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

14 Citations (Scopus)

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

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Stem Cell Transplantation
Immunotherapy
Stem Cells
Outcome Assessment (Health Care)
Breast Neoplasms
Drug Therapy
Cancer Vaccines
T-Lymphocytes
Disease-Free Survival
Reference Values
Melphalan
Residual Neoplasm
Etoposide
Paclitaxel
Cyclophosphamide
Clinical Studies
Neoplasms
Cell Count
Transplantation
Mortality

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Establishing a platform for immunotherapy : Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients. / Sportes, Claude; McCarthy, Nicole J.; Hakim, Frances; Steinberg, Seth M.; Liewehr, David J.; Weng, David; Kummar, Shivaani; Gea-Banacloche, Juan; Chow, Catherine K.; Dean, Robert M.; Castro, Kathleen M.; Marchigiani, Donna; Bishop, Michael R.; Fowler, Daniel H.; Gress, Ronald E.

In: Biology of Blood and Marrow Transplantation, Vol. 11, No. 6, 01.06.2005, p. 472-483.

Research output: Contribution to journalArticle

Sportes, C, McCarthy, NJ, Hakim, F, Steinberg, SM, Liewehr, DJ, Weng, D, Kummar, S, Gea-Banacloche, J, Chow, CK, Dean, RM, Castro, KM, Marchigiani, D, Bishop, MR, Fowler, DH & Gress, RE 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, vol. 11, no. 6, pp. 472-483. https://doi.org/10.1016/j.bbmt.2005.03.010
Sportes, Claude ; McCarthy, Nicole J. ; Hakim, Frances ; Steinberg, Seth M. ; Liewehr, David J. ; Weng, David ; Kummar, Shivaani ; Gea-Banacloche, Juan ; Chow, Catherine K. ; Dean, Robert M. ; Castro, Kathleen M. ; Marchigiani, Donna ; Bishop, Michael R. ; Fowler, Daniel H. ; Gress, Ronald E. / Establishing a platform for immunotherapy : Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients. In: Biology of Blood and Marrow Transplantation. 2005 ; Vol. 11, No. 6. pp. 472-483.
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