Can prednisone (corticosteroid) use after Bone Marrow Transplant (BMT) increase the risk of cancer recurrence?

Prednisone After Bone Marrow Transplantation and Cancer Recurrence Risk

Prednisone use after bone marrow transplantation (BMT) does not directly cause cancer recurrence, but requires careful management as prolonged use may increase risk of secondary malignancies through immunosuppression. The evidence does not support a direct causal relationship between prednisone and primary cancer recurrence post-BMT.

Prednisone's Role in Post-BMT Care

Immunosuppression and Cancer Risk

• Immunosuppressive medications, including corticosteroids like prednisone, are necessary after BMT to prevent graft-versus-host disease (GVHD), but must be balanced against potential risks 1
• Long-term use of immunosuppressive agents is associated with an increased risk of de novo malignancies (new cancers, not recurrence of the original disease) 1
• The risk of malignancy from immunosuppressants appears more related to dosage rather than the specific type of agent used 1

Steroid Tapering Guidelines

• For patients with chronic GVHD, steroids should be tapered gradually once there is a response to treatment 2
• Initial dosing typically ranges from 0.5-1 mg/kg/day of prednisone or equivalent, with tapering beginning when:
  • Complete resolution of GVHD is observed
  • Improvement in at least one organ without progression in others
• Common tapering approach:
  • Maintain initial dose for 4-8 weeks if responding
  • Reduce by 25% of initial dose at weeks 8-12 if continued response
  • Subsequent reductions of 10-25% every 2-4 weeks as tolerated 2

Cancer Recurrence vs. Secondary Malignancies

Primary Cancer Recurrence

• The evidence does not support that prednisone directly causes recurrence of the original cancer for which BMT was performed
• In multiple myeloma patients who underwent BMT, maintenance therapy decisions are based on risk stratification rather than concerns about prednisone specifically causing recurrence 1
• For patients with autoimmune hepatitis who underwent liver transplantation, corticosteroid withdrawal should be performed cautiously due to risk of disease recurrence, suggesting steroids may actually help prevent recurrence in some conditions 1

Secondary Malignancy Risk

• De novo malignancies are a leading cause of mortality following the first post-transplant year 1
• The incidence of de novo cancers ranges from 3% to 26%, with continuous rise in risk up to 19% at 10 years and 34% at 15 years post-transplant 1
• Risk factors for secondary malignancies include:
  • Loss of immunovigilance from immunosuppressive agents
  • Viral infections with oncogenic potential (e.g., EBV, HPV)
  • Pre-existing conditions (e.g., PSC)
  • Lifestyle factors (smoking, alcohol) 1

Special Considerations for Different Transplant Types

Allogeneic BMT

• If the bone marrow and subsequent organ transplant (e.g., kidney) are from the same donor, patients may require little or no maintenance immunosuppression 3
• In some cases where prednisone was administered from day 0 through 35 along with methotrexate/cyclosporine, there were unexpected increases in acute and chronic GVHD in HLA-identical recipients 4
• The timing of prednisone administration matters - starting prednisone on day 15 (after completion of methotrexate) showed better outcomes than starting on day 0 4

Autologous BMT

• For multiple myeloma patients post-autologous BMT, lenalidomide maintenance therapy has shown improved survival and is now standard of care, with no specific concerns about prednisone causing recurrence 1
• For patients intolerant of lenalidomide, bortezomib maintenance every 2 weeks may be considered 1

Monitoring and Management Recommendations

1. Regular cancer surveillance is essential for all post-BMT patients, especially those on long-term immunosuppression
2. Minimize steroid exposure when possible:
   • Use the lowest effective dose
   • Implement steroid-sparing strategies when appropriate
   • Follow established tapering protocols
3. Risk-stratified approach to immunosuppression management:
   • For high-risk features (thrombocytopenia, extensive skin involvement), use more cautious tapering (10% reduction every 3-4 weeks)
   • For standard-risk patients, follow standard tapering protocols
4. Monitor for signs of both GVHD and cancer recurrence during steroid tapering

Conclusion

While prednisone and other immunosuppressants are associated with increased risk of de novo malignancies after BMT, there is no strong evidence that prednisone directly causes recurrence of the original cancer. The benefits of appropriate immunosuppression to prevent GVHD generally outweigh the risks of secondary malignancies in the short term, but long-term management should focus on minimizing immunosuppression while maintaining disease control.