Targeted Screening in Pediatric and Young Adult Oncology Patients Identifies Transfusional Iron Overload

Introduction: Pediatric and young adult oncology patients often require supportive red blood cell transfusions throughout their therapy course, which may result in iron overload. Despite this, screening recommendations to identify transfusional iron overload in childhood cancer survivors are lacking.  Iron deposition can lead to end-organ damage and complications including heart failure, arrhythmias, liver abnormalities, endocrine dysfunction, ineffective erythropoiesis, and increased cancer and mortality risk.  Little is known about long-term complications of iron overload in pediatric cancer survivors and treatment guidelines for iron overload in this patient population have not been developed.  We instituted an algorithm to identify pediatric and young adult oncology patients with iron overload and refer them for treatment.

Methods: This quality improvement project identified pediatric and young adult oncology patients for screening of transfusional iron overload, recommended diagnostic testing, and referred those with iron overload (as defined by liver T2* <20) to Hematology for treatment.  Patients screened met the following criteria: 1) treatment for cancer or cancer relapse 2) greater than 10 transfusions and/or greater than 150 ml/kg of packed red blood cells (pRBCs) since the start of our electronic medical record (11/3/2012) and 3) completed treatment or in maintenance therapy for acute lymphoblastic leukemia.  Exclusion criteria included: status less than 100 days post allogeneic hematopoietic stem cell transplantation, in palliative phase of care or receiving therapy for relapsed disease.  Providers were notified of their patients meeting criteria for screening and asked to follow the screening, diagnosis and referral algorithm (Figure 1).  Provider recognition of need for screening and compliance with the algorithm at 6 months after institution were tracked.  Descriptive statistics were used to describe the characteristics of the study population.  Spearman correlations were used to determine the association between number and volume of transfusions, and ferritin and liver T2* results.

Results: Thirty patients were screened for iron overload. The mean age was 10.3 years (SD 7.5), 12 (40%) were female and 17 (57%) had a diagnosis of leukemia or lymphoma.  The median number of transfusions received was 15 (10-47) and the median volume of blood received was 129 mL/kg (33-572).

Thirty-six pediatric and young adult oncology patients were identified for iron overload screening, of whom only 2 (6%) had already received appropriate screening, 4 (11%) had received partial screening and 30 (83%) had received no screening.  After the initial 6 months, 30 of the 34 patients who had undergone no or partial screening completed the recommended algorithm (88% compliance, see Figure 1). Nineteen (95%) of 20 patients with positive screening labs had iron overload by MRI. Fourteen (74%) of 19 patients with iron overload were seen by Hematology and 9/14 (64%) started treatment for iron overload (8-phlebotomy and 1-oral chelation).

Nineteen patients (63%) were diagnosed with iron overload.  The mean age was 11.8 years (SD 7.5), 6 (32%) were female and 12 (63%) had leukemia or lymphoma.  The median number of transfusions received was 18 (10-47) and the median volume of blood received was 139 mL/kg (33-572).  The median ferritin was 942 ng/mL (316-2340), median liver T2* was 6.6 (2.6-12.9) and median cardiac T2* was 26.7 (19.6-36). Number of transfusions (r=-0.79, p<0.0001), volume of blood in mL/kg (r=-0.58, p=0.014) and ferritin (r=-0.51, p=0.023) were strongly associated with liver T2* results (Figure 2). No patients had isolated cardiac iron overload.

Conclusion: Targeted screening of pediatric and young adult oncology patients identified a high percentage of transfusional iron overload. Provider recognition of the need for iron overload screening in this high risk group was poor prior to institution of this quality improvement initiative.  Prospective studies are required to determine if identification and subsequent treatment of transfusional iron overload can alter long-term complications of iron deposition and decrease morbidity of oncology treatment in pediatric and young adult survivors.