Pediatr Blood Cancer Association of Projected Transfusional Iron Burden With Treatment Intensity in Childhood Cancer Survivors Kathleen S. Ruccione, MPH, RN, CPON, FAAN, 1,2,3 Kiran Mudambi, BA, 1,2 Richard Sposto, PhD, 2,4 Joy Fridey, MD, 5,6 Suzy Ghazarossian, DHEd, MT(ASCP) SBB(ASCP)CM, 5,6 and David R. Freyer, DO, MS 1,2,3 * INTRODUCTION Anemia 1 [1] is common during treatment for many forms of childhood cancer. Its symptoms compound suffering and diminish quality of life. In addition, anemia may complicate effective cancer therapy and negatively affect survival [2]. Packed red blood cell (PRBC) transfusions to treat anemia are a mainstay of supportive care for childhood cancer patients and have contrib- uted to improved survival [3]. However, relatively little is known about the long-term consequences of multiple PRBC transfusions in this population. One concern is that PRBC transfusions can disrupt iron homeostasis and result in the accumulation of iron in many organ tissues (iron overload) [4]. Preliminary evidence for transfusional iron overload in pediat- ric oncology patients has been reported in eight publications [5–12]. Most of these represent relatively small single-institution studies and case reports utilizing various methods of direct tissue iron measurement in patients diagnosed with acute leukemia. In the two largest studies, one of 30 children with acute lymphoblas- tic leukemia (ALL) [9] and the other of 25 children with acute leukemia and some solid tumors [12], evidence of liver iron overload was documented in many and correlated with greater PRBC volumes. In addition to the other reports arising from direct tissue iron assessments, estimated total body iron was calculated in a recent study of 107 children with ALL on the basis of PRBC transfusions received, and was found to be associated with leukemia risk group [11]. All reports known to us of iron overload in childhood cancer patients are summarized in Supplemental Table I. While the aforementioned studies are valuable in suggesting that transfusion-related iron accumulation may occur during childhood cancer treatment, they included only a few patients treated for solid tumors, and most have not systematically assessed what other factors, including treatment intensity, might influence risk for developing iron overload. Therefore, we designed this study with the following major objectives: (1) To determine PRBC transfusion volumes administered during treat- ments of varied intensity for several forms of childhood cancer; and (2) to project the estimated total body iron burden on the basis of transfusion volumes received. We have also explored the effects of other host- and treatment-related factors on these outcomes. METHODS This retrospective cohort study was approved by the Children’s Hospital Los Angeles (CHLA) Committee on Clinical Investiga- tions prior to data collection. Subjects in this study were treated at Background. Packed red blood cell (PRBC) transfusion is a mainstay in childhood cancer treatment, but has potential for in- ducing iron overload. The purpose of this study was to determine whether treatment intensity is predictive of projected iron burden resulting from PRBC transfusions among survivors of several forms of childhood cancer. Procedure. This retrospective cohort study involved patients treated at Children’s Hospital Los Angeles (CHLA) between June 1, 2004 and December 31, 2009. Clinical/ demographic data were abstracted from medical records. Treatment Intensity Level was determined for each patient using a published scale. Adjusted cumulative PRBC transfusion volume for each pa- tient (ml/kg) was used to compute the adjusted total iron burden (mg/kg) based upon the average hematocrit of the product. Results. Median age of the cohort (n ¼ 214) was 7.9 years (range 0.2–20.2). One hundred and fourteen (53.3%) were male and 129 (60.3%) were Hispanic/Latino. Diagnoses included acute leukemia and six solid tumors, management of which represents a range of cancer treatment intensities. The number of transfusions, transfusion vol- umes, and projected iron burden were significantly increased and exceeded upper limits of normal among patients with higher treat- ment intensity. Multivariate analysis found younger age and lower hemoglobin at diagnosis to be associated with greater iron burden after adjusting for treatment intensity. Conclusion. Greater treat- ment intensity is associated with need for more PRBC transfusions, and thus increased risk of iron overload among childhood cancer survivors. Iron overload may represent another clinically significant late effect following childhood cancer treatment. Pediatr Blood Cancer ß 2011 Wiley Periodicals, Inc. Key words: blood transfusions; childhood cancer; iron overload Additional supporting information may be found in the online version of this article. 1 LIFE Cancer Survivorship & Transition Program, Keck School of Medicine, University of Southern California, Los Angeles, California; 2 Children’s Center for Cancer and Blood Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California; 3 Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; 4 Department of Preven- tive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; 5 Transfusion Service Center, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California; 6 Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California Conflict of interest: Nothing to declare. *Correspondence to: David R. Freyer, DO, MS, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, 4650 Sunset Boulevard, Mailstop 54, Los Angeles, CA 90027. E-mail: dfreyer@chla.usc.edu Received 6 October 2011; Accepted 18 November 2011 1 Current guidelines for assessment of anemia from the Children’s Oncology Group (COG) state that red blood cell mass should be ade- quate to maintain oxygen carrying capacity and tissue oxygen delivery, for which hemoglobin >7 g/dl is usually adequate, thus defining ane- mia as hemoglobin <7 g/dl. ß 2011 Wiley Periodicals, Inc. DOI 10.1002/pbc.24046 Published online in Wiley Online Library (wileyonlinelibrary.com).