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Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

ABSTRACT: We evaluated whether vitamin D insufficiency (VDI; 25(OH)D <20?ng/ml) was associated with adverse outcomes among follicular lymphoma (FL) patients using an observational prospective cohort study of 642 FL patients enrolled from 2002-2012. The median age at diagnosis was 60 years. At a median follow-up of 59 months, 297 patients (46%) had an event (progression, treatment failure), 78 had died and 42 (6.5%) had a lymphoma-related death. VDI was associated with inferior event-free survival (EFS) at 12 months (EFS12, odds ratio (OR)=2.05; 95% confidence interval (CI) 1.18-3.54), overall survival (OS, hazards ratio (HR)=2.35; 95%CI 1.37-4.02), and lymphoma-specific survival (LSS, HR=2.97; 95% CI 1.52-5.80) for the full cohort. Among patients treated with immunochemotherapy (IC), VDI was associated with inferior EFS12 (OR=3.00; 95% CI 1.26-7.13), OS (HR=2.86; 95% CI 1.39-5.85), and LSS (HR=2.96; 95% CI 1.29-6.79). For observed patients, VDI was associated with inferior OS (HR=2.85; 95% CI 1.20-6.76). For other therapies, VDI was associated with inferior OS (HR=3.06; 95% CI 1.01-9.24). Our work is the first to reveal an association of VDI with early clinical failure, and to demonstrate an association of VDI with adverse outcomes among patients who are observed or treated with therapies other than IC. Our findings suggest a potentially modifiable prognostic factor to address in patients with FL.

SUBMITTER: Tracy SI

PROVIDER: S-EPMC5596381 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

Tracy S I SI Maurer M J MJ Witzig T E TE Drake M T MT Ansell S M SM Nowakowski G S GS Thompson C A CA Inwards D J DJ Johnston P B PB Micallef I N IN Allmer C C Macon W R WR Weiner G J GJ Slager S L SL Habermann T M TM Link B K BK Cerhan J R JR

Blood cancer journal 20170825 8

We evaluated whether vitamin D insufficiency (VDI; 25(OH)D <20 ng/ml) was associated with adverse outcomes among follicular lymphoma (FL) patients using an observational prospective cohort study of 642 FL patients enrolled from 2002-2012. The median age at diagnosis was 60 years. At a median follow-up of 59 months, 297 patients (46%) had an event (progression, treatment failure), 78 had died and 42 (6.5%) had a lymphoma-related death. VDI was associated with inferior event-free survival (EFS) at ...[more]

PMID: 28841207

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Project description:The pathogenesis of follicular lymphoma is a multi-hit process progressing over many years through the accumulation of numerous genetic alterations. Besides the hallmark t(14;18), it is still unclear which other oncogenic hits contribute to the early steps of transformation and in which precursor stages these occur. To address this issue, we performed high-resolution comparative genomic hybridization microarrays on laser-capture micro-dissected cases of follicular lymphoma in situ (n=4), partial involvement by follicular lymphoma (n=4), and duodenal follicular lymphoma (n=4), assumed to represent, potentially, the earliest stages in the evolution of follicular lymphoma. Cases of reactive follicular hyperplasia (n=2), uninvolved areas from follicular lymphoma in situ lymph nodes, follicular lymphoma grade 1-2 (n=5) and follicular lymphoma grade 3A (n=5) were used as controls. Surprisingly, alterations involving several relevant (onco)genes were found in all entities, but at significantly lower proportions than in overt follicular lymphoma. While the number of alterations clearly assigns all these entities as precursors, the pattern of partial involvement by follicular lymphoma alterations was quantitatively and qualitatively closer to that of follicular lymphoma, indicating significant selective pressure in line with its faster rate of progression. Among the most notable alterations, we observed and validated deletions of 1p36 and gains of the 7p and 12q chromosomes and related oncogenes, which include some of the most recurrent oncogenic alterations in overt follicular lymphoma (TNFRSF14, EZH2, MLL2). By further delineating distinctive and hierarchical molecular and genetic features of early follicular lymphoma entities, our analysis underlines the importance of applying appropriate criteria for the differential diagnosis. It also provides a first set of candidates likely to be involved in the cascade of hits that pave the path of the various progression phases to follicular lymphoma development.

Dataset Information

Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

Publications

Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma.

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