What is the role of plasma exchange in treating severe paraneoplastic disorders?

Role of Plasma Exchange in Treating Severe Paraneoplastic Disorders

Plasma exchange should be used as an adjunctive therapy for specific severe paraneoplastic disorders, particularly those with antibody-mediated pathophysiology, but is not recommended as monotherapy. Plasma exchange is most effective when combined with immunosuppressive therapies and when initiated early in the disease course.

Mechanism and Rationale

Plasma exchange (plasmapheresis) works by:

• Mechanically removing circulating antibodies from the bloodstream
• Separating plasma from cellular blood components through membrane filtration or centrifugation
• Reconstituting blood with albumin, fresh-frozen plasma, or crystalloid before reinfusion 1

In paraneoplastic syndromes, plasma exchange targets:

• Circulating pathogenic antibodies
• Complement activation products 1

Evidence-Based Indications for Plasma Exchange

Recommended Uses:

1. Antibody-Mediated Paraneoplastic Neurological Syndromes

   • Anti-Yo syndrome (paraneoplastic cerebellar degeneration)
   • Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC
   • Anti-NMDA receptor encephalitis 1, 2

2. Severe Vasculitis with Paraneoplastic Features

   • May be considered in ANCA-associated vasculitis with serum creatinine >300 μmol/L due to active glomerulonephritis 1
   • Diffuse alveolar hemorrhage with hypoxemia 1

Not Recommended:

• Routine use for alveolar hemorrhage in ANCA-associated vasculitis 1
• As monotherapy for any paraneoplastic syndrome 1
• For paraneoplastic syndromes with primarily T-cell-mediated pathology (e.g., most anti-Hu syndromes) 1

Treatment Protocol

Typical plasma exchange regimen for paraneoplastic disorders:

• Exchange 1-2 plasma volumes per session
• Sessions performed on alternate days
• 5-14 total procedures depending on clinical response
• Replacement with 5% albumin and/or fresh-frozen plasma 1, 2

Combination Therapy Approach

Plasma exchange should be combined with:

1. Immunosuppressive medications:

   • High-dose corticosteroids (methylprednisolone 1g/day for 3 days)
   • Cyclophosphamide for severe cases
   • Rituximab for B-cell mediated disorders 1, 3

2. Treatment of underlying malignancy:

   • Tumor removal/treatment is critical and carries the best chance of clinical stabilization or remission 3

Efficacy and Response Rates

• Response rates vary by syndrome type:

  • Group 2 paraneoplastic syndromes (antibodies against cell surface antigens): 75% response rate 4, 3
  • Group 1 paraneoplastic syndromes (antibodies against intracellular antigens): lower response rates 3

• Early initiation of plasma exchange appears more beneficial than delayed treatment 2

Potential Complications

• Hypotensive episodes (most common, ~11% of procedures)
• Cutaneous vasculitis (rare)
• Increased risk of serious infections when combined with immunosuppression 1, 2
• Complications related to vascular access

Key Clinical Considerations

1. Timing is critical:

   • Initiate plasma exchange early in the disease course
   • Clinical improvement is unlikely in patients with longstanding symptoms 3

2. Patient selection:

   • Most beneficial in antibody-mediated syndromes
   • Less effective in T-cell-mediated paraneoplastic disorders 1

3. Sequence of therapies:

   • Some evidence suggests better outcomes when plasma exchange precedes IVIg rather than follows it 2

4. Duration of therapy:

   • Continue until clinical improvement or stabilization
   • Consider additional courses for relapses

Conclusion

Plasma exchange represents an important adjunctive therapy for severe paraneoplastic disorders, particularly those with antibody-mediated pathophysiology. Its efficacy is enhanced when combined with appropriate immunosuppressive therapies and treatment of the underlying malignancy. Early intervention is associated with better outcomes, highlighting the importance of prompt diagnosis and treatment initiation.