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).

Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment

“…Transplant‐related mortality rates have decreased from as high as 40% to 4% to 7% in current studies . Extended follow up of 69 patients enrolled in a SCT trial reported a median survival of 96 and 120 months for the transplanted cohort . Excluding patients from SCT whose NT‐proBNP levels are >5,000 pg mL −1 can reduce therapy‐related mortality rates to 1% .…”

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light‐chain amyloidosis

“…In one trial, the median survival of all patients was 96 months from registration; for patients undergoing SCT, the median survival was 10 years from the date of transplantation. The 30‐day mortality rate after SCT was 4% . To address the confusion regarding the optimal therapy for amyloidosis, this trial was initiated to compare high‐dose melphalan with stem cell reconstitution to oral melphalan plus dexamethasone.…”

“…The 30-day mortality rate after SCT was 4%. 17 To address the confusion regarding the optimal therapy for amyloidosis, this trial was initiated to compare high-dose melphalan with stem cell reconstitution to oral melphalan plus dexamethasone.…”

Extensive purpuric lesions on the face

“…Daneben kommen auch andere Substanzen zur Anwendung, wie zum Beispiel Thalidomid oder Lenalidomid [1]. Bei fortgeschrittener Erkrankung kann auch eine autologe Stammzelltransplantation in Erwägung gezogen werden [8]. Insgesamt ist die Prognose der Erkrankung ungünstig.…”