Vitamin D Insufficiency and Prognosis in Non-Hodgkin"s Lymphoma

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Clin Oncol. 2010 Aug 16;[Epub Ahead of Print], MT Drake, MJ Maurer, BK Link, TM Habermann, SM Ansell, IN Micallef, JL Kelly, WR Macon, GS Nowakowski, DJ Inwards, PB Johnston, RJ Singh, C Allmer, SL Slager, GJ Weiner, TE Witzig, JR Cerhan：重庆市中山医院肿瘤科杨志祥
在弥漫大B淋巴瘤和T细胞淋巴瘤中，Vit D不足预示无病生存和总生存期较差。

 

STUDY IN CONTEXT
Vitamin D insufficiency is commonly seen in clinical practice in the United States (25% to 50% of patients). Several reports suggest that low serum levels of 25-hydroxyvitamin D [25(OH)D] may be associated with an increased incidence of colorectal and breast cancer, and possibly non-Hodgkin’s lymphoma (NHL). Other studies have shown an association of low vitamin D with poorer prognosis in colorectal cancer, breast cancer, and multiple myeloma.
To test whether vitamin D levels can predict prognosis in NHL, Drake et al looked at 1691 consecutive patients with newly diagnosed NHL (within 9 months) from the Molecular Epidemiology Resource of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence. Patients were enrolled from 2002 to 2008. Serum samples were drawn within 120 days of diagnosis, and all vitamin D measurements were made by liquid chromatography−tandem mass spectrometry, which is considered the most reliable and accurate test for 25(OH)D levels.

The results showed that 56 (5.7%) of the 983 eligible patients had severe vitamin D insufficiency (<10 ng/mL); 380 (38.7%) had mild-to-moderate insufficiency (10 to 24 ng/mL); and 547 (55.6%) had no deficiency (optimal range, 25 to 80 ng/mL). Thus, 436 patients (44%) were classified as 25(OH)D insufficient (combined severe and mild-to-moderate insufficiency). Median follow-up was 34.8 months (range, 0.5 to 77 months).
Vitamin D sufficiency was significantly associated with poorer prognosis in patients with diffuse large B-cell lymphoma (DLBCL) and T-cell lymphoma (TCL), but not other less aggressive lymphoma subtypes (mantle cell lymphoma, follicular lymphoma, post-follicular lymphoma, and all others). The authors noted that the number of patients in the study with these less aggressive NHL types was small and urged further studies in larger group of these patients.

Of the patients with DLBCL, 52% were vitamin D insufficient, and those patients had significantly inferior event-free survival (EFS) (hazard ratio [HR], 1.67; P = .005) and overall survival (OS) (HR, 2.34; P < .001). After adjustment for International Prognostic Index (IPI) and treatment, the HRs for vitamin D insufficiency continued to be inferior: 1.41 for EFS, 2.16 for lymphoma-specific survival (LSS), and 1.99 for OS.1

Among the patients with TCL, 57% were 25(OH)D insufficient, and these patients had significantly inferior EFS (HR, 2.47; P = .003) and OS (HR, 2.67; P = .01). After adjustment for IPI score, the HRs were 1.94 for EFS, 2.26 for LSS, and 2.38 for OS.
3 m( N9 A7 2 j  w: i7 |0 o0 BThe researchers also addressed the issue of tumor size as a confounding factor in patients with DLBCL and TCL. Larger tumors are associated with increased 1-alpha-hydroxylase activity, which might increase conversion of 25(OH)D to 1,25-dihydroxyvitamin D [1,25(OH)2D], its active metabolite, leading to artificially low 25(OH)D levels. However, there were no differences between 25(OH)D-sufficient and -insufficient patients with these two NHL subtypes in calcium levels or albumin-corrected calcium (a surrogate for tumor activity). Furthermore, measurement of 1,25(OH)2D levels in DLBCL and TCL patients showed an association with low levels and inferior EPS, LSS, and OS.
In summary, low levels of 25(OH)D were associated with inferior EPS, LSS, and OS for patients with DLBCL and TCL. Whether using vitamin D supplements to normalize vitamin D levels in these patients could improve outcomes will require testing in future trials. The authors noted that in TCL, inferior outcomes were seen in both 25(OH)D-insufficient patients (<25 ng/mL) and those at the lower end of the optimal range (25 to 80 ng/mL). Thus, supplementation even for patients within the optimal range might be useful.