Characterization of B12 Deficiency in Patients with Plasma Cell Disorders

Background:

Although vitamin B12 deficiency has been reported in patients with plasma cell dyscrasias (PCDs), no mechanism has been identified. Excess free light chains (FLCs), readily measurable by the serum FLC assay since 2001, could disrupt the renal proximal tubule receptors megalin and cubulin where B12 is reabsorbed. We sought to identify risk factors for B12 deficiency in PCD patients to elucidate a possible mechanism. In particular, we hypothesized that rates of B12 deficiency would be higher in PCD patients with higher FLC burdens.

Methods:

Of 1482 patients with ICD9 codes for PCDs, 530 met the inclusion criteria of having both serum B12 and FLC values. We reviewed the electronic medical records to obtain clinical data collected in the time preceding the patient's lowest B12 level. Patients were excluded if the lowest B12 was elevated in the setting of known concurrent vitamin B12 replacement therapy.

Data from eligible patients were analyzed using chi-square, Student's independent t test, and Spearman's rank-order correlation to identify associations between B12 insufficiency (defined as <250 pg/ml or <350pg/ml and B12 treatment history) and PCD characteristics. This retrospective study was approved by the Mount Sinai IRB.

Results:

Overall, 26.6% patients were found have vitamin B12 insufficiency. Other than an IgG isotype PCD (P=0.025) there were no significant differences in age, gender, or PCD diagnosis between patients with and without B12 insufficiency (see Table 1).

As expected, there was a strong negative correlation between eGFR and involved FLC, r(248) = -0.277, p < 0.001. However, unexpectedly, there was also a significant negative correlation between B12 level and eGFR, r_s(487) = -0.106, p = 0.019 such that insufficient B12 was associated with normal eGFR (p = 0.001). There was no correlation between B12 level and involved FLC (p = 0.948) nor B12 level and Bence Jones proteinuria (p = 0.302).

Discussion:

While our data do not appear to support the proposed mechanism of FLC disruption of renal receptors, B12 deficiency was more common in our sample (26.6%) than the previously reported 13.6% prevalence among PCD patients (Baz et al Cancer 2004). While B12 deficiency and PCDs are both associated with higher age, the prevalence of B12 deficiency among older adults is only 10-15% (Baik et al Annu Rev Nutr 1999). Therefore, prospective studies are needed to explore other characteristics of PCD patients, such as chemotherapy treatment (Tandon et al Indian Pediatr 2015) or aspirin use (van Oijen et al Am J Cardiol 2004), contributing to a high prevalence of B12 deficiency in this population. Detection and treatment of B12 deficiency among PCD patients remains clinically important to reduce ensuing sequelae of neurologic dysfunction and cytopenias, which are complications of PCDs and their treatments.