VITAMIN D DEFICIENCY IMPAIRS RITUXIMAB-MEDIATED CELLULAR CYTOTOXICITY

To investigate the impact and underlying mechanisms of vitamin D-deficiency (VDD) on the outcome of elderly (61 to 80 years) patients with diffuse large B-cell lymphoma (DLBCL), we measured 413 pretreatment 25-OH-vitamin D serum levels from 2 trials (RICOVER-60 and RICOVER-noRTh) by a commercially a...

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Veröffentlicht in:Anticancer research 2014-04, Vol.34 (4), p.2049-2049
Hauptverfasser: Bittenbring, Jorg Thomas, Neumann, Frank, Altmann, Bettina, Achenbach, Marina, Ziepert, Marita, Reichrath, Jorg, Held, Gerhard, Pfreundschuh, Michael
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container_issue 4
container_start_page 2049
container_title Anticancer research
container_volume 34
creator Bittenbring, Jorg Thomas
Neumann, Frank
Altmann, Bettina
Achenbach, Marina
Ziepert, Marita
Reichrath, Jorg
Held, Gerhard
Pfreundschuh, Michael
description To investigate the impact and underlying mechanisms of vitamin D-deficiency (VDD) on the outcome of elderly (61 to 80 years) patients with diffuse large B-cell lymphoma (DLBCL), we measured 413 pretreatment 25-OH-vitamin D serum levels from 2 trials (RICOVER-60 and RICOVER-noRTh) by a commercially available chemoluminescent immunoassay (DiaSorin, LIASON). The 359 RICOVER-60 patients with VDD (defined as serum levels < or =8 ng/ml, determined by an exploratory analysis) and treated with rituximab had a 3-year event-free survival of 59% compared to 79% in patients with vitamin D levels >8 ng/ml; 3-year overall survival was 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for event-free and 1.9 (p=0.040) for overall survival. These results were confirmed in an independent validation set of 63 patients from the RICOVER-noRTh study. An explanatory mechanism may be impaired Rituximab-mediated cellular cytotoxicity (RMCC) in VDD individuals. RMCC was determined by LDH release assay of CD20+ Daudi cells attacked by NK-cells. In otherwise healthy volunteers with VDD (8.4+ or -3.0 ng/ml) substituted to normal values (40.6+ or -13.6 ng/ml) the RMCC increased significantly (p
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The 359 RICOVER-60 patients with VDD (defined as serum levels &lt; or =8 ng/ml, determined by an exploratory analysis) and treated with rituximab had a 3-year event-free survival of 59% compared to 79% in patients with vitamin D levels &gt;8 ng/ml; 3-year overall survival was 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for event-free and 1.9 (p=0.040) for overall survival. These results were confirmed in an independent validation set of 63 patients from the RICOVER-noRTh study. An explanatory mechanism may be impaired Rituximab-mediated cellular cytotoxicity (RMCC) in VDD individuals. RMCC was determined by LDH release assay of CD20+ Daudi cells attacked by NK-cells. 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