Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2169-2174
Autologous transplantation of ex vivo expanded bone marrow cells
grown from small aliquots after high-dose chemotherapy for breast
cancer
Patrick Stiff,
Bohao Chen,
Wilbur Franklin,
David Oldenberg,
Eric Hsi,
Robert Bayer,
Elizabeth Shpall,
Judy Douville,
Ramkumar Mandalam,
Deepak Malhotra,
Thomas Muller,
R. Douglas Armstrong, and
Alan Smith
From the Departments of Medicine and Pathology, Loyola University
Medical Center, Maywood, IL; Aastrom Biosciences, Ann Arbor, MI;
and the Department of Pathology and Medicine, University of Colorado
Medical Center, Denver, CO.
The collection of small aliquots of bone marrow (BM), followed by ex
vivo expansion for autologous transplantation may be less morbid, and
more cost-effective, than typical BM or blood stem cell harvesting.
Passive elimination of contaminating tumor cells during expansion could
reduce reinoculation risks. Nineteen breast cancer patients underwent
autotransplants exclusively using ex vivo expanded small aliquot BM
cells (900-1200 × 106). BM was expanded in media
containing recombinant flt3 ligand, erythropoietin, and PIXY321, using
stromal-based perfusion bioreactors for 12 days, and infused after
high-dose chemotherapy. Correlations between cell dose and engraftment
times were determined, and immunocytochemical tumor cell assays were
performed before and after expansion. The median volume of BM expanded
was 36.7 mL (range 15.8-87.0). Engraftment of neutrophils greater than
500/µL and platelets greater than 20 000/µL were 16 (13-24) and 24 (19-45) days, respectively; 1 patient had delayed
platelet engraftment, even after infusion of back-up BM. Hematopoiesis
is maintained at 24 months, despite posttransplant radiotherapy in 18 of the 19 patients. Transplanted CD34+/Lin
(lineage negative) cell dose correlated with neutrophil and platelet engraftment, with patients receiving greater than
2.0 × 105 CD34+/Lin cells
per kilogram, engrafting by day 28. Tumor cells were observed in 1 of
the 19 patients before expansion, and in none of the 19 patients after
expansion. It is feasible to perform autotransplants solely with BM
cells grown ex vivo in perfusion bioreactors from a small aliquot.
Engraftment times are similar to those of a typical 1000 to 1500 mL BM
autotransplant. If verified, this procedure could reduce the risk of
tumor cell reinoculation with autotransplants and may be valuable in
settings in which small stem cell doses are available, eg, cord blood transplants.
