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Anti-B-cell monoclonal antibody-purged autologous bone marrow
transplantation for B-cell non-Hodgkin's lymphoma: phenotypic
reconstitution and B-cell function
A Pedrazzini, AS Freedman, J Andersen, L Heflin, K Anderson, T Takvorian, GP Canellos, J Whitman, F Coral and J Ritz
Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
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.
Volume 74,
Issue 6,
pp. 2203-2211,
11/01/1989
Copyright © 1989 by The American Society of Hematology
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