Iron Deficiency Anemia Associated with Extracorporeal Photophoresis: A Retrospective Analysis
Authors: Kuhn Alexis K , Merten Julianna A , Bartoo Gabriel T , Dierkhising Ross A , Winters Jeffrey L. , Patnaik Mrinal M , Gastineau Dennis A. , Adamski Jill 
Published: October 2019

Abstract

Since its emergence as a novel therapy for cutaneous T-cell lymphoma in 1987, extracorporeal photopheresis (ECP) has gained popularity in the fields of solid organ and stem cell transplantation (Perotti et al Transfus Apher Sci 2015). Though ECP is thought to be associated with few adverse effects, we have anecdotally noted that some patients treated with ECP develop iron deficiency anemia. Anemia has been reported in ECP literature at an incidence of anywhere from 0% to 24.5%, however, the etiology of the anemia has not been described (Quaglino et al Int J Dermatol 2013, Flowers et al Blood 2008, Jaksch et al J Heart Lung Transpl 2012, Dignan et al Bone Marrow Transpl 2014). We performed a retrospective chart review to further investigate the magnitude of this potential adverse effect.
Adult patients receiving ECP for any indication at Mayo Clinic Hospital-Rochester were eligible for inclusion. Patients with pre-existing iron deficiency anemia (IDA) or physiologic and/or pharmacologic reasons for altered iron homeostasis were excluded from analysis. The primary endpoint was to describe the cumulative incidence of IDA at one year of ECP therapy, utilizing Kaplan-Meier methodology. We defined IDA as a hemoglobin < 12 g/dL (females) or < 14 g/dL (males), plus any of the following: MCV < 80 fL, ferritin < 11 mcg/L, iron < 35 mcg/dL (females) or < 50 mcg/dL (males), total iron binding capacity > 400 mcg/dL, or percent saturation <14%. Secondarily, we aimed to describe the proportion of patients who underwent further diagnostic evaluation of IDA and those that were initiated on iron supplementation for IDA. Patients were followed for the primary endpoint until diagnosis of IDA, death, or date of last ECP session; those who did not develop IDA were censored at the date of last follow-up.
Between January 1, 2006 and July 1, 2015, a total of 120 adult patients were treated with ECP at Mayo Clinic in Rochester, MN; 80 patients met inclusion criteria. For the remaining 40 patients, patients were excluded for recent history of transfusions and/or phlebotomy (n=27), incomplete documentation (n=7), IDA at baseline (n=3), or potentially confounding past medical histories (n=3). Treatment of graft-versus-host disease (GVHD) was the foremost ECP indication in our cohort, accounting for 63.8% of our patients. Patients also received ECP for treatment of cutaneous T-cell lymphoma, treatment of solid organ transplant rejection, and other indications (25%, 7.5%, and 3.8%, respectively). Mean age was 55.6 years, 38.7% were female, and the median duration of ECP therapy was 344 days (IQR 130 - 755 days).
At 1 year from the start of ECP therapy, the cumulative incidence of IDA in our cohort was 21.1% (95% CI 9% - 31.6%; Figure 1). At 4 years from the start of ECP therapy, the cumulative incidence of IDA was 49.1% (95% CI 26.4% - 64.8%). Of those that developed an IDA at any time during ECP therapy, 6/20 (30%) underwent invasive diagnostic procedures (colonoscopy and/or upper endoscopy) to evaluate the etiology of the IDA. Iron supplementation was initiated in 18/20 (90%) patients; hemoglobin returned to normal in 8 patients (44.4%) based on available follow-up. These data indicate that a substantial number of patients develop IDA while receiving ECP therapy; a finding which may lead to more prompt recognition and treatment of IDA in patients receiving ECP, and perhaps spare expensive diagnostic procedures.
Figure 1. Kaplan-Meier Curve of Cumulative Incidence of IDA During ECP Therapy Figure 1. Kaplan-Meier Curve of Cumulative Incidence of IDA During ECP Therapy

Disclosures
No relevant conflicts of interest to declare.