TY - JOUR
T1 - Establishing a platform for immunotherapy
T2 - Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients
AU - Sportés, Claude
AU - McCarthy, Nicole J.
AU - Hakim, Frances
AU - Steinberg, Seth M.
AU - Liewehr, David J.
AU - Weng, David
AU - Kummar, Shivaani
AU - Gea-Banacloche, Juan
AU - Chow, Catherine K.
AU - Dean, Robert M.
AU - Castro, Kathleen M.
AU - Marchigiani, Donna
AU - Bishop, Michael R.
AU - Fowler, Daniel H.
AU - Gress, Ronald E.
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
KW - Autologous stem cell transplantation
KW - Breast cancer
KW - High-dose chemotherapy
KW - Immune reconstitution
UR - http://www.scopus.com/inward/record.url?scp=19944384599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944384599&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2005.03.010
DO - 10.1016/j.bbmt.2005.03.010
M3 - Article
C2 - 15931636
AN - SCOPUS:19944384599
SN - 1083-8791
VL - 11
SP - 472
EP - 483
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -