Patients receiving chronic extracorporeal photopheresis (ECP) therapy are at risk of developing iron deficiency anemia (IDA), most likely due to retained blood products in the procedure instrument, and should be monitored, according to research published in the Journal of Clinical Apheresis.

ECP is a procedure that influences T-cell activity in patients with immune-mediated cellular damage because of activated lymphocytes. It is approved for use in patients with cutaneous T-cell lymphoma, and has nonapproved indications for graft vs host disease and bronchiolitis obliterans syndrome.

In a retrospective analysis, a team of researchers evaluated the risk of IDA and compared ECP with the newer CELLEX instrument to the older UVAR instrument. They used data from 34 patients receiving ECP from 2015 and 2019 at the Center for Cellular Therapy and Transfusion at Emory University Hospital in Atlanta, Georgia. A total of 13 patients had ECP with the UVAR instrument, and 21 had the procedure with the CELLEX instrument. Both instruments were manufactured by Therakos Inc.

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The authors defined clinical IDA as a decrease in hemoglobin after ECP treatment with a concomitant decrease in mean cell volume, a decrease in mean corpuscular hemoglobin concentration, a decrease in serum iron, an increase in red blood cell distribution width, a decrease in ferritin, or an increase in total iron binding capacity.

In the analysis, 27 patients developed anemia, and 19 met the criteria for IDA. Patients developed IDA at a similar rate with both instruments, but 4 patients receiving ECP on CELLEX needed iron supplementation. The average hemoglobin decrease during therapy was 2.1 g/dL. Patients receiving ECP with the CELLEX instrument experienced a statistically significant larger drop in hemoglobin than those using UVAR (2.6 g/dL vs 1.3 g/dL; P =.02).

The authors found that the development and severity of IDA directly correlated to the frequency and total number of ECP treatments over time. Patients received ECP for anywhere from 2 weeks to 3.6 years, with an average of 10.2 months. ECP treatment ranged from 8 to 89 cumulative treatments, with an average of 32 treatments. Patients with anemia who received treatment twice weekly with either instrument experienced larger drops in hemoglobin compared with those on a less frequent schedule (2.6 g/dL vs 1.2 g/dL; P =.004). The drop in hemoglobin was greater among patients with IDA who received treatment twice weekly compared with patients with IDA who received less frequent treatment (3.4 g/dL vs 1.4 g/dL; P =.003).

Previous studies have suggested that IDA may develop because of retained blood products. The UVAR instrument has a manual return and may have about 150 mL of whole blood remaining in the equipment. The CELLEX is automated to complete the treatment by rinsing back the patient’s blood in a return line, which retains a few milliliters. The authors found that the CELLEX instrument led to patients developing IDA faster than the UVAR instrument.

“The introduction of a manual return as part of the ECP CELLEX procedure may be effective at decreasing blood loss by returning blood volume to the patient, though this protocol is not specifically required or suggested by the manufacturer,” the authors wrote.

Because of the risk of IDA in the majority of patients receiving ECP, the authors recommended that all patients be monitored for anemia.


Moosavi MM, Goodman AL, Duncan A, et al. Development of iron deficiency anemia in patients undergoing extracorporeal photopheresis: comparison of the UVAR and CELLEX instruments. J Clin Apher. Published online September 7, 2020. doi:10.1002/jca.21836