title: Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide-based chemotherapy.
abstract: BACKGROUND
  The incidence of herpes zoster is substantial during bortezomib treatment in patients with multiple myeloma (MM).
  
  
  OBJECTIVE
  This study aimed to elucidate the effect of chemotherapy with or without bortezomib in MM patients on their herpes zoster incidence and varicella zoster virus (VZV)-specific cell-mediated immunity (CMI).
  
  
  METHODS
  Peripheral blood mononuclear cells were collected at baseline and after 1 month of bortezomib-based or thalidomide-based chemotherapy and then analyzed using VZV-specific interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. The clinical data from these patients were analyzed in relation to the ELISPOT results.
  
  
  RESULTS
  Of 58 patients analyzed, 39 patients received bortezomib and the other 19 patients, thalidomide. Among them, 5 patients developed herpes zoster during chemotherapy; all 5 were being treated with the bortezomib-based regimen and were not receiving prophylactic anti-viral agents. The median onset of herpes zoster was 32 days (range, 15-95 days) from the initiation of chemotherapy. Among patients who received bortezomib therapy, acyclovir prophylaxis significantly reduced the risk for herpes zoster (100-day cumulative incidence, 0% vs. 49.5%; p<0.001). Spot-forming cell (SFC) counts in the IFN-γ ELISPOT assay decreased from baseline after bortezomib (p=0.011) or thalidomide (p=0.096) treatment. Patients with baseline SFCs greater than 20/10(6) mononuclear cells exhibited significantly higher incidence of herpes zoster (100-day cumulative incidence, 34.8% vs. 0%; p=0.040).
  
  
  CONCLUSIONS
  Bortezomib treatment significantly reduced VZV-specific CMI, and high baseline SFC counts in patients receiving this treatment without acyclovir prophylaxis were associated with a significantly increased risk for herpes zoster.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yeung-Chul
authors.initials: YC
authors.lastname: Mun
authors.affiliation: Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, VHS Medical Center, Seoul, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Pyoeng Gyun
authors.initials: PG
authors.lastname: Choe
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: wbpark1@snu.ac.kr.
authors.forename: Wan Beom
authors.initials: WB
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: kim_dajung@hanmail.net.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D005260:Female; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C573415:IFNG protein, human; D013792:Thalidomide; D000069286:Bortezomib; D007371:Interferon-gamma
keywords: Bortezomib; Enzyme-linked immunospot assay; Herpes zoster; Multiple myeloma; Varicella-zoster virus