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Relationship Between Disease Activity And Circulating Endothelial And Endothelial Progenitor Cells In Multiple Myeloma.

JOURNAL OF CLINICAL ONCOLOGY(2018)

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摘要
e20004 Background: A variety of tumor markers have been identified to define risk and predict and monitor treatment response in multiple myeloma (MM). Circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) may offer a non-invasive method to evaluate neoangiogenesis and its impact on bone marrow microvascular density which has been directly linked to inferior outcomes. Methods: 43 patients received a novel induction regimen of busulfan, melphalan, and bortezomib conditioning followed by autologous hematopoietic stem cell transplantation (AHSCT) in a single-center, open-label phase I/II trial. Peripheral blood samples were collected from 18 consecutively enrolled patients on trial at Day -6 and Day 0. Cell populations were detected by six-color flow cytometry with the final phenotype for CECs CD45-, CD31+, Syto16+, CD146+, CD133- and for CEPs CD45-, CD31+, Syto16+, CD146+, and CD133+. Results: Median age at transplant was 61 in this mostly high risk (13/18 ISS stage III) group. There was no meaningful change in CEC or CEP from Day -6 to Day 0 (table 1a). We found no difference in the risk of progression between those above and below the median CEP value at Day -6 (p = .21) or Day 0 (p = .59) (table 1b) and the change in CEP value from Day -6 to Day 0 was not associated with relapse (p = .53). Conclusions: CECs and CEPs in the peripheral blood did not correlate with disease activity and response. Alternate non-invasive means of disease monitoring in addition to standard para-protein studies need further exploration. Clinical trial information: NCT03.Table 1: Change in CEC and CEP a. Overall Change in CEC and CEP Valid N Day -6 Day 0 Exact p Median CEC (IQR) 18 0.331 (0.143-0.413) 0.586 (0.133-1.14) .054 Median CEP (IQR) 18 0.00162 (0.000178-0.00488) 0.00393 (0.000224-0.0316) .013 Note: IQR = Interquartile rangeNote: Units for CEP and CEC are in % of total nucleated cells isolated after Ficoll-Hypaque density-gradient centrifugation b. Risk of progression as function of CEP Value Valid N No Relapse Relapse Hazard Ratio (95% CI) p Day -6 18 2.42 (95% CI: 0.60 – 9.77) .21 CEP < 0.00162 6 (67%) 3 (33%) CEP < 0.00162 3 (33%) 6 (67%) Day 0 18 1.44 (0.38 – 5.40) .59 CEP < 0.00393 5 (56%) 4 (44%) CEP > = 0.00393 4 (44%) 5 (56%)
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关键词
endothelial progenitor cells,multiple myeloma,progenitor cells
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