Analysis of circulating tumor cells in patients with multiple myeloma during the course of high-dose therapy with peripheral blood stem ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-05

AUTHORS

K Kiel, FW Cremer, C Rottenburger, C Kallmeyer, E Ehrbrecht, A Atzberger, U Hegenbart, H Goldschmidt, M Moos

ABSTRACT

In multiple myeloma (MM) circulating CD19+ cells have been considered as myeloma precursors. As these cells are also possibly a reservoir of treatment resistant disease evaluation of the CD19+ cells during the course of high-dose therapy has to be a major concern. We determined the number of tumor cells in the CD19+ as well as CD19- fractions of PB of eight patients with disease sensitive to VA[I]D chemotherapy, of 10 patients who achieved partial or complete remission post-high-dose therapy (HDT) with peripheral blood stem cell transplantation (PBSCT) and of a further seven patients with disease progression post-transplantation. CD19+ cell fractions were obtained by preparative sequential magnetic and fluorescence activated cell sorting with a median purity of 97.1%. In addition, PB samples of seven patients post-transplantation were sorted for CD20+ cells (median purity, 98.7%). The number of tumor cells in the CD19+, the CD19- and the CD20+ fractions were determined using a quantitative CDR3 PCR assay. The number of CD19+ tumor cells in patients in remission post-HDT was similar to those of the patients post-VA[I]D (median, 1.05 vs 0.92 CD19+ tumor cells/ml PB, P = 0.72) providing evidence for the persistence of this tumor cell fraction during the course of HDT. This was in contrast to the CD19- compartment, in which the number of tumor cells was significantly reduced in those patients in remission post-transplantation (median, 53 vs 0 CD19- tumor cells/ml PB; P = 0.006). In patients with progressive disease the number of tumor cells in both cell fractions was significantly higher (CD19+: median, 1.05 vs 21 tumor cells/ml PB, P = 0.05; CD19-: 0 vs 63 tumor cells/ml PB, P = 0.008). While the absolute number of CD19+ cells was reduced in the group of patients after VA[I]D treatment, a polyclonal CD19+ reconstitution had occurred in patients responding to HDT. The tumor cell content in the CD19+ fractions could be confirmed by the results obtained analyzing the CD20+ cell fractions. In conclusion, these results indicate that disease progression after PBSCT in MM is accompanied by an expansion of tumor cells in both the CD19+ and CD19- fractions. Similar numbers of CD19+ clonotypic cells post-HDT suggest that these cells persist and thus, contribute to disease dissemination and relapse. More... »

PAGES

1019

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bmt.1701767

DOI

http://dx.doi.org/10.1038/sj.bmt.1701767

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10373068


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45 schema:description In multiple myeloma (MM) circulating CD19+ cells have been considered as myeloma precursors. As these cells are also possibly a reservoir of treatment resistant disease evaluation of the CD19+ cells during the course of high-dose therapy has to be a major concern. We determined the number of tumor cells in the CD19+ as well as CD19- fractions of PB of eight patients with disease sensitive to VA[I]D chemotherapy, of 10 patients who achieved partial or complete remission post-high-dose therapy (HDT) with peripheral blood stem cell transplantation (PBSCT) and of a further seven patients with disease progression post-transplantation. CD19+ cell fractions were obtained by preparative sequential magnetic and fluorescence activated cell sorting with a median purity of 97.1%. In addition, PB samples of seven patients post-transplantation were sorted for CD20+ cells (median purity, 98.7%). The number of tumor cells in the CD19+, the CD19- and the CD20+ fractions were determined using a quantitative CDR3 PCR assay. The number of CD19+ tumor cells in patients in remission post-HDT was similar to those of the patients post-VA[I]D (median, 1.05 vs 0.92 CD19+ tumor cells/ml PB, P = 0.72) providing evidence for the persistence of this tumor cell fraction during the course of HDT. This was in contrast to the CD19- compartment, in which the number of tumor cells was significantly reduced in those patients in remission post-transplantation (median, 53 vs 0 CD19- tumor cells/ml PB; P = 0.006). In patients with progressive disease the number of tumor cells in both cell fractions was significantly higher (CD19+: median, 1.05 vs 21 tumor cells/ml PB, P = 0.05; CD19-: 0 vs 63 tumor cells/ml PB, P = 0.008). While the absolute number of CD19+ cells was reduced in the group of patients after VA[I]D treatment, a polyclonal CD19+ reconstitution had occurred in patients responding to HDT. The tumor cell content in the CD19+ fractions could be confirmed by the results obtained analyzing the CD20+ cell fractions. In conclusion, these results indicate that disease progression after PBSCT in MM is accompanied by an expansion of tumor cells in both the CD19+ and CD19- fractions. Similar numbers of CD19+ clonotypic cells post-HDT suggest that these cells persist and thus, contribute to disease dissemination and relapse.
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