Multiple Packed Red Blood Cell (PRBC) Transfusions In Pediatric Patients With Acute Myeloid Leukemia (AML) Result In a Large Transfusional Iron Dose With The Potential For Long-Term Organ Dysfunction

The treatment of AML in children utilizes intensive chemotherapy and often myeloablative hematopoietic cell transplant (HCT). This results in significant myelosuppression, necessitating blood product transfusions. Repeated PRBC transfusions result in an increase in the body iron load which can lead to secondary hemochromatosis and organ dysfunction, particularly the heart and liver. Patients with hemoglobinopathies on chronic PRBC transfusions require iron chelation therapy usually after 10-20 units transfused. While patients with AML receive multiple transfusions, there is little data on the number or volume of PRBC transfused or the estimate of the iron load received.

This retrospective study evaluated the number and volumes of PRBC transfusions administered to pediatric (<14 years) patients with AML, and calculated an estimate of the iron infused.

Twenty-two patients with AML were diagnosed and treated at our institution between January 2010 and December 2012. There were 13 girls and 9 boys with a median age at diagnosis of 7.5 years (mean 6.95; range 0.4-13.2). One patient died early of sepsis without achieving complete remission (CR), and another died in CR following her last course of chemotherapy. Eight patients underwent HCT following myeloablative conditioning with busulfan, cyclophosphamide and etoposide; the remaining received chemotherapy alone. For patients who completed their chemotherapy the cumulative anthracycline dose was 450 mg/m². Patients received a median of 17.5 PRBC transfusions (mean 16.6; range 3-28) during the course of their treatment. The cumulative PRBC transfusion volume was 185.4 ml/kg (mean 175.8; range 24.87 – 311.58), which translates to a median iron dose of 129.8 mg/kg (mean 123.1; range 17.4 – 218.1). The median serum ferritin level for those patients who were tested (n=12) was 1794.5 mg/L (mean 9074.5; range 699 – 78500). The median projected hepatic iron content, based on the transfused iron burden was 12.24 mg/g liver dry weight (mean 11.61; range 1.64 – 20.58); 17 (77.3%) patients had projected hepatic iron concentrations in excess of 7.0 mg/g, and none were <1.6 mg/g. Ten patients have developed a > 10 percentage point reduction in their left ventricular ejection fraction (LVEF; range -11% to -45%) however only one patient is on cardiac failure medications. Cardiac T2* MRI studies are being conducted to evaluate cardiac iron status for patients in this cohort. 13 patients were alive in CR at a median follow-up duration of 1.83 years (mean 2.16; range 0.27 – 3.43).

Pediatric patients with AML receive large volumes of PRBC transfusions during their treatment and as a consequence accumulate high total body iron. This is in excess of the threshold for chelation therapy, used to prevent organ dysfunction, in patients with hemoglobinopathies. In addition, AML patient also receive significant cardio-toxic medications which may compound the effect of iron on the myocardium. With improvements in long term survival for patients with AML the addition of iron chelation therapy must be studied in order to prevent long term toxicity of AML therapy.