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Serum Concentrations of Vitamin B-12 and Alkaline Phosphatase in Newly Diagnosed Multiple Myeloma Patients.

Francesca Elice, Maurizio Zangari, Bart Barlogie, Michael J. Burns, Guido J. Tricot, Sara Roberti, Francesco Rodeghiero and R. Jean Hine

Abstract

Background: A controversy about a possible link between vitamin B12 deficiency and multiple myeloma (MM) has persisted since the 1970s. Vitamin B12 (B12) deficiency can cause anemia, neuropathy and has been associated with osteoporosis and reduced bone density. Therefore, B12 deficiency might worsen some clinical symptoms of MM.

Methods: We evaluated serum B12 concentrations in 393 untreated MM patients included in the Myeloma Institute Program (October 1998 to March 2005). Total serum B12 was assessed by using ADVIA Centaur immunoassay with chemiluminescent detection; laboratory B12 deficiency was defined as serum B12 levels < 156 mmol/L. Serum alkaline phosphatase (ALP) was determined by a kinetic rate method. Neuropathy was assessed clinically according to NIH guidelines. Correlations of serum B12 concentrations with bone density (radial T- and Z -score) and thalidomide-related neuropathy were investigated. Categorical variables were compared using chi-square and Fisher’s exact test, while correlation coefficient was used for quantitative variables.

Results: The sample was 57% male, median age = 58 years, stage III 70%, median creatinine 1.0 mg/dL, IgG 52%, IgA 24%, and light chain disease 19%. Prevalence of laboratory B12 deficiency was 3.5%, prevalence of functional deficiency (B12 < 241 mmol/L) was 20.4%. No influence of age or MM isotype on B12 levels was observed. Sixty seven percent (264) of the patients received thalidomide in combination with chemotherapy. Levels of B12 did not affect the development of grade ≥ 2 neuropathy after thalidomide treatment (p=0.49). No significant association was observed between serum B12 and the radial T- and Z score at bone densitometry (n= 270). There was a highly significant correlation between serum B-12 and ALP levels (correlation coefficient 0.25, p < 0.0001).

Conclusions: Laboratory B12 deficiency was not common in our series of newly untreated MM patients. B12 levels did not predict the development of thalidomide-related neuropathy, nor are they associated with reduced bone density. The most striking finding of our study was a highly significant correlation between serum B12 and ALP concentrations; clinical significance of this observation requires further evaluation.