A 62-year-old woman from Delhi presents with progressive bilateral carpal tunnel syndrome, shoulder pain, and recurrent pathological fractures of the humerus. Serum calcium and phosphate are normal. Bone marrow examination shows 15% plasma cells. Serum protein electrophoresis reveals an M-spike of 2.8 g/dL (monoclonal λ light chain). Tissue biopsy from a shoulder lesion confirms amyloid deposition. What is the most appropriate next step in management?

Question

Accepted Answer

D. Initiate bortezomib-based chemotherapy after cardiac and renal assessment. ## Management of AL-Amyloidosis with Systemic Involvement

**Key Point:** AL-amyloidosis with evidence of plasma cell dyscrasia (elevated M-spike, monoclonal light chain, >10% bone marrow plasma cells) requires immediate chemotherapy after baseline organ assessment to prevent progressive multi-organ failure.

### Diagnostic Features Pointing to AL-Amyloidosis
- Monoclonal λ light chain on serum protein electrophoresis (M-spike 2.8 g/dL)
- Elevated bone marrow plasma cells (15%) → clonal disorder
- Tissue-confirmed amyloid deposition
- Carpal tunnel syndrome (amyloid arthropathy) + pathological fractures (bone infiltration)
- Systemic manifestations (multi-organ involvement)

### AL-Amyloidosis: Diagnostic Criteria & Treatment Algorithm

```mermaid
flowchart TD
  A[Tissue-confirmed amyloidosis]:::outcome --> B{Immunofluorescence/MS: AL or ATTR?}:::decision
  B -->|AL-amyloidosis| C[Assess cardiac, renal, hepatic function]:::action
  B -->|ATTR-amyloidosis| D[Genetic testing; start tafamidis]:::action
  C --> E{Cardiac involvement present?}:::decision
  E -->|Yes| F[Echocardiography, troponin, BNP]:::action
  E -->|No| G[Proceed to chemotherapy]:::action
  F --> H{NYHA III-IV or elevated biomarkers?}:::decision
  H -->|Yes| I[Cautious chemotherapy + supportive care]:::action
  H -->|No| J[Standard bortezomib-based chemotherapy]:::action
  I --> K[Monitor for toxicity]:::action
  J --> K
  K --> L[Assess response at 3 months]:::decision
  L -->|Good response| M[Continue chemotherapy]:::action
  L -->|Poor response| N[Consider stem cell transplant if eligible]:::action
```

**High-Yield:** AL-amyloidosis management priorities:
1. **Baseline assessment:** Cardiac (echo, troponin, BNP), renal (creatinine, proteinuria), hepatic (LFTs)
2. **Chemotherapy:** Bortezomib-based regimens (bortezomib + dexamethasone ± cyclophosphamide) are first-line
3. **Stem cell transplantation:** Reserved for younger, fit patients with good organ function who respond to induction chemotherapy
4. **Supportive care:** Diuretics, ACE inhibitors, bisphosphonates for bone disease

**Clinical Pearl:** The presence of monoclonal light chain with systemic amyloid deposition defines AL-amyloidosis as a hematologic malignancy requiring chemotherapy. Unlike ATTR-amyloidosis (managed with tafamidis), AL-amyloidosis is progressive without treatment and demands immediate chemotherapy to halt plasma cell proliferation and amyloid production.

**Mnemonic: AL-AMYLOIDOSIS WORKUP = CARDIAC**
- **C**ardiac assessment (echo, troponin, BNP)
- **A**ssess renal function (creatinine, proteinuria)
- **R**enal biopsy if proteinuria >3 g/day
- **D**etermine organ involvement (liver, GI, nervous system)
- **I**nitiate chemotherapy (bortezomib-based)
- **A**void stem cell transplant in advanced cardiac disease
- **C**ontinue supportive care (diuretics, ACE-I, bisphosphonates)

**Warning:** ~~Tafamidis is for ATTR-amyloidosis~~ (hereditary or wild-type transthyretin), NOT AL-amyloidosis. Tafamidis stabilizes transthyretin tetramers; it has no role in light-chain amyloidosis.

[cite:Harrison 21e Ch 329; Robbins 10e Ch 6]

Answer

A. Observe with serial imaging; start treatment only if M-spike increases

Answer

B. Start tafamidis and supportive care with bisphosphonates

Answer

C. Perform stem cell transplantation immediately

Explanation

Management of AL-Amyloidosis with Systemic Involvement

Diagnostic Features Pointing to AL-Amyloidosis

AL-Amyloidosis: Diagnostic Criteria & Treatment Algorithm

Practice similar questions

Join our NEET PG community