A case of refractory multiple myeloma with proliferation of large granular lymphocytes by lenalidomide treatment and its association with clinical efficacy

Hashiguchi,Michitoshi; Okamura,Takashi; Nomura,Kei; Nakamura,Takayuki; Kawaguchi,Kuniki; Koteda,Satoko; Morishige,Satoshi; Oku,Eijirou; Takata,Yuka; Seki,Ritsuko; Mouri,Fumihiko; Osaki,Koichi; Yoshimoto,Kohji; Imamura,Yutaka; Nagafuji,Koji

doi:10.3892/mco.2016.747

A case of refractory multiple myeloma with proliferation of large granular lymphocytes by lenalidomide treatment and its association with clinical efficacy

Authors:
- Michitoshi Hashiguchi
- Takashi Okamura
- Kei Nomura
- Takayuki Nakamura
- Kuniki Kawaguchi
- Satoko Koteda
- Satoshi Morishige
- Eijirou Oku
- Yuka Takata
- Ritsuko Seki
- Fumihiko Mouri
- Koichi Osaki
- Kohji Yoshimoto
- Yutaka Imamura
- Koji Nagafuji
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Affiliations: 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
Published online on: January 27, 2016 https://doi.org/10.3892/mco.2016.747
Pages: 574-578

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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. A 51Cr 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.

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