Monitoring and Treatment of Transfusional Iron Overload: Findings from an Electronic Medical Records Review Study at the Moffitt Cancer Center and Research Institute.
Authors: Ray Leslie A , Wetzstein Gene A. , Wang Si-Tien , Guo Amy , Korves Caroline , Clinton Bentley , Wei Robert , Duh Mei S. 
Published: October 2019

Abstract 1503

Purpose:

Patients with red blood cell (RBC) transfusion-dependent conditions are at risk of developing transfusional iron overload (TIO) which can cause organ damage. Iron chelation therapy (ICT) with either oral deferasirox or subcutaneous deferoxamine prevents and limits organ damage in patients with TIO; however, TIO monitoring and ICT utilization in real-world clinical practices are not well characterized.

Methods:

The medical records of adult patients (>18 years) receiving ≥10 RBC units ≥6 months prior to data abstraction were identified from the Moffitt Cancer Center and Research Institute, a comprehensive cancer care center. Data abstraction occurred between 12/2009 and 6/2010. Patients’ observation period spanned from the tenth RBC unit to end of study follow-up (i.e., death, clinic departure or end of observation period). Patients participating in an ICT clinical trial 6 months prior to their tenth RBC unit were excluded. TIO monitoring was defined as receipt of ≥1 serum ferritin test after the tenth RBC unit. ICT-eligibility was defined as ≥2 serum ferritin tests ≥1,000 μg/L or ≥20 RBC units transfused. ICT treatment was defined as ≥1 prescription for deferasirox or ≥1 administration of deferoxamine. Primary study endpoints were the proportion of patients monitored for TIO after ten, twenty, and thirty RBC units and the proportion of ICT-eligible patients who received ICT. Kaplan-Meier and Cox proportional hazards regression methods were used to compare overall survival between TIO-monitored and unmonitored patients, as well as ICT-treated and untreated patients.

Results:

Medical records data for 163 patients receiving ≥10 RBC units were extracted, among which 58.3% and 30.1% went on to receive ≥20 and ≥30 RBC units, respectively. The average observation period was 6.9 (±5.9) months. Average age at transfusion of the tenth RBC unit was 57.8 (±14.1) years and 36.8% were female. Most patients (50.3%) had leukemia as their underlying disease necessitating RBC transfusion, followed by myelodysplastic syndrome (20.2%) and lymphoma (16.6%). Approximately 44.8% of patients receiving ≥10 RBC units, 53.7% of patients receiving ≥20 RBC units, and 67.3% of patients receiving ≥30 RBC units were monitored for TIO. Average serum ferritin levels were 2,714 (±1,970) μg/L (between 10–20 RBC units), 4,156 (±4,932) μg/L (between 20–30 RBC units) and 3,872 (±2,305) μg/L (>30 RBC units), respectively. Compared to those unmonitored for TIO, patients monitored for TIO after 10 RBC units had significantly longer median survival (16.13 vs. 2.30 months; log-rank p-value<0.001). This survival benefit of TIO monitoring was maintained after controlling for age, gender, underlying disease, and total units of RBCs transfused (hazard ratio for TIO-monitored=0.271; p-value<0.001). Among 99 ICT-eligible patients, 56% were monitored for TIO and 9% received ICT. ICT-treated patients had longer median survival than untreated patients (9.48 vs. 7.16 months), although this difference was not significant (log-rank p-value=0.593) likely due to small sample size of treated patients. Results remained the same after adjusting for age, gender, underlying disease, and total units of RBCs transfused. Among the 9 ICT-treated patients, 8 (88.9%) received deferasirox and 1 (11.1%) received deferoxamine. At ICT initiation, patients had received an average of 20.5 (±9.2) RBC transfusions [46.0 (±19.5) RBC units] and the average serum ferritin level was 3,834 (±2,677) μg/L.

Conclusions:

TIO monitoring after 10 RBC units and ICT treatment among ICT-eligible patients may be associated with survival benefits. However, the significance of slightly longer survival associated with ICT treatment could not be assessed due to a small sample size of treated patients. Indeed, only 9% of ICT-eligible patients received ICT, suggesting that TIO may not be sufficiently managed in real-world clinical practice. Even when patients were treated, ICT-initiation occurred at a higher average serum ferritin level than recommended by the National Comprehensive Cancer Network (i.e., >2,500 μg/L). Greater awareness about the risks of TIO is necessary to improve clinical outcomes among transfusion-dependent patients. Finally, since 50% of patients had leukemia as their underlying disease, further research is warranted on the significance and clinical impact of TIO monitoring and treatment specifically among these patients.

Disclosures:

Ray: Novartis Pharmaceuticals Corporation: Research Funding. Wetzstein:Novartis Pharmaceuticals Corporation: Research Funding. Wang:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Guo:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Korves:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Clinton:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Wei:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Duh:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding.