title: Mobilization of peripheral blood stem cells (PBSCs) after etoposide, adriamycin and cisplatin therapy, and a multimodal cell therapy approach with PBSCs in advanced gastric cancer.
abstract: The EAP combination of etoposide (ETP), doxorubicin (ADM) and cisplatin (CDDP) has been reported to be highly active for advanced gastric cancer. However, it is associated with severe myelotoxicity, and its use has declined. We examined whether peripheral blood stem cells (PBSCs) could be mobilized during hematopoietic recovery after EAP, and assessed the possibility of using multimodal cell therapy with PBSCs for the treatment of advanced gastric cancer. Five men with advanced gastric adenocarcinoma were enrolled. All patients were chemotherapy-naïve. EAP (ETP, 360 mg/m2; ADM, 40 mg/m2; CDDP, 80 mg/m2) was given to each patient, and myelotoxicity was carefully monitored. Granulocyte colony-stimulating factor was administered after the neutrophil nadir, and PBSCs were collected by leukapheresis during hematopoietic recovery. The median nadir of the neutrophil count after EAP was 225/ml, occurring between day 17 and 20. Sufficient numbers of PBSCs [CD34(+) cells, CFU-GM] could be mobilized in 4/5 patients. A 45-year-old patient with extended lymph node metastasis received high-dose EAP with peripheral blood stem cell transplantation (PBSCT), followed by cancer vaccine therapy with dendritic cells (DCs), induced from cryopreserved PBSCs. Both high-dose EAP with PBSCT and DC-based immunotherapy was safely performed for the first time against gastric cancer. Although associated with severe myelotoxicity, EAP can mobilize sufficient numbers of PBSCs during hematopoietic recovery. Multimodal cell therapy combining high-dose chemotherapy with PBSCT and DC-based immunotherapy is feasible and can be a reasonable approach in advanced gastric cancer.
authors.affiliation: Department of Surgery and Oncology of Digestive System, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. yueda@koto.kpu-m.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiki
authors.forename: Sachio
authors.initials: S
authors.lastname: Harada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kimura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Imura
authors.forename: Kei
authors.initials: K
authors.lastname: Naito
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nomura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology; D004317:Doxorubicin / Q000008:administration & dosage*; D005047:Etoposide / Q000008:administration & dosage*; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013274:Stomach Neoplasms / Q000628:therapy*; D013997:Time Factors
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin