MPN-CMML phenotype (WBC >13 × 10⁹/L, splenomegaly, NRAS/KRAS) → hydroxyurea for cytoreduction, then HMA if symptomatic / progressive.
• Allo-HCT is the only curative therapy — pursue early in fit, higher-risk pts; HMA bridges as needed.
• HMA durability is short in CMML; CR rates ~10–20 %; OS gains modest. Don't promise prolonged remission with HMA monotherapy.
• JMML (juvenile myelomonocytic leukemia, children) is a distinct entity (PTPN11, NRAS, KRAS, CBL, NF1) — pediatric, allo-HCT-driven.
• CMML can transform to AML (~20–30 %); AML transformation predicted by CPSS-Mol high-risk + ≥2 cytogenetic abnormalities.

Cross-references

• MDS — distinguishing MDS-CMML
• Cytogenetics Atlas — TET2, SRSF2, ASXL1, NRAS
• Drug Regimens — azacitidine, hydroxyurea, oral decitabine
• Allogeneic HCT — only cure

相關題目

• Q-032 — CMML — diagnostic criteria
• Q-033 — CMML — eosinophilia mimic and FIP1L1::PDGFRA
• Q-034 — CMML — risk stratification (CPSS-Mol, not IPSS-M)

Sources