title: A case of refractory multiple myeloma with proliferation of large granular lymphocytes by lenalidomide treatment and its association with clinical efficacy.
abstract: A 72-year-old Japanese male was diagnosed as having monoclonal gammopathy of undetermined significance and was followed up without therapy. Three years later, the patient progressed to symptomatic multiple myeloma. Melphalan + prednisolone was administered as first-line chemotherapy for ~6 years. Since the patient was judged to exhibit refractory multiple myeloma, he subsequently received radiation therapy on the lumbar spine. The patient was enrolled in a clinical trial and received lenalidomide + lowdose dexamethasone (Rd) therapy. The patient achieved very good partial remission following four cycles of Rd. At this time, large granular lymphocytes (LGLs) increased to 25-40% of peripheral blood leukocytes, however, the LGLs were present in the blood (~8%) prior to lenalidomide treatment. By flow cytometry of surface antigens, it was revealed that the LGLs were positive for cluster of differnetiation (CD)2, 7, 8, 16, 56, and 57, and human leukocyte antigen-D related, however, were negative for CD3, 4 and 5, suggesting that these LGLs predominantly exhibited an natural killer (NK) cell phenotype. T-cell receptor β gene rearrangement was not detected by polymerase chain reaction. A51Cr release assay was performed to investigate whether the NK cells actually possessed activity. A low level of M protein was sustained for ~15 months. This implied the enhancement of immune activation during lenalidomide treatment. The present case study suggested that LGL cells induced by lenalidomide may contribute to long-term restraint of myeloma cells. This immune system component may contribute to disease control.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan; Department of Hematology, St. Mary's Hospital, Kurume, Fukuoka 830-8543, Japan.
authors.forename: Michitoshi
authors.initials: M
authors.lastname: Hashiguchi
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Kuniki
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Koteda
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morishige
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Eijirou
authors.initials: E
authors.lastname: Oku
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takata
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Seki
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Mouri
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Osaki
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Yoshimoto
authors.affiliation: Department of Hematology, St. Mary's Hospital, Kurume, Fukuoka 830-8543, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
keywords: immunomodulatory drugs; immunomodulatory function; large granular lymphocytes; lenalidomide; multiple myeloma