High-Dose Melphalan and Autologous Stem-Cell Transplantation in Patients with AL Amyloidosis: An 8-Year Study

  1. Martha Skinner, MD;
  2. Vaishali Sanchorawala, MD;
  3. David C. Seldin, MD, PhD;
  4. Laura M. Dember, MD;
  5. Rodney H. Falk, MD;
  6. John L. Berk, MD;
  7. Jennifer J. Anderson, PhD;
  8. Carl O'Hara, MD;
  9. Kathleen T. Finn, RN, NP;
  10. Caryn A. Libbey, MD;
  11. Janice Wiesman, MD;
  12. Karen Quillen, MD;
  13. Niall Swan, MD; and
  14. Daniel G. Wright, MD
  1. From Boston University School of Medicine, Boston, Massachusetts.

    Abstract

    Background: AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective.

    Objective: To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation.

    Design: 8-year longitudinal analysis of clinical effectiveness.

    Setting: University-affiliated specialty referral clinic.

    Patients: 701 consecutive new patients with AL amyloidosis.

    Intervention: High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status.

    Measurements: Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation.

    Results: Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates.

    Conclusions: Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.

    Article and Author Information

    • Acknowledgments: The authors appreciate the contributions of former members of the Amyloid Treatment and Research Program and the Stem Cell Transplant Program who participated in the initial years of this work. They gratefully acknowledge the excellent data management of Arquimedes Areche and Akira Murakami and the patient coordination of Salli Fennessey, Karen Donovan, Serena Baqui, Ceit McCaleb, Lisa Marie Paul, and Julie Cosio. They also thank the many nurses, particularly Rick Kunz, stem-cell transplant nurse coordinator, who participated in the care of these patients.

    • Grant Support: By grants from the National Institutes of Health (HL 68705), U.S. Food and Drug Administration (FD-R-001346), the Gerry Foundation, the Young Family Amyloid Research Fund, the Sue Sellors Finley Cardiac Amyloid Research Fund, and the Amyloid Research Fund at Boston University. Dr. Seldin is a Scholar of the Leukemia and Lymphoma Society of America.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Martha Skinner, MD, Amyloid Treatment and Research Program, K503, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118; e-mail, mskinner{at}bu.edu.

    • Current Author Addresses: Drs. Skinner, Sanchorawala, Seldin, Dember, Falk, Berk, Anderson, O'Hara, Finn, Libbey, Wiesman, Quillen, Swan, and Wright: Amyloid Treatment and Research Program, K503, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118.

    • Author Contributions: Conception and design: M. Skinner, D.C. Seldin, L.M. Dember, J.L. Berk, C. O'Hara, D.G. Wright,

    • Analysis and interpretation of the data: M. Skinner, V. Sanchorawala, D.C. Seldin, L.M. Dember, R.H. Falk, J.J. Anderson, D.G. Wright.

    • Drafting of the article: M. Skinner, V. Sanchorawala, D.C. Seldin, R.H. Falk, D.G. Wright.

    • Critical revision of the article for important intellectual content: M. Skinner, V. Sanchorawala, D.C. Seldin, L.M. Dember, J.L. Berk, C. O'Hara, J. Wiesman, K. Quillen, D.G. Wright.

    • Final approval of the article: M. Skinner, V. Sanchorawala, D.C. Seldin, L.M. Dember, R.H. Falk, J.L. Berk, J.J. Anderson, C. O'Hara, K.T. Finn, C.A. Libbey, J. Wiesman, K. Quillen, N. Swan, D.G. Wright.

    • Provision of study materials or patients: M. Skinner, V. Sanchorawala, D.C. Seldin, R.H. Falk, J.L. Berk, K. Quillen, N. Swan, D.G. Wright.

    • Statistical expertise: J.J. Anderson.

    • Obtaining of funding: M. Skinner.

    • Administrative, technical, or logistic support: M. Skinner, K.T. Finn, K. Quillen, N. Swan, D.G. Wright.

    • Collection and assembly of data: M. Skinner, C.A. Libbey, J. Wiesman, K. Quillen, N. Swan, D.G. Wright.

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    1. Ann Intern Med January 20, 2004 vol. 140 no. 2 85-93
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