Unfractionated peripheral blood stem cell autografts and CD(34+)-enriched autografts have similar long-term culture initiating capacity in multiple myeloma

CD(34+)-enriched peripheral blood stem cells (PBSC) are increasingly being used as an autograft in patients with multiple myeloma (MM). The rationale for the use of the CD34+-enriched fraction in MM is the ability to obtain a graft with a significant reduction of contamination by plasma cells. Howev...

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Published in:Hematology and cell therapy 1999-11, Vol.41 (5), p.197-204
Main Authors: Turhan, A G, Bourhis, J H, Bonnet, M L, Novault, S, Bayle, C, Bennaceur, A, Vainchenker, W, Pico, J L, Beaujean, F
Format: Article
Language:English
Subjects:
Adult
Antigens, CD34 - blood
Antigens, CD34 - metabolism
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Behavior Therapy - methods
Cell Culture Techniques
Cell Division
Clone Cells
Cytapheresis - methods
Dexamethasone - administration & dosage
Doxorubicin - administration & dosage
Female
Hematopoietic Stem Cell Mobilization - methods
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic Stem Cells - cytology
Humans
Male
Middle Aged
Multiple Myeloma - therapy
Transplantation, Autologous - methods
Vincristine - administration & dosage
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Summary:CD(34+)-enriched peripheral blood stem cells (PBSC) are increasingly being used as an autograft in patients with multiple myeloma (MM). The rationale for the use of the CD34+-enriched fraction in MM is the ability to obtain a graft with a significant reduction of contamination by plasma cells. However, the effect of such a manipulation on the proliferating potential of the engrafted cells is not known. We wished to study, as part of a randomized trial comparing the outcome in MM patients transplanted with either CD(34+)-enriched cells or unfractionated PBSC, the primitive hematopoietic cell content of the autografts using long-term culture initiating cell (LTC-IC) assays in 7 MM patients. In 3 patients CD(34+)cell-enriched fraction was compared to unfractionated PBSC whereas in the remaining 4 patients the LTC-IC assay was performed on total PBSC. The mean percentage of CD34+ cells of the CD34+ selected fraction in three patients was 82% (range 71%-96%) whereas the same percentage in PBSC varied from 0.6% to 10% in 4 patients (mean: 4.2%). Out of three patients transplanted with CD34+ cell fraction, two patients were found to have a very similar LTC-IC generating potential in their CD34+ versus PBSC fractions as this was assessed by the clonogenic cell output at week+5 per 10(4) CD34+ cells initiating the culture (PBSC: 92 and 168 and CD34+ fraction: 102 and 16, respectively) whereas one patient had a slightly different values (PBSC: 51 and CD34+ fraction: 103). When the PBSC fraction was compared in all 7 patients, the LTC-IC generation potential was very heterogenous, varying from 1.4 to 168. To determine if the selection procedure influences the numbers of LTC-IC's in both fractions, we have performed limiting dilution assays to determine both the frequency of distribution of hematopoietic colonies and the frequency of LTC-IC's in two patients. The frequency of distribution of hematopoietic colonies was linear in both CD34+ and PBSC fractions as was the frequency of LTC-IC when the corrections were made with regard to the CD34+ cell-content of the cultures (1/20). Our results indicate that the CD34+ selection procedure used in all three patients (Ceprate) is not deleterious for the generation of LTC-IC's and these findings support the rationale for the use of this procedure in multiple for the purposes of tumor depletion.
ISSN:1269-3286
1279-8509