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Retrovirally marked CD34-enriched peripheral blood and bone marrow cells
contribute to long-term engraftment after autologous transplantation
CE Dunbar, M Cottler-Fox, JA O'Shaughnessy, S Doren, C Carter, R Berenson, S Brown, RC Moen, J Greenblatt and FM Stewart
Hematology Branch, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD 20892-1652, USA.
We report here on a preliminary human autologous transplantation study of
retroviral gene transfer to bone marrow (BM) and peripheral blood
(PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or
breast cancer had cyclophosphamide and filgrastim-mobilized PB cells
CD34-enriched and transduced with a retroviral marking vector containing
the neomycin resistance gene, and CD34-enriched BM cells transduced with a
second marking vector also containing a neomycin resistance gene. After
high-dose conditioning therapy, both transduced cell populations were
reinfused and patients were followed over time for the presence of the
marker gene and any adverse effects related to the gene-transfer procedure.
All 10 evaluable patients had the marker gene detected at the time of
engraftment, and 3 of 9 patients had persistence of the marker gene for
greater than 18 months posttransplantation. The marker gene was detected in
multiple lineages, including granulocytes, T cells, and B cells. The source
of the marking was both the transduced PB graft and the BM graft, with a
suggestion of better long-term marking originating from the PB graft. The
steady- state levels of marking were low, with only 1:1000 to 1:10,000
cells positive. There was no toxicity noted, and patients did not develop
detectable replication-competent helper virus at any time
posttransplantation. These results suggest that mobilized PB cells may be
preferable to BM for gene therapy applications and that progeny of
mobilized peripheral blood cells can contribute long-term to engraftment of
multiple lineages.
Volume 85,
Issue 11,
pp. 3048-3057,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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