Lab Indicators of Iron Level in Bone Marrow Aspirate of Patients Diagnosed with Multiple Myeloma
Authors: Mangla Ankit , Swarup Sriman , Mushtaq Muhammad Umair , Hamad Hussein , Khurana Sharad , Udayagiri Venkata Sravani , Messinger Marina , Catchatourian Rose 
Published: October 2019

Abstract
Introduction
Iron plays a critical role in patients with multiple myeloma (MM). The limited availability of iron to the developing erythroid precursors results in the characteristic anemia so frequently seen in these patients. Moreover, iron is also a determinant in growth of the malignant plasma cells that makes it one of the critical factors in progression of the disease. Iron is a key component in success of erythropoietin (EPO) therapy that is often used to maintain hemoglobin (Hb) level of >10g/dL in patients with MM. International Myeloma working group (2011) advised transfusing IV iron to aid in success of EPO therapy. However, apart from determining the iron stores on bone marraow aspirate, there is hardly any reliable clinical or lab indicator of the iron stores in the body. The utility of various iron indices in determining the bone marrow iron stores remains anecdotal. In this study we aim to determine the relation between iron indices and iron level in the bone marrow of patients diagnosed with multiple myeloma.
Methods
A total of 268 multiple myeloma patients, diagnosed from 2004 to 2015, were identified from tumor registry of John H. Stroger Jr. Hospital of Cook County, Chicago. Accuracy of ferritin, iron level, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and transferrin saturation (TSAT) was evaluated using receiver operating characteristic curves (ROC). Out of sampled patients, 167 patients had a concurrent bone marrow biopsy and aspirate, serum ferritin and iron panel, and were included in ROC analyses.
Results
The study population consisted of 57% African-Americans, 18% Caucasians and 16% Hispanics. Median age was 61 years and 51% were females. Past history was significant for hypertension (48%), diabetes (31%), co-existing inflammatory conditions (18%), smoking (25%), alcohol abuse (17%) and illicit drug abuse (8%). Median hemoglobin, mean corpuscular volume (MCV), leukocytes and platelets were 10g/dL, 90.3fL, 6,200/mcL and 219,500/mcL respectively. Bone marrow aspirates for iron were rated as absent (37%), mild/moderate (18%) and adequate/normal (45%). Anemia was found in 79% of males (Hb <12.9g/dL) and 76% of females (Hb<11.7 g/dL). Of the patients with anemia, 36% of males and 39% of females had absent iron stores (determined by prussian blue staining method) on bone marrow aspirate. MCV was not significantly related with iron deficiency. Iron level, TIBC, UIBC and TSAT were not significantly associated with bone marrow iron (P>0.05). Only ferritin was significant predictor of iron deficiency and presence of iron in bone marrow (AUC 0.64, 95%CI 0.55-0.74, P=0.002). Ferritin levels of ≤15mcg/L (positive LR 3.77, sensitivity 3.4%, specificity 99.1%), ≤30mcg/L (positive LR 2.59, sensitivity 11.9%, specificity 95.4%) and ≤50mcg/L (positive LR 4.35, sensitivity 32.2%, specificity 92.6%) predicted iron deficiency. Ferritin levels of ≥100mcg/L (positive LR 1.47, sensitivity 76.9%, specificity 47.5%), ≥200mcg/L (positive LR 1.46, sensitivity 54.6%, specificity 62.7%) and ≥500mcg/L (positive LR 1.94, sensitivity 23.1%, specificity 88.1%) ruled out iron deficiency.
Conclusion
Of all the indices predicting iron deficiency, only ferritin was significantly associated with absent iron in bone marrow aspirates. In MM patients, iron supplementation should be considered with ferritin levels of ≤50mcg/L and can be deferred with ferritin levels of ≥500mcg/L. Further studies are needed to explore the association.

Disclosures
No relevant conflicts of interest to declare.