Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial.

Abstract

High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving < or =2 organ systems were assigned to MEL 100, 140, or 200 mg/m(2) with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients.

• Authors: Adam D Cohen, Ping Zhou, Joanne Chou, Julie Teruya-Feldstein, Lilian Reich, Hani Hassoun, Beth Levine, Daniel A Filippa, Elyn Riedel, Tarun Kewalramani, Michael D Stubblefield, Martin Fleisher, Stephen Nimer, Raymond L Comenzo
• Journal: British journal of haematology (Br J Haematol) Vol. 139 Issue 2 Pg. 224-33 (Oct 2007) ISSN: 0007-1048 [Print] England
• PMID: 17897298 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Adjuvants, Pharmaceutic
• Immunoglobulin Light Chains
• Myeloablative Agonists
• Thalidomide
• Dexamethasone
• Melphalan

Topics

• Adjuvants, Immunologic (therapeutic use)
• Adjuvants, Pharmaceutic (therapeutic use)
• Adult
• Aged
• Amyloidosis (immunology, mortality, therapy)
• Combined Modality Therapy
• Dexamethasone (therapeutic use)
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunoglobulin Light Chains
• Male
• Melphalan (therapeutic use)
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Proportional Hazards Models
• Remission Induction
• Risk Assessment
• Survival Rate
• Thalidomide (therapeutic use)
• Transplantation, Autologous