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Positively selected autologous blood CD34+ cells and unseparated peripheral
blood progenitor cells mediate identical hematopoietic engraftment after
high-dose VP16, ifosfamide, carboplatin, and epirubicin
W Brugger, R Henschler, S Heimfeld, RJ Berenson, R Mertelsmann and L Kanz
Department of Hematology/Oncology, Albert Ludwigs University Freiburg
Medical Center, Germany.
To investigate the feasibility of peripheral blood CD34+ cell selection and
to analyze CD34+ cell-mediated engraftment after high-dose chemotherapy, we
performed a phase I/II trial in 21 patients with advanced malignancies. The
rationale for the selection of CD34+ cells from peripheral blood progenitor
cell (PBPC) collections is based on the observation that contaminating
tumor cells can be depleted approximately 3 logs using this procedure.
CD34+ cells from chemotherapy+granulocyte colony-stimulating
factor-mobilized PBPCs were positively selected with an avidin-biotin
immunoadsorption column (CEPRATE SC system). One leukapheresis product with
a median number of 2.8 x 10(6) CD34+ cells/kg was labeled with a
biotinylated anti-CD34 monoclonal antibody and subsequently processed over
the column. The yield of selected CD34+ cells was 73% +/- 24.6%. The purity
of the CD34+ cell fraction was 61.4% +/- 19.7%. CD34+ cells were shown to
represent predominantly committed progenitors coexpressing CD33, CD38, and
HLA-DR molecules (lin+). They gave rise to myeloid as well as erythroid and
multilineage colonies in vitro. In addition, positively selected CD34+
cells also comprised early hematopoietic progenitor cells, as shown by the
presence of CD34+/lin- cells. Transfusion of positively selected CD34+
cells (2.5 x 10(6) CD34+/kg; range, 0.45 to 5.1) after high-dose VP16
(1,500 mg/m2), ifosfamide (12 g/m2), carboplatin (750 mg/m2), and
epirubicin (150 mg/m2) (VIC-E) in 15 patients resulted in a rapid and
stable engraftment of hematopoiesis without any adverse events. As compared
with 13 historical control patients reconstituted with a comparable number
of unseparated PBPCs, time to neutrophil and platelet recovery was
identical in both groups (absolute neutrophil count > 500/microL, day +
12; platelet count > 50,000/microL, day + 15). These data indicate that
autologous peripheral blood CD34+ cells and unseparated PBPCs mediate
identical reconstitution of hematopoiesis after high-dose VIC-E
chemotherapy. Because positive selection of CD34+ cells from mobilized
blood results in a median 403-fold depletion of T cells, allogeneic CD34+
cells from mobilized blood should be investigated as an alternative to bone
marrow cells for allotransplantation.
Volume 84,
Issue 5,
pp. 1421-1426,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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