Lifetime Transfusion Burden and Transfusion-Related Iron Overload in Adult Survivors of Solid Malignancies

Abstract

Background: Limited data exist on transfusion burden and transfusion-related iron overload in adult survivors of solid malignancies.

Methods: Hospital-specific cancer registry data of patients with solid tumor receiving systemic anticancer treatment between January 2008 and September 2009 at the Oncology Department of the Leiden University Medical Center (The Netherlands) were retrieved and cross-referenced with red blood cell (RBC) transfusion records. Individual lifetime transfusion burden was captured in April 2015. Multitransfused long-term survivors with serum ferritin >500 μg/L were subsequently screened for hepatic and cardiac iron overload using 1.5 Tesla magnetic resonance imaging.

Results: The study population consisted of 775 adult patients with solid cancer (45.2% male; median age, 58 years; >75% chemotherapy-treated), 423 (54.6%) of whom were transfused with a median of 6.0 RBC units (range 1-67). Transfusion triggers were symptomatic anemia or hemoglobin <8.1-8.9 g/dL prior to each myelosuppressive chemotherapy cycle. We identified 123 (15.9%) patients across all tumor types with a lifetime transfusion burden of ≥10 RBC units. In the absence of a hemovigilance program, none of these multitransfused patients was screened for iron overload despite a median survival of 4.6 years. In 2015 at disclosure of transfusion burden, 26 multitransfused patients were alive. Six (23.1%) had hepatic iron overload: 3.9-11.2 mg Fe/g dry weight. No cardiac iron depositions were found.

Conclusion: Patients with solid malignancies are at risk for multitransfusion and iron overload even when adhering to restrictive RBC transfusion policies. With improved long-term cancer survivorship, increased awareness of iatrogenic side effects of supportive therapy and development of evidence-based guidelines are essential.

Implications for practice: In the presence of a restrictive transfusion policy, ∼30% of transfused adult patients with solid cancer are multitransfused and ∼50% become long-term survivors, underscoring the need for evidence-based guidelines for the detection and management of transfusion-related iron overload in this group of patients. In each institution, a hemovigilance program should be implemented that captures the lifetime cumulative transfusion burden in all patients with cancer, irrespective of tumor type. This instrument will allow timely assessment and treatment of iron overload in cancer survivors, thus preventing organ dysfunction and decreased quality of life.

Keywords: Bone neoplasms; Erythrocyte transfusion; Iron overload; Long-term survivors; Neoplasms; Solid tumor; Testicular neoplasms; Toxicity.

Figure 1

Distribution of cancer types in red blood cell (RBC) transfused patients. The left pie chart shows that RBC transfusions were administered across all cancer types. The right pie chart shows that multitransfused patients could be identified among all cancer types with the exception of head and neck cancers (). A relatively large proportion of patients with bone tumors () was multitransfused.

Figure 2

Lifetime RBC transfusion burden of all 775 patients grouped according to anticancer treatment received at inclusion. Subsets were defined as follows: single or multiagent chemotherapy regimen (52.1% transfused), concomitant chemoradiotherapy or radiotherapy only (61.6% transfused), targeted therapy only (65.0% transfused), miscellaneous systemic treatment only (50.0% transfused), or best supportive care only (72.2% transfused). For the 423 transfused patients, median lifetime transfusion burden was 6.0 RBC units in the CT group (n = 305), 4.0 RBC units in the CRT group (n = 53), 6.0 RBC units in the TT group (n = 39), 4.0 RBC units in the Misc group (n = 13), and 4.0 RBC units in the BSC group (n = 13). Multitransfusion was observed in patients undergoing any type of anticancer treatment. In contrast, none of the patients in the best supportive care group, who did not receive any anticancer treatment, was multitransfused. The majority (84.1%) of patients who received 20 or more RBC transfusions were found in the group of patients treated with chemotherapy. Abbreviations: BSC, best supportive care; CRT, concomitant chemoradiotherapy or radiotherapy only; CT, chemotherapy; Misc, miscellaneous systemic treatment; RBC, red blood cell; TT, targeted therapy.

Figure 3

Evolution of serum ferritin levels in multitransfused survivors during follow‐up. Serum ferritin was measured at the treating physician's discretion and was available at two time points for 21 of 26 multitransfused survivors: end of treatment, which corresponds with the serum ferritin determined immediately after end of anticancer therapy, and at end of follow‐up more than 5 years later in 2015. Median serum ferritin was significantly lower at end of follow‐up (192 μg/L, interquartile range [IQR] 78.5–803.5) than at end of treatment (1,300 μg/L, IQR 332.5–1,733; P = .0004). One patient with metastasis (*) demonstrated a 10‐fold increase in serum ferritin after having received 15 red blood cell units. Abbreviations: EOT, end of treatment; FU, follow‐up.