Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer.
The present study examines the nature of humoral and cellular immune reconstitution in 28 patients with advanced breast cancer following high-dose chemotherapy with stem cell rescue. Patients underwent testing of T, B, NK and dendritic cell function at serial time points until 1 year post transplant or until the time of disease progression. Abnormalities in T cell phenotype and function were observed following high-dose chemotherapy that persisted for at least 6-12 months. The vast majority of patients experienced an inversion of the CD4/CD8 ratio and demonstrated an anergic response to candida antigen. Mean T cell proliferation in response to PHA and to co-culture with allogeneic monocytes was significantly compromised. In contrast, mean IgG and IgA levels were normal 6 months post transplant and NK cell yields and function were transiently elevated following high-dose chemotherapy. Dendritic cells generated from peripheral blood progenitors displayed a characteristic phenotype and were potent inducers of allogeneic T cell proliferation in the post-transplant period. The study demonstrates that patients undergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction. In contrast, B, NK, and DC recover more rapidly. These findings carry significant implications for the design of post-transplant immunotherapy.
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
D
D
Avigan
Z
Z
Wu
R
R
Joyce
A
A
Elias
P
P
Richardson
D
D
McDermott
J
J
Levine
L
L
Kennedy
N
N
Giallombardo
D
D
Hurley
J
J
Gong
D
D
Kufe
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000276:immunology*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016516:CD4-CD8 Ratio / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007109:Immunity / Q000187:drug effects; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D007239:Infections / Q000139:chemically induced; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D012008:Recurrence; D012882:Skin Tests; D014181:Transplantation Immunology / Q000276:immunology*
D007136:Immunoglobulins; D010835:Phytohemagglutinins