title: High-dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study.
abstract: Amyloid light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which monoclonal light chains transform to amyloid deposit in various tissues and can lead to organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10-14 months. With high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT), haematological and clinical remission rates of up to 50% of treated patients have been reported from phase II studies. HDM followed by ASCT appears to prolong survival in patients, if haematological remission can be reached. In this phase II study, we evaluated vincristine, adriamycin and dexamethasone (VAD) as induction chemotherapy prior to stem cell mobilization and HDM with ASCT. The regimen was, in general, feasible in patients with AL amyloidosis, but VAD chemotherapy had a considerable World Health Organization (WHO) grade III-IV toxicity (25%) and mortality (7%) rate. VAD pretreatment did not interfere with stem cell mobilization and HDM with ASCT was possible in 86% of patients. The overall treatment efficacy was comparable with reported results of HDM and ASCT without preceding chemotherapy. We could not show an additional benefit of VAD induction in terms of increasing haematological response rate; however the 13% mortality rate after HDM and ASCT in our series was lower than the previous report.
authors.affiliation: Department of Haematology/Oncology, Clinic of Internal Medicine, University of Heidelberg, 69120 Heidelberg, Germany. Jolanta_Perz@med.uni-heidelberg.de
authors.forename: Jolanta B
authors.initials: JB
authors.lastname: Perz
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Schonland
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Reinhold P
authors.initials: RP
authors.lastname: Linke
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000401:mortality / Q000628:therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D012074:Remission Induction; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D008558:Melphalan