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Megakaryocytic progenitors can be generated ex vivo and safely administered
to autologous peripheral blood progenitor cell transplant recipients
F Bertolini, M Battaglia, P Pedrazzoli, GA Da Prada, A Lanza, D Soligo, L Caneva, B Sarina, S Murphy, T Thomas and GR della Cuna
Division of Medical Oncology, IRCCS Maugeri Foundation, Pavia Medical
Center, Italy.
We evaluated different culture conditions to obtain a lineage-selected
proliferation of clonogenic megakaryocytic progenitors (MP). In low-
density (LD) or CD34+ cell cultures, the best results were obtained in
serum-free medium in the presence of megakaryocyte growth and development
factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL- 11, FLT-ligand,
and macrophage inflammatory protein-1alpha. In paired studies, expansion of
LD cells was less effective than expansion of CD34+ cells, and
pre-enrichment of CD34+ cells using negative depletion of lineage-positive
cells produced significantly larger quantities of MP than pre-enrichment
using positive selection. MP proliferation peaked on day 7 in culture, and
an 8- +/- 5-fold expansion of CD34+/CD61+ cells, a 17- +/- 5-fold expansion
of colony-forming units- megakaryocytes, and a 58- +/- 14-fold expansion of
the total number of CD61+ cells was obtained. In a feasibility clinical
study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's
lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC)
transplant received MP generated ex vivo (range, 1 to 21 x 10(5)/kg CD61
cells) together with unmanipulated PBPC. Eight patients received a single
allogeneic platelet transfusion, whereas platelet transfusion support was
not needed in 2 of the 4 patients receiving the highest doses of cultured
MP. This result compares favorably with a retrospective control group of 14
patients, all requiring platelet transfusion support. Adverse reactions or
bacterial contamination of cell cultures have not been observed. In
conclusion, MP can be expanded ex vivo and safely administered to
autologous transplant recipients. Further clinical trials will indicate the
reinfusion schedule able to consistently abrogate the need for allogeneic
platelet transfusion support in autologous transplantation.
Volume 89,
Issue 8,
pp. 2679-2688,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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