AL 型類澱粉沉積症

Buzzwords → Dx

Diagnostic Criteria

1. Tissue biopsy with Congo red apple-green birefringence (fat-pad, abdominal fat aspirate, organ biopsy).
2. Subtype confirmation by mass spec or IHC — AL (vs ATTR-wild-type, ATTR-mutant, AA).
3. Demonstration of clonal plasma cell dyscrasia (sFLC ratio + SPE/IFE + marrow with FISH).
4. Organ involvement documented (cardiac, renal, hepatic, neurologic, GI, soft tissue).

Workup

• Fat-pad aspirate (~70–80 % sensitive) → if negative + high suspicion → organ biopsy.
• Congo red + immunoelectron microscopy / mass spectrometry for subtype.
• NT-proBNP, troponin (T or I), creatinine, eGFR, 24-hr urine protein, alkaline phosphatase.
• Echo + cardiac MRI (LGE pattern), ECG (low voltage).
• sFLC + SPE + IFE + UPE/UIFE + marrow with FISH (t(11;14) common in AL — bortezomib- or venetoclax-sensitive).
• Mayo 2012 staging:
  • Stage I: NT-proBNP <332 pg/mL AND troponin T <0.025 ng/mL
  • Stage II: one of those elevated
  • Stage III: both elevated
  • Stage IV (Mayo 2012 Eur revision): IIIb if NT-proBNP >8500 pg/mL — very high mortality
• Coagulation panel (factor X, PT, aPTT) for bleeding risk.

Treatment Algorithm

flowchart TD
  A[Confirmed AL amyloid] --> B[Mayo 2012 cardiac stage I-IV]
  B --> C{Stage IV / Eur IIIb?}
  C -- yes --> D[Lower-intensity Dara + CyBorD<br>or palliative; auto-HCT excluded]
  C -- no --> E{Auto-HCT eligible?<br>NYHA I-II, EF >40 %, eGFR >30,<br>SBP >90, PS good}
  E -- yes --> F[Induction Dara-CyBorD × 4-6<br>then auto-HCT consolidation]
  E -- no --> G[Dara-CyBorD × 6-9 cycles<br>continuous]
  F --> H[Hematologic response: dFLC <10 or normal ratio = CR]
  G --> H
  H --> I[Cardiac response<br>≥30 % NT-proBNP drop in 6 mo]
  I -- no response --> J[Switch / intensify<br>or daratumumab maintenance<br>or trial venetoclax t(11;14)+]
  I -- response --> K[Continue dara monthly maintenance<br>or stop after CR]

Pearls / Pitfalls

• Periorbital purpura + macroglossia = AL amyloid until proven otherwise — board's favorite gestalt.
• Cardiac involvement defines prognosis. Mayo stage III / IV (high NT-proBNP + troponin) = median OS months without treatment. Daratumumab-CyBorD (ANDROMEDA) is now standard frontline — superior hematologic + organ response vs CyBorD.
• Stage IV (Eur IIIb) is excluded from auto-HCT (perioperative mortality >25 %). These pts go to lower-intensity dara-based therapy; cardiac transplant + sequential auto-HCT in highly selected centers.
• Factor X deficiency (amyloid binds factor X) → unexplained bleeding; correct with FFP/PCC/recombinant factor X. Splenectomy historically tried (rare now).
• Subtype confirmation is mandatory — ATTR amyloid (especially ATTR-wild-type "senile") can co-exist with monoclonal gammopathy and would be mistreated as AL.
• t(11;14) AL amyloid → consider venetoclax at relapse (BCL2-driven).
• Treatment must be cautious — patients are fragile; bortezomib + lenalidomide can worsen heart failure / autonomic dysfunction. Dexamethasone causes fluid retention → low-dose preferred.
• Hematologic response (sFLC) precedes organ response (NT-proBNP, eGFR, alk phos) by months. Don't switch therapy too fast.
• Auto-HCT mortality ~5–7 % in selected pts (vs <1 % in MM) — careful selection.
• CyBorD (cyclophosphamide + bortezomib + dex) was prior standard — replaced by D-CyBorD frontline.

Cross-references

• MM — co-existence and overlap
• Light-chain MGUS — early AL screen
• Drug Regimens — D-CyBorD, venetoclax
• Cytogenetics Atlas — t(11;14)

相關題目

• Q-063 — Light-chain MGUS — AL amyloid screening
• Q-064 — AL amyloid — clinical recognition
• Q-065 — AL amyloid — frontline therapy (ANDROMEDA)
• Q-066 — AL amyloid — Mayo cardiac stage IV
• Q-147 — AL amyloid — auto-HCT eligibility

Sources