title: Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma.
abstract: We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.
authors: Department of Hematology, University Hospital Utrecht, The Netherlands.
authors: H M
authors: HM
authors: Lokhorst
authors: P
authors: P
authors: Sonneveld
authors: J J
authors: JJ
authors: Cornelissen
authors: P
authors: P
authors: Joosten
authors: M
authors: M
authors: van Marwijk Kooy
authors: J
authors: J
authors: Meinema
authors: H K
authors: HK
authors: Nieuwenhuis
authors: M H
authors: MH
authors: van Oers
authors: D J
authors: DJ
authors: Richel
authors: C N
authors: CN
authors: Segeren
authors: G
authors: G
authors: Veth
authors: L F
authors: LF
authors: Verdonck
authors: P W
authors: PW
authors: Wijermans
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D008558:Melphalan