Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis: Results of a phase II trial Journal Article


Authors: Cohen, A. D.; Zhou, P.; Chou, J.; Teruya-Feldstein, J.; Reich, L.; Hassoun, H.; Levine, B.; Filippa, D. A.; Riedel, E.; Kewalramani, T.; Stubblefield, M. D.; Fleisher, M.; Nimer, S.; Comenzo, R. L.
Article Title: 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 ≤2 organ systems were assigned to MEL 100, 140, or 200 mg/m2 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. © 2007 The Authors.
Keywords: adult; clinical article; human tissue; treatment response; aged; middle aged; survival rate; thalidomide; clinical trial; constipation; fatigue; mortality; drug withdrawal; side effect; treatment duration; combined modality therapy; follow up; follow-up studies; phase 2 clinical trial; proportional hazards models; peripheral neuropathy; drug administration schedule; dexamethasone; melphalan; amyloidosis; autologous stem cell transplantation; deep vein thrombosis; stem cell transplantation; hematopoietic stem cell transplantation; risk assessment; risk; hyperglycemia; pneumonia; lung embolism; confidence interval; history; drug fatality; plasma cell; feasibility study; kidney function; acetylsalicylic acid; proton pump inhibitor; nucleotide sequence; cell damage; transient ischemic attack; remission induction; liver disease; anxiety; cell clone; drug dose titration; adjuvants, immunologic; immunoglobulin light chains; cotrimoxazole; granulocyte colony stimulating factor; gastrointestinal disease; transplantation, autologous; heart amyloidosis; bone necrosis; fluconazole; clinical trials; anticoagulant agent; cellulitis; docusate sodium; myeloablative agonists; sinusitis; pyridoxine; mania; systemic light chain amyloidosis; risk-adapted melphalan; amyloid neuropathy; kidney amyloidosis; adjuvants, pharmaceutic
Journal Title: British Journal of Haematology
Volume: 139
Issue: 2
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2007-10-01
Start Page: 224
End Page: 233
Language: English
DOI: 10.1111/j.1365-2141.2007.06783.x
PUBMED: 17897298
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 32" - "Export Date: 17 November 2011" - "CODEN: BJHEA" - "Molecular Sequence Numbers: GENBANK: X72813, X93620, X93627, X93638, Z22202, Z73647, Z73664, Z73673;" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Joanne Fu-Lou Chou
    157 Chou
  2. Julie T Feldstein
    288 Feldstein
  3. Adam D Cohen
    42 Cohen
  4. Raymond L Comenzo
    112 Comenzo
  5. Ping Zhou
    43 Zhou
  6. Hani Hassoun
    149 Hassoun
  7. Stephen D Nimer
    345 Nimer
  8. Martin Fleisher
    242 Fleisher
  9. Lilian M Reich
    77 Reich
  10. Daniel A Filippa
    102 Filippa
  11. Beth Mara Levine
    2 Levine