Submitted July 18, 2006
Accepted August 31, 2006
Safety and efficacy of risk adapted cyclophosphamide,
thalidomide and dexamethasone in systemic AL amyloidosis
Ashutosh D Wechalekar*, Hugh J.B. Goodman, Helen J. Lachmann, Mark Offer, Philip N. Hawkins, and Julian D. Gillmore
National Amyloidosis Centre, Royal Free and UCL Medical School, London, UK
* Corresponding author; email: a.wechalekar{at}medsch.ucl.ac.uk.
High dose melphalan with stem cell transplantation is believed to the most effective treatment for systemic AL amyloidosis, but many patients are ineligible due to the extent of their disease and treatment related mortality (TRM) remains substantial. We report the use of a risk adapted oral regimen of cyclophosphamide, thalidomide and dexamethasone (CTD) or attenuated CTD (CTDa) in 75 patients with advanced AL amyloidosis including 44 patients with clonal relapse after prior therapy. Fifty one (68%) patients received CTD and 24 (32%) received CTDa. A hematological response occurred in 48 (74%) of 65 evaluable patients including complete responses in 14 (21%) and partial responses in 34 (53%) cases. Median estimated overall survival (OS) from commencement of treatment was 41 months and from diagnosis median not reached with a median follow up 22 months. Three year estimated OS was 100% and 82% among complete and partial hematological responders respectively. Toxicity necessitating cessation of therapy occurred in 8%, and was 
grade 2 in 52% of patients. TRM was 4%. The clonal response rates to CTD reported here are higher than any previously reported non transplant regimen in AL amyloidosis and risk adaptation allows its use in poorer risk patients. CTD merits prospective randomized study.
