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Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation high-dose chemotherapies for patients with advanced diffuse large B-cell lymphoma

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Abstract

Even after the advent of rituximab, clinical outcomes of conventional immuno-chemotherapy for high-risk diffuse large B-cell lymphoma (DLBCL) remain unsatisfactory. We retrospectively evaluated the efficacy and safety of R-Double-CHOP (R-D-CHOP), consisting of rituximab (375 mg/m2, day −2), cyclophosphamide (750 mg/m2, day 1, 2), doxorubicin (50 mg/m2, day 1, 2), vincristine [1.4 mg/m2 (maximum 2.0 mg/body), day 1], and prednisolone (50 mg/m2, day 1–5), followed by consolidation high-dose chemotherapy. This treatment was given to 51 de novo DLBCL patients with a median age of 54 (range 19–65), who were categorized as high/high-intermediate risk by the age-adjusted International Prognostic Index. Treatment was given every 3 weeks up to three courses. The overall response and the complete response rate for R-D-CHOP were 94 and 78 %, respectively. A total of 30 responders proceeded to high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT), whereas 16 received high-dose methotrexate (HD-MTX) alternatively. The 3-year overall survival and the event-free survival for all patients were 78 and 61 %, respectively. Major adverse events included hematological toxicities, but there were no treatment-related deaths during the observation period. We conclude that the R-D-CHOP regimen followed by HDC/ASCT or HD-MTX is a promising treatment option for younger patients with highly advanced DLBCL.

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Acknowledgments

The authors are most grateful to Dr. Umihiko Sawada and Dr. Tetsuo Yamazaki for their enormous contribution to the development of this work.

Conflict of interest

K. Miura received lecture fee from Chugai Pharmaceutical Co. Ltd, Kyowa Hakko Kirin Co., Ltd; Sumitomo Dainippon Pharma Co., Ltd. Y. Hatta received lecture fee from Chugai Pharmaceutical Co. Ltd; and Kyowa Hakko Kirin Co., Ltd. M. Takei received research funding from Teijin Pharma Limited, Chugai Pharmaceutical Co. Ltd, CSL Behring K. K, Kyowa Hakko Kirin Co., Ltd, Japan Blood Products Organization, Torii, Phamaceutical Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd., Alexion Pharmaceuticals, Yakult Honsha Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. The other authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Department of Hematology and Rheumatology, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi-ku, Tokyo, Japan

      Daisuke Kurita, Katsuhiro Miura, Masaru Nakagawa, Shimon Ohtake, Masashi Sakagami, Yoshihito Uchino, Hiromichi Takahashi, Satomi Kiso, Atsuko Hojo, Hitomi Kodaira, Mai Yagi, Yukio Hirabayashi, Yujin Kobayashi, Noriyoshi Iriyama, Sumiko Kobayashi, Yoshihiro Hatta & Masami Takei

    2. Division of Hematology and Oncology, Kasukabe Municipal Hospital, Kasukabe-shi, Saitama, Japan

      Atsuko Hojo & Yoshimasa Kura

    3. Department of Pathology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan

      Masahiko Sugitani

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    1. Daisuke Kurita
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    Correspondence to Katsuhiro Miura or Yoshihiro Hatta.

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    D. Kurita and K. Miura have equally contributed.

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    Kurita, D., Miura, K., Nakagawa, M. et al. Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation high-dose chemotherapies for patients with advanced diffuse large B-cell lymphoma. Int J Hematol 101, 585–593 (2015). https://doi.org/10.1007/s12185-015-1780-6

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