骨髓化生不良症候群

Buzzwords → Dx

Diagnostic Criteria

• WHO 5e / ICC 2022: clonal cytopenia(s) ± dysplasia ± excess blasts; minimum dysplasia ≥10 % in ≥1 lineage OR cytogenetic clue.
• Cytopenia thresholds: Hb <13 (M) / <12 (F), ANC <1.8 × 10⁹/L, plt <150 × 10⁹/L (CCUS uses these but no dysplasia/cytogenetics).
• CHIP / CCUS: clonal hematopoiesis with cytopenia (CCUS) or without (CHIP) — not yet MDS.
• MDS-defining genetic abnormalities (5e): SF3B1, biallelic TP53, isolated del(5q) — diagnose at lower dysplasia thresholds.
• MDS/AML (ICC) or MDS-IB2 (WHO): 10–19 % marrow blasts.
• AML threshold: ≥20 % blasts (most contexts) or recurrent genetic abnormality.

Workup

• CBC + diff + retic + smear, B12/folate, ferritin, EPO (if anemic, EPO <500 mU/mL predicts ESA response).
• Bone marrow aspirate + biopsy with iron stain (ringed sideroblasts), karyotype + FISH (–5/del(5q), –7/del(7q), del(20q), trisomy 8, del(17p)), NGS panel ≥30 genes.
• HLA typing if allo-HCT candidate.
• PNH flow (CD55/CD59) if hypocellular marrow.
• Iron studies (transfusion burden).

Treatment Algorithm

flowchart TD
  A[Confirmed MDS] --> B[IPSS-M risk stratification]
  B -- Very low / Low --> C{Symptomatic?}
  C -- no --> D[Observation, support]
  C -- yes anemia --> E{del(5q)?}
  E -- yes --> F[Lenalidomide]
  E -- no --> G{EPO < 500 ?}
  G -- yes --> H[ESA ± G-CSF]
  G -- no --> I{Ringed sideroblasts<br>or SF3B1?}
  I -- yes --> J[Luspatercept<br>COMMANDS first-line]
  I -- no --> K[Luspatercept or HMA]
  B -- Mod-low / Moderate --> L[ESA / luspatercept / lenalidomide if del(5q)<br>+ early HCT consult]
  B -- Mod-high / High / Very high --> M{Fit for allo-HCT?}
  M -- yes --> N[Azacitidine bridge → Allo-HCT in CR]
  M -- no --> O[Azacitidine ± Venetoclax<br>or + IDH1i/IDH2i if mutated]
  L --> P{Progression?}
  N --> P
  O --> P
  P --> Q[Re-evaluate IPSS-M; HCT in CR is curative path]

Pearls / Pitfalls

• IPSS-M uses 31 mutations. TP53^multi-hit^ is the dominant adverse driver, even outweighing complex karyotype. Picking IPSS-R when IPSS-M is available is the wrong answer.²
• Luspatercept (COMMANDS) is now first-line for transfusion-dependent low-risk MDS with ringed sideroblasts/SF3B1, beating ESAs. Don't default to "always start with EPO."³
• Lenalidomide is for isolated del(5q), not for non-del(5q) anemia. Use only if isolated del(5q) (or del(5q) + 1 other non-7).
• Azacitidine in low-risk MDS: oral aza (CC-486) is the only formulation studied for MDS maintenance / lower-risk in selected settings. IV/SC azacitidine remains the standard for higher-risk MDS.
• IDH1 (ivosidenib) and IDH2 (enasidenib) inhibitors are now FDA-approved for relapsed/refractory IDH-mutated MDS (and AML); ivosidenib + azacitidine has data in MDS.
• Allogeneic HCT in CR1 is the only curative option — even in older fit pts. Don't delay HLA typing in higher-risk MDS.
• TLS risk is low in MDS at HMA initiation but rises if cytoreduction is rapid; aza ± venetoclax can cause TLS in high-blast MDS.
• TP53-mutated MDS has poor HMA durability (median CR ~5–7 mo). Clinical trials (eprenetapopt, magrolimab pre-discontinuation, etc.) historically prioritized; current standard = aza ± Ven + early HCT.
• CMML is NOT classified as MDS — separate MDS/MPN entity (see CMML). Rule out by monocyte count (>1 × 10⁹/L AND ≥10 % differential).
• Hypoplastic MDS: overlaps with aplastic anemia. Search for PNH clone; immunosuppression (ATG + cyclosporine) sometimes used in young pts.

Cross-references

• Cytogenetics Atlas — del(5q), –7, TP53
• WHO/ICC 2022 — MDS subtypes
• Staging — IPSS-R, IPSS-M
• CMML — MDS/MPN overlap
• AML — MDS/AML overlap entity (ICC)
• Aplastic anemia — hypocellular MDS DDx
• PNH — DDx in hypocellular marrow

相關題目

• Q-020 — MDS — IPSS-M risk stratification
• Q-021 — MDS — luspatercept first-line for SF3B1+ lower-risk
• Q-022 — MDS — higher-risk treatment in HCT-eligible patient
• Q-143 — CHIP — clonal hematopoiesis of indeterminate potential
• Q-201 — ESA — EPO level threshold in MDS
• Q-210 — Iron chelation in lower-risk MDS (TELESTO)

Sources