Phlebotomy for Pediatric and Young Adult Oncology Patients Treats Transfusional Iron Overload
Authors: Schloemer Nathan , Acquazzino Melissa , Phelan Rachel , Schmidt Debra , Anderson Lynnette , Steffes Sandra , Tower Richard L. , Scott J. Paul 
Published: April 2021

Abstract
Introduction:
Pediatric and young adult oncology patients treated with intense chemotherapy and stem cell transplant regimens have a high incidence of transfusional iron overload.(Acquazzino and Schloemer et al, ASH 2015). Iron deposition can lead to significant complications including heart failure, arrhythmias, liver abnormalities, endocrine dysfunction and ineffective erythropoiesis, as well as increased cancer and mortality risk. However there is a paucity of data regarding recommendations for management of transfusionial iron overload in childhood cancer survivors. Consequently, long-term complications of transfusional iron overload specific to pediatric cancer survivors have not been assessed. We have instituted screening and phlebotomy based treatment algorithms for pediatric and young adult oncology patients with transfusional iron overload.
Methods:
We conducted a retrospective chart review of pediatric and young adults who after having completed oncology management, were diagnosed with transfusional iron overload through a screening algorithm, and then initiated phlebotomy treatment. Tiered screening occurred in patients who received at least 5 packed red blood cell (pRBC) transfusions. Patients were recommended for further evaluation and discussion of possible phlebotomy treatment if they had: (1) liver iron concentration (LIC) greater than 5 mg of iron/gram dry weight liver tissue as measured by ferriscan and/or (2) cardiac MRI T2* &lt; 20 ms. Management of phlebotomy treatment was conducted according to Table 1. During phlebotomy patient iron status was assessed at least quarterly and phlebotomy discontinued with achievement of LIC &lt;5 or normalization of ferritin and followed by imaging LIC assessment verification. Inclusion criteria: (1) diagnosis of childhood malignancy, (2) completed active cancer therapy, (3) received phlebotomy treatment for transfusional iron overload. Exclusion criteria included: Patients with known hereditary hemochromatosis and patients who received photopheresis. Descriptive statistics were employed to report the characteristics of the study population. Spearman correlations were utilized to describe the association between number of transfusions, LIC, ferritin, iron saturation and number of phlebotomy sessions. This study was approved by the Children's Hospital of Wisconsin Institutional Review Board prior to data collection.
Results:
Patient Demographics: We identified 25 pediatric and young adult childhood cancer survivors who underwent phlebotomy for transfusional iron overload. The mean age was 11.6 years (SD 6.1) and 10 (40%) were female. Oncologic diagnoses included ALL (36%), AML (8%), NHL (12%), Ewing sarcoma (16%), Osteosarcoma (4%), Neuroblastoma (12%) and CNS malignancies (12%).
Transfusions/Phlebotomy/Diagnostic Tests: (Table 2) Patients received a median of 25.0 (IQR 17 - 34) pRBC transfusions. No patient had fewer than 10 transfusions. Median number of phlebotomy sessions was 6 (IQR 4-8) occurring over a median period of 0.36 years (IQR 0.28 - 0.59). Prior to phlebotomy, the median LIC was 7.5 mg/g (IQR 5.6-9.0) and median ferritin was 1110.0 ng/mL (IQR 700 - 2030). No patients demonstrated cardiac transfusional iron overload on T2* MRI (n=18). 23 (92%) patients have completed phlebotomy. One patient discontinued phlebotomy due to inability to safely obtain vascular access and no patients developed iron deficiency anemia. LIC was reduced by a median of 2.4 mg/g (IQR 1.1 - 3.6) and ferritin was reduced by median of 586 ng/mL (IQR 366-875). Correlation between number of transfusions received and phlebotomy sessions administered was poor (R2=0.017).
Conclusions:
Management guidelines are absent for transfusional iron overload in pediatric and young adult survivors of cancer. We demonstrate a phlebotomy algorithm that is an effective and well tolerated treatment for pediatric and young adult oncology patients with therapy related transfusional iron overload. Correlation between number of transfusions received and phlebotomy treatments required to remove deposited iron was poor necessitating serial assessments of iron status. Using this management algorithm, prospective studies can evaluate the effect of excess iron removal on iron overload complications in pediatric and young adult cancer survivors.

Disclosures
No relevant conflicts of interest to declare.