Functional Iron Deficiency Anemia Research Articles

Intravenous Iron Monotherapy for Absolute and Functional Iron Deficiency Anemia in Cancer Patients

AbstractAbstract 5167 ObjectiveIron deficiency anemia (IDA) is common in cancer patients. The Hemoglobin (Hb) response rate in cancer patients with IDA who receive an erythropoiesis stimulating agent (ESA) ranges from 25 – 65% and is increased to 68 – 93% when intravenous (IV) iron is added to the ESA. Interestingly, there have been no studies to date that have evaluated Hb response to IV iron monotherapy for the treatment of IDA in cancer patients. The National Comprehensive Cancer Network (NCCN) recommends treating absolute IDA (AIDA, serum ferritin < 30 ng/mL and TSAT < 15%) with iron monotherapy, preferably IV. However, the NCCN recommends that functional IDA (FIDA, serum ferritin ≤ 800 ng/mL and TSAT < 20%) be treated with both IV iron plus an ESA. Unfortunately, ESAs carry black box warnings for increased mortality, cancer progression, and venous thromboembolism. Therefore, it is important to explore other ways to more safely treat IDA in cancer patients. The objective of this study was to evaluate the Hb response rate to IV iron monotherapy in cancer patients with AIDA and FIDA. MethodsA retrospective chart review was performed at the Huntsman Cancer Institute between January 2006 and June 2011 in cancer patients with AIDA or FIDA who were treated with low molecular weight iron dextran (LMWID) monotherapy. Patients were excluded if they had a ferritin > 800 ng/mL or TSAT ≥ 20%, received an ESA within 6 weeks prior to or within 4 weeks after the LMWID infusion, or received a packed red blood cell transfusion prior to the LMWID infusion without a documented post- transfusion, pre-LMWID infusion Hb. The primary outcome was the proportion of patients with a Hb response defined as an increase of at least 1 g/dL within 6 weeks post IV iron infusion. The secondary outcome was the Hb response within 6 weeks stratified by dose of IV iron. ResultsTwo hundred patients received LMWID at our institution within the specified time period. However, 182 patients were excluded because they did not have active cancer, did not have a definitive diagnosis of AIDA or FIDA, or received concomitant therapy with an ESA. Eighteen patients with either a hematologic or solid malignancy were included. Thirteen patients had AIDA and 5 patients had FIDA. Eight of the 13 (62%) patients in the AIDA group had a Hb response. The median Hb increase in the AIDA group was 1. 3 g/dL (p < 0. 0001). A Hb response was observed in 4 of the 5 (80%) patients in the FIDA group. The median Hb increase in the FIDA group was 1. 8 g/dL (p = 0. 0224). Of the 8 patients with AIDA achieving a response, 4 received less than and 4 received more than the calculated total IV iron dose (equation per package insert). Of the 4 patients achieving a Hb response in the FIDA group, 3 received less than and 1 received equal to the calculated total dose. The overall Hb response rate to IV iron monotherapy for both groups was roughly 67% which is greater than the Hb response rate reported with ESAs alone. See Table 1 for individual patient details. ConclusionAlthough our study has limited patient numbers, this is the first data suggesting that IV iron without an ESA may be an effective treatment for both AIDA and FIDA in anemic patients with a variety of malignancies. IV iron monotherapy may eliminate the need for an ESA. This hypothesis should be tested in larger studies.Table 1:Individual Patient Baseline Demographics and Hb ChangeType of CancerFerritin (ng/mL)TSAT (%)Baseline Hb (g/dL)LMWID dose (gm) infusedCalculated LMWID dose (gm)% of TDI givenHb (g/dL) ≤ 6 weeksHb (g/dL) ChangeAbsolute IDAColorectal1548.821.314512.2+3.4Plasmacytic lymphoma2647.4221008.3+0.9GIST1049.211.56310.5+1.3MM12611.711.46812.3+0.6DLBCL1869.22.2211310.5+1.3MM961211.56811.7-0.3CMML2278.621.216410.9+2.3MM1098.60.823910.4+1.8Inflammatory breast1849.621.315411.3+1.7NSCLC1858.4221009.1+0.7Esophageal1039.611.75812+2.4NSCLC2249.111.85410.9+1.8Colorectal2957.61.12.3478.5+0.9Functional IDACMML4159.51.51.88611.4+1.9Bladder1356101110011.4+1.4Esophageal1981110.111.8579.9-0.2Rectal152199.311.75911.1+1.8MM62159.30.81.94212.7+3.4CMML = chronic myelomonocytic leukemia, DLBCL = diffuse large b-cell lymphoma, GIST = gastrointestinal stromal tumor, Hb = hemoglobin, LMWID = low molecular weight iron dextran, MM = multiple myeloma, NSCLC = non-small cell lung cancer. Disclosures:Off Label Use: The total dose infusion of low molecular weight iron dextran is not an FDA approved dosing regimen. However, it is commonly used in practice and has been used in other studies. Rodgers:American Regent: Consultancy.

ORIGINAL ARTICLE: RET‐Y and RBC‐Y in the diagnosis of iron deficiency associated with anaemia of inflammation

SummaryWe evaluated the usefulness of RET‐Y and RBC‐Y in distinguishing functional iron deficiency from iron‐deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET‐Y and RBC‐Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC‐Y and RET‐Y values in iron‐deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P &lt; 0.001). The mean level of RET‐Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET‐Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC‐Y. Receiver operating characteristic analysis also showed lower specificity for RBC‐Y and RET‐Y compared with that of sTfR and its log ferritin ratio (F‐index). RET‐Y and RBC‐Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.

Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesis.

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.