title: Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.
abstract: Bortezomib and melphalan have synergistic effects against multiple myeloma (MM) cells. We conducted a pilot study on the combination of bortezomib and high-dose melphalan (Bor-HDM) as a conditioning regimen followed by autologous stem cell transplant (ASCT) in 17 Japanese patients with newly diagnosed MM, in comparison with a historical control of patients who received high-dose melphalan (HDM) only followed by ASCT. Nine patients received a single dose of bortezomib 1.3 mg/m(2) on day -1 in combination with melphalan 100 mg/m(2) on days -3 and -2 (Bor1-HDM), and eight received two doses of bortezomib 1.3 mg/m(2) on days -4 and -1 (Bor2-HDM) in combination with HDM. Engraftment of autologous peripheral blood stem cells and regimen-related toxicities (RRT) were comparable among the HDM and Bor-HDM groups. Probability of upgrading from a less than very good partial response (VGPR) to VGPR after ASCT was approximately two times higher in the Bor-HDM group than in the HDM group. However, we observed no significant differences in engraftment, RRT, and response rates between the Bor1-HDM and Bor2-HDM groups. The present study showed that concurrent administration of at least two doses of bortezomib in combination with HDM can be safe in Japanese patients. Additional large prospective randomized trials are required to address the optimal dosages and schedules of bortezomib administration, as well as the efficacy of the Bor-HDM conditioning regimen for ASCT.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan, toshmiya@intmed1.med.kyushu-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Goichi
authors.initials: G
authors.lastname: Yoshimoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kamimura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Muta
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Takashima
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ito
authors.forename: Motoaki
authors.initials: M
authors.lastname: Shiratsuchi
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Katsuto
authors.initials: K
authors.lastname: Takenaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan