Autologous peripheral blood stem cell transplantation for double-refractory myeloma with <i>K-RAS</i> and <i>N-RAS</i> mutations

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  • JIMBO Koji
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • YOKOYAMA Kazuaki
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • OGAWA Miho
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • HIRANO Mitsuhito
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • OCHI Kiyosumi
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • KOBAYASHI Masayuki
    Division of Molecular Therapy, Advanced Research Center, the Institute of Medical Science, the University of Tokyo
  • YUSA Nozomi
    Department of Applied Genomics, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • SHIMIZU Eigo
    Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Science, the University of Tokyo
  • KAWAMATA Toyotaka
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • YASUI Hiroshi
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • OHNO Nobuhiro
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • YAMAGUCHI Rui
    Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Science, the University of Tokyo
  • IMOTO Seiya
    Division of Health Medical Data Science, Health Intelligence Center, the Institute of Medical Science, the University of Tokyo
  • FURUKAWA Yoichi
    Department of Applied Genomics, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • MIYANO Satoru
    Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Science, the University of Tokyo
  • IMAI Yoichi
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo
  • TOJO Arinobu
    Department of Hematology/Oncology, Research Hospital, the Institute of Medical Science, the University of Tokyo Division of Molecular Therapy, Advanced Research Center, the Institute of Medical Science, the University of Tokyo

Bibliographic Information

Other Title
  • 自家末梢血幹細胞移植が奏効した<i>K-RAS</i>/<i>N-RAS</i>変異陽性double-refractory myeloma
  • 症例報告 第6回日本血液学会関東甲信越地方会 奨励賞 自家末梢血幹細胞移植が奏効したK-RAS/N-RAS変異陽性double-refractory myeloma
  • ショウレイ ホウコク ダイ6カイ ニホン ケツエキ ガッカイ カントウ コウシンエツチホウカイ ショウレイショウ ジカ マッショウケツ カンサイボウ イショク ガ ソウコウ シタ K-RAS/N-RAS ヘンイ ヨウセイ double-refractory myeloma

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Abstract

<p>The prognosis of multiple myeloma (MM) has been improved due to the introduction of novel agents like proteasome inhibitors and immunomodulatory drugs (IMiDs). However, some cases are refractory to the use of novel agents, and the prognosis of such cases is poor. A 53-year-old male was diagnosed with MM and categorized as follows: Bence-Jones protein lambda type MM, Durie-Salmon IIIA, international staging system (ISS) stage II, and revised ISS stage II. Mutations in K-RAS and IGH/FGFR3 translocation were detected at diagnosis. His tumor was refractory to seven therapeutic regimens including bortezomib, IMiDs (lenalidomide, thalidomide, pomalidomide), conventional chemotherapy, and radiation therapy. N-RAS mutations, CKS1B gains, and C-MYC split signals were detected after treatment. We performed high-dose melphalan/autologous stem cell transplantation (HD-MEL/ASCT) as a salvage therapy and achieved very good partial response. The correlation between K-RAS mutations and poor prognosis or between N-RAS mutations and reduced sensitivity to bortezomib is reported. However, RAS mutations are reported as a favorable factor for HD-MEL/ASCT. In general, mutations of both the K-RAS and N-RAS are known to be mutually exclusive. This rare MM case has mutations in both K-RAS and N-RAS, and the possible relevance of these mutations to both the refractoriness to novel therapies and sensitivity to HD-MEL/ASCT is suggested.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 58 (12), 2380-2385, 2017

    The Japanese Society of Hematology

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