Does Offline Beat Inline Treatment: Investigation into Extracorporeal Photopheresis

Abstract

Background: Extracorporeal photopheresis is a therapy based on the induction of apoptosis to cells harvested from peripheral blood, followed by direct retransfusion. Currently, there are two approaches: inline procedures, where cell harvesting, 8-methoxypsoralen (8-MOP) incubation, and UV irradiation is performed with a single device, and offline procedures, with collection in one device, followed by 8-MOP incubation/UV irradiation using a second device. Study Design and Methods: In a prospective crossover study, we compared an inline (Cellex, Therakos) with an established offline procedure (Optia, Terumo, and MacoGenic G2, Macopharma) in 6 patients, focusing on cell composition and apoptosis induction after 24 h. In total, 32 photopheresis treatments per device were performed. Results: We observed an overall 2-fold higher number of apoptotic “target” cells for each patient with offline treatment. All yields were stratified per patient. Yields were compared as ratio offline/inline for CD3+ (2.5-fold), CD4+ (2-fold), CD8+ (2.8-fold), CD56+ (2.8-fold), CD19+ (1.8-fold), CD15+ (0.5-fold), and CD14+ (2.2-fold) cells. Apoptosis induction was measured after 24 h with Annexin V/7-AAD for early and late apoptosis rates of CD3+ (CD4+, CD8+) and CD56+ cells. CD3+ cells of the inline treatment had an average of 88% (26% early, 62% late) of apoptotic cells compared to 75% (34% early, 41% late) in the offline treatment. Procedure duration ranged from 80 to 100 min inline, with a maximum of 1,500 mL processed blood, and 125–140 min offline, with at least 3,000 mL processed blood, depending on blood flow. Average hematocrit levels of the products were 2.7% inline versus 1.7% offline. Conclusions: The offline procedure, as established in our department, provides more apoptotic cells for treatment. The increased number of mononuclear cells collected outweighs a slightly reduced apoptosis rate after 24 h in comparison to the inline procedure. Besides this, the final decision for one or the other procedure has to take into account additional aspects, such as peripheral white blood cell count, hematocrit, and weight of the patient, required before apheresis, extracorporeal volume, and, last but not least, overall costs. The final criterion, however, has to be the reported clinical efficacy of the system applied.

Increasing the collection flow rate to 2 mL/min is effective and reduces the procedure time in off‐line photopheresis

“…ECP is used as an immunomodulatory form of therapy for various (auto)immune diseases and is generally very well tolerated. 1,9,[11][12][13] In the present study, no side effects appeared related to 22 patient treatments. A required minimum number of therapeutically effective cell counts (MNC) has been described, [6][7][8] however this is not the case for a maximum number of such cells.…”

Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs

“…The technique adopted to perform the procedure (inline or off-line) does not seem to influence the clinical response to the treatment. Nonetheless, some differences exist regarding the patient’s management and the product collected [ 32 , 33 ]. A paired trial compared mononuclear cell collection in two machines for the further inactivation through an inline or offline extracorporeal photopheresis procedure [ 34 ].…”

In situ off‐line extracorporeal photopheresis conducted in a real‐life situation at a Hemobiotherapy Department in France: A comparison of costs vs on‐line procedure

“…While on‐line procedure requires specific equipment and combines all the ECP steps in a single operation, and the off‐line requires two separate devices and handling of the collected leukocytes by a qualified healthcare professional between collection and irradiation of the sample. Both procedures seem associated with comparable performance (assessed by a number of mononuclear cells yield and lymphocytes proliferation inhibition test) and clinical results in the literature and per center experience 10,11 . Of note, lymphocytes proliferation inhibition tests are randomly carried out at the beginning of each month for each type of procedure and each first ECP procedure for each patient cared in the center.…”

“…Both procedures seem associated with comparable performance (assessed by a number of mononuclear cells yield and lymphocytes proliferation inhibition test) and clinical results in the literature and per center experience. 10,11 Of note, lymphocytes proliferation inhibition tests are randomly carried out at the beginning of each month for each type of procedure and each first ECP procedure for each patient cared in the center. Still, the online procedure is currently perceived as shorter and less expensive, even though the literature about these economic aspects remains limited.…”