Establishing a platform for immunotherapy: Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients

Claude Sportes, Nicole J. McCarthy, Frances Hakim, Seth M. Steinberg, David J. Liewehr, David Weng, Shivaani Kummar, Juan Gea-Banacloche, Catherine K. Chow, Robert M. Dean, Kathleen M. Castro, Donna Marchigiani, Michael R. Bishop, Daniel H. Fowler, Ronald E. Gress

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)472-483
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2005

Keywords

  • Autologous stem cell transplantation
  • Breast cancer
  • High-dose chemotherapy
  • Immune reconstitution

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Sportes, C., McCarthy, N. J., Hakim, F., Steinberg, S. M., Liewehr, D. J., Weng, D., Kummar, S., Gea-Banacloche, J., Chow, C. K., Dean, R. M., Castro, K. M., Marchigiani, D., Bishop, M. R., Fowler, D. H., & Gress, R. E. (2005). Establishing a platform for immunotherapy: Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients. Biology of Blood and Marrow Transplantation, 11(6), 472-483. https://doi.org/10.1016/j.bbmt.2005.03.010