title: Extended follow up of high-dose melphalan and autologous stem cell transplantation after vincristine, doxorubicin, dexamethasone induction in amyloid light chain amyloidosis of the prospective phase II HOVON-41 study by the Dutch-Belgian Co-operative Trial Group for Hematology Oncology.
abstract: In a prospective multicenter phase II study, we evaluated the effect of three courses of vincristine, doxorubicin and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation on an intention-to-treat basis. Sixty-nine newly diagnosed patients with amyloid light chain amyloidosis were included between November 2000 and January 2006: 37 men and 32 women with a median age of 56 years, including 46% of patients with cardiac and 22% of patients with involvement of 3 or 4 organs. Initial results presented in 2008 showed a 4-year overall survival rate of 62% among all the patients, while the 4-year survival rate after transplantation was 78%. Here we report the long-term follow-up data after a median follow up of 115 months of the patients still alive. Median survival of all patients was 96 months from registration and for the transplanted patients ten years from the date of transplantation. Twelve (12%) patients died during induction therapy with vincristine, doxorubicin and dexamethasone, including 8 patients (12%) due to treatment-related mortality. Two patients died within one month following high-dose melphalan. We conclude that vincristine, doxorubicin and dexamethasone should not be applied as induction therapy for intensification in amyloid light chain amyloidosis. However, a 2-step approach consisting of a non-intensive less toxic induction therapy followed by high-dose melphalan and autologous stem cell transplantation may result in extended survival in newly diagnosed patients with amyloid light chain amyloidosis (clinicaltrials.gov identifier: 01207094).
authors: University Medical Center Groningen, The Netherlands.
authors: Bouke P C
authors: BP
authors: Hazenberg
authors: Radboud University Medical Center Nijmegen, The Netherlands.
authors: Alexandra
authors: A
authors: Croockewit
authors: Erasmus MC Cancer Institute, Clinical Trial Center, The Netherlands.
authors: Bronno
authors: B
authors: van der Holt
authors: VU University Medical Center, Amsterdam, The Netherlands.
authors: Sonja
authors: S
authors: Zweegman
authors: Academic Hospital Maastricht, The Netherlands.
authors: Gerard M J
authors: GM
authors: Bos
authors: University Hospital Gasthuisberg, Leuven, Belgium.
authors: Michel
authors: M
authors: Delforge
authors: University Medical Center Utrecht, The Netherlands.
authors: Reinier A P
authors: RA
authors: Raymakers
authors: Erasmus MC, Rotterdam, The Netherlands.
authors: Pieter
authors: P
authors: Sonneveld
authors: University Medical Center Groningen, The Netherlands.
authors: Edo
authors: E
authors: Vellenga
authors: Haga Hospitals, Den Haag, The Netherlands.
authors: Pierre W
authors: PW
authors: Wijermans
authors: Leiden University Medical Center, The Netherlands.
authors: Peter A
authors: PA
authors: von dem Borne
authors: Amsterdam Medical Center, The Netherlands.
authors: Marinus H
authors: MH
authors: van Oers
authors: Antonius Hospital, Nieuwegein, The Netherlands.
authors: Okke
authors: O
authors: de Weerdt
authors: Erasmus MC Cancer Institute, Clinical Trial Center, The Netherlands.
authors: Fokje M
authors: FM
authors: Spoelstra
authors: VU University Medical Center, Amsterdam, The Netherlands h.lokhorst@vumc.nl.
authors: Henk M
authors: HM
authors: Lokhorst
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D012074:Remission Induction; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D008558:Melphalan