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Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma

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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/m2 on day −1 in combination with melphalan 100 mg/m2 on days −3 and −2 (Bor1-HDM), and eight received two doses of bortezomib 1.3 mg/m2 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.

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Acknowledgments

We thank the nursing staff who cared for the patients at the Fukuoka BMT group. This work was supported, in part, by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (23390254 & 24659462 to T.M.).

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Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Toshihiro Miyamoto, Goichi Yoshimoto, Tsuyoshi Muta, Shuichiro Takashima, Koji Kato & Koichi Akashi

  2. Department of Hematology, National Kyushu Medical Center, Fukuoka, Japan

    Goichi Yoshimoto

  3. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Tomohiko Kamimura & Yoshikiyo Ito

  4. Department of Medicine and Bioregulatory Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    Motoaki Shiratsuchi

  5. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

  6. Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

    Katsuto Takenaka, Hiromi Iwasaki, Takanori Teshima & Koichi Akashi

  7. Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University, Fukuoka, Japan

    Yasushi Takamatsu

  8. Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Takanori Teshima

Authors
  1. Toshihiro Miyamoto
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  2. Goichi Yoshimoto
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  3. Tomohiko Kamimura
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  4. Tsuyoshi Muta
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  5. Shuichiro Takashima
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  6. Yoshikiyo Ito
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  7. Motoaki Shiratsuchi
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  8. Ilseung Choi
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  9. Koji Kato
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  10. Katsuto Takenaka
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  11. Hiromi Iwasaki
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  12. Yasushi Takamatsu
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  13. Takanori Teshima
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  14. Koichi Akashi
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Correspondence to Toshihiro Miyamoto.

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Miyamoto, T., Yoshimoto, G., Kamimura, T. et al. Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma. Int J Hematol 98, 337–345 (2013). https://doi.org/10.1007/s12185-013-1402-0

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  • DOI: https://doi.org/10.1007/s12185-013-1402-0

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