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Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells
Y Gazitt, CC Reading, R Hoffman, A Wickrema, DH Vesole, S Jagannath, J Condino, B Lee, B Barlogie and G Tricot
Department of Medicine, University of Arkansas for Medical Sciences, Little
Rock, CA 72205, USA.
High-dose therapy with autologous marrow or peripheral blood stem cell
(PBSC) rescue has been extensively applied in the treatment of multiple
myeloma (MM) patients during the past 10 years resulting in improved
event-free and overall survival when compared with standard chemotherapy.
However, relapses are common and cure is unlikely in the majority of
patients. Because both bone marrow and PBSCs are contaminated with myeloma
cells it is conceivable that relapse after autotransplantation originates
at least in part from autografted tumor cells. In this study, mobilized
PBSCs were examined for the presence of myeloma cells based on
immunophenotyping and sensitive polymerase chain reaction (PCR)-based
techniques. In addition, CD34+ Lin- Thy+ stem cells were purified from
mobilized PBSC harvests of 10 MM patients by sequentially using counterflow
elutriation centrifugation, treatment with phenylalanine methylester, and
flow sorting, using 5-parameter gating (propidium iodide, forward scatter,
side scatter, CD34+ v Lin- and CD34+ v Thy+). Virtually all mobilized
unsorted PBSC preparations contained myeloma cells in sufficient quantities
(range, < 0.01 to > 10%) potentially causing a disease relapse. Stem
cell purification led to an overall enrichment by about 50-fold in all 10
patients; approximately 90% of the final cell population expressed CD34+
Lin- Thy+ with no evidence of myeloma cell contamination based on flow
cytometric analysis of CD38bright cells (< 0.1%). Quantitative PCR
amplification of patient-specific complementarity determining region III
(CDRIII) DNA sequences showed depletion of clonal B cells by 2.7 to 7.3
logs, with the highest log reduction noted in the samples initially
containing the most tumor cells. Our results show that purification of
CD34+ Lin- Thy+ cells depletes myeloma cells to undetectable levels from up
to 10% present in unsorted PBSCs, thus offering a tool to investigate
whether MM relapse after autotransplantation can be reduced markedly.
Volume 86,
Issue 1,
pp. 381-389,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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