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Myeloid-Derived Suppressor Cells Absolute Counts in Predicting Durable Response to R-Chop in Patients with Follicular Lymphoma

Journal of clinical oncology(2011)

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摘要
e18504 Background: High amounts of CD68+ macrophages in tumor micro-environment (TAM) have been shown to correlate with prognosis in pts. with follicular lymphoma (FL). In order to identify an additional marker with prognostic significance we evaluated the circulating levels of myeloid derived suppressor cells (MDSC) which are the putative progenitors in the peripheral blood of TAM in 68 FL pts treated with R-CHOP who have had follow-up for at least 30 months. Methods: Circulating levels of MDSC identified as CD34+, CD45+, CD116+, CD13+, CD14- were evaluated by flow cytometry. Immuno-histochemistry for CD68 was performed on tissue sections. PFS and OS were calculated according to the Kaplan-Meier method. Results: 33 male, 35 female, mean age 56.1 years (20 FL grade 1; 32 grade 2, 16 grade 3A) were included in the analysis. All pts. were treated with R-CHOP in the front line (46/68) or the first relapse (22/68) and all pts. received R for the first time. The analysis of the circulating levels of MSDC showed two different patterns. 40/68 pts had higher levels of circulating MDSC when compared to 30 healthy controls (mean 3.91/mmc vs 1.60/mmc, p= 0.0001) coinciding with high amounts of TAM, 28/68 pts had lower MDSC levels (mean 1.71/mmc) which were correlated to a low number of TAM. The median PFS was not reached for pts. with high MDSC absolute count compared with 21 months for pts. with lower circulating MDSC. A trend towards a better OS at 30 months was also observed for pts. with high MDSC content (OS, 97% versus 92%). Conclusions: Our findings favor the hypotesis that macrophages may act synergically with anti-CD20 targeted therapy perhaps enhancing the antibody-dependent cellular cytotoxicity of R. Furthermore, this mechanism could explain the diminished beneficial effect of rituximab in pts. with low MDSC.
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