Anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation for B-cell non-Hodgkin's lymphoma: phenotypic reconstitution and B-cell function.
In the present report we have attempted to examine immunologic reconstitution following high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-purged autologous bone marrow transplantation (ABMT). By cell-surface phenotypic analysis, the majority of patients had normal percentage of natural killer cells (NK), monocytes, and CD8+ T cells at one month post-ABMT. In contrast, the percentage of CD4+ T cells was reduced for at least 3 years, and the CD4:CD8 ratio reflected this imbalance. B-cell reconstitution was slightly prolonged, with normal percentage and absolute numbers of CD20+ B cells evident by 3 months. Although B cells returned by 3 months, in vitro assessment of B-cell function demonstrated impairment of proliferative responses to either anti-immunoglobulins bound to beads (anti-Ig), Epstein-Barr virus (EBV), or interleukin-2 (IL-2) for approximately 1 year and low molecular B-cell growth factor (BCGF) for approximately 2 or more years. Moreover, in vivo B-cell reconstitution demonstrated a more selective defect, with normal levels of immunoglobulin IgM returning at 6 months, IgG at 12 months, and IgA after 2 years. Despite normal numbers of B cells and relative normal levels of Ig early following ABMT, our in vitro data suggest an intrinsic defect in B-cell responsiveness. Moreover, these defects are similar to those observed following nonpurged autologous and allogeneic BMT, although the interval of immune impairment appears more prolonged.
Pedrazzini
A
A
Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Freedman
A S
AS
Andersen
J
J
Heflin
L
L
Anderson
K
K
Takvorian
T
T
Canellos
G P
GP
Whitman
J
J
Coral
F
F
Ritz
J
J
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D007136:Immunoglobulins / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000601:surgery*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013997:Time Factors; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4