title: Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients.
abstract: Tumor vaccine after high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) aims at directing immune recovery toward tumor responses after optimizing minimal residual disease. We have characterized T-cell recovery and tumor response after a regimen devised as a platform for such immunotherapy. One hundred patients with high-risk or metastatic breast cancer received 3 to 7 cycles of paclitaxel and cyclophosphamide (overall response rate, 78%) and then HDC with melphalan and etoposide. Seventy-one patients received HDC and ASCT (no mortality at 100 days). At 24 months after transplantation, progression-free and overall survival probabilities for patients with stage IIIA, IIIB, and IV disease were 82%, 81%, and 42% and 100%, 94%, and 68%, respectively. The median progression-free and overall survivals from entry on study for stage IV patients were 15.3 and 38.1 months, respectively. CD3 + , CD8 + , and CD4 + cells were severely depleted after ASCT. Although total CD8 + T-cell numbers approached the normal range by 3 months, most of these cells were CD28 - . Naive CD45RA + CD4 + T cells approached the normal range only 18 months after ASCT and only in younger patients. The described observations provide the basis for devising a strategy for cancer vaccine administration after ASCT. Incorporating immune reconstitution enhancement after ASCT may be advantageous.
authors.affiliation: Experimental Transplantation & Immunology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr., CRC Room 43142, Bethesda, MD 20892-1203, USA. kastensc@mail.nih.gov
authors.forename: Claude
authors.initials: C
authors.lastname: Sportès
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: McCarthy
authors.forename: Frances
authors.initials: F
authors.lastname: Hakim
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: David
authors.initials: D
authors.lastname: Weng
authors.forename: Shivaani
authors.initials: S
authors.lastname: Kummar
authors.forename: Juan
authors.initials: J
authors.lastname: Gea-Banacloche
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chow
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dean
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Castro
authors.forename: Donna
authors.initials: D
authors.lastname: Marchigiani
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D014182:Transplantation, Autologous; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines