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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 754-762
Prolonged CD4 depletion after sequential autologous peripheral
blood progenitor cell infusions in children and young adults
Crystal L. Mackall,
Dagmar Stein,
Thomas A. Fleisher,
Margaret R. Brown,
Frances T. Hakim,
Catherine V. Bare,
Susan F. Leitman,
Elizabeth J. Read,
Charles S. Carter,
Leonard H. Wexler, and
Ronald E. Gress
From the Pediatric Oncology Branch, Medicine Branch, Experimental
Immunology Branch, National Cancer Institute and Department of
Transfusion Medicine, Clinical Center, National Institutes of Health,
Bethesda, MD.
Administration of mobilized peripheral blood progenitor cells
(PBPCs) after high-dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of such products to restore lymphocyte populations remains unclear. In this report, we evaluated immune reconstitution in a series of patients treated with sequential cycles
of high-dose chemotherapy, followed by autologous PBPC infusions
(median CD34+ cell dose
7.2 × 106 cells/kg [range 2-29.3]).
Although patients experienced rapid reconstitution of B cells and
CD8+ T cells, we observed CD4 depletion and diminished
immune responsiveness in all patients for several months after
completion of therapy. Mature CD4+ T cells contained
within the grafts did not appear to contribute substantially to immune
reconstitution because CD4 counts did not differ between recipients of
unmanipulated T-cell replete infusions versus CD34 selected,
T-cell-depleted infusions. Rather, at 12 months after therapy, total
CD4 count was inversely proportional to age ( =  0.78,
P = .04), but showed no relationship to CD34 cell dose
( = 0.42, P = .26), suggesting that age-related
changes within the host are largely responsible for the limited immune reconstitution observed. These results demonstrate that in the autologous setting, the infusion of large numbers of PBPCs is not
sufficient to restore T-cell immune competence and emphasize that
specific approaches to enhance immune reconstitution are necessary if
immune-based therapy is to be used to eradicate minimal residual
disease after autologous PBPC transplantation.
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