Extracorporeal Photopheresis Procedures Research Articles

Collection efficiency of mononuclear cells in offline extracorporeal photopheresis: can processing time be shortened?

Extracorporeal photopheresis (ECP) is a well-established but lengthy and burdensome cell-based therapy for various diseases such as cutaneous T-cell lymphoma, graft-versus-host disease and organ rejection after transplantation. The number of mononuclear cells (MNCs) that needs to be collected to obtain a clinical response to ECP is still under debate. The purpose of this retrospective study was to determine the number of lymphocytes, monocytes and neutrophils in mononuclear cell products (MCP) by flow cytometry and the collection efficiency in the offline ECP setting. We collected data from 10 different patients undergoing 162 ECP procedures using the Spectra Optia device for MNC collection. White blood cell (WBC) count of MCP was determined using a hematology analyzer. MNCs were analyzed for CD45 and CD14 expression by flow cytometry to exactly determine the collected lymphocyte and monocyte fractions. Collected MCP showed high cell yields with 55.3×106/kg MNCs and 41.1×106/kg lymphocytes. MCP were characterized by high MNC (81.3%) and low neutrophils (18.7%) percentage. Mean collection efficiency for WBCs and for MNCs was 23.9% and 62.0%, respectively. The MNC fraction showed a moderate to high correlation between peripheral blood cell count of patients and MCP count. This study is one of a few reports showing the monocyte-to-lymphocyte relation in MCP for ECP determined by flow cytometry. In comparison to historical data from inline ECP, the offline ECP processing one total blood volume results in considerably higher cell yields. For this reason, and to reduce the burden on patients, we propose that the offline ECP processing time can be substantially reduced.

Real-world evidence of heparin and citrate use in extracorporeal photopheresis: A hypothesis-generating data review of device settings and performance.

Extracorporeal photopheresis (ECP) is widely used for the treatment of cutaneous T-cell lymphoma, graft-vs-host disease, and other immune-related conditions. To avoid clotting during treatment, the ECP system used must be effectively primed with an anticoagulant. Heparin is the recommended anticoagulant for the THERAKOS CELLEX System, but acid citrate dextrose-A (ACDA) is often used. We compared system performance between these two anticoagulants for this ECP system. Deidentified data for ECP device performance were obtained at each treatment session, from automatically logged Smart Cards or labels completed by device operators. We compared the effects of ACDA or heparin on overall treatment duration, buffy coat (leukocyte) collection time, photoactivation time and the number of alarms and warnings. The variability in these parameters was also assessed. Data from 23 334 treat sessions were analyzed; ACDA was used in 34.4% and heparin in 65.6%. Overall, the ECP procedure duration, buffy coat collection time and photoactivation time were numerically similar regardless of whether ACDA or heparin was used, and regardless of needle mode. Photoactivation time variability was lower with ACDA compared with heparin in all needle modes. Among treatments that were completed automatically without any operator intervention, total treatment duration and photoactivation time were significantly reduced with ACDA use in both the double- and single-needle modes. The data presented indicate that, in both double- and single-needle modes, the THERAKOS® CELLEX® integrated ECP system performed similarly with ACDA compared to heparin, although ACDA demonstrated potential benefits in reducing variability in photoactivation time.

Real-World Experience in Extracorporeal Photopheresis for Adults with Graft-versus-Host Disease

Extracorporeal photopheresis (ECP) has shown efficacy in treating graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors. All consecutive adult patients with steroid-dependent or steroid-refractory GVHD undergoing off-line ECP were included in this single-center retrospective study. ECP was performed with a Spectra Optia device, processing 1 total blood volume, at a twice-weekly frequency for acute GVHD (aGVHD) and once weekly for chronic GVHD (cGVHD), and tapered individually according to clinical response. The cumulative incidence of response, including complete response (CR) and partial response (PR), were compared among patients grouped by different baseline, apheresis, and disease characteristics. Between January 2015 and May 2022, a total of 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of the ECP sessions. GVHD responded in 78% of patients (aGVHD: 57% CR and 4% PR; cGVHD, 39% CR and 48% PR). Overall survival was statistically greater for aGVHD patients who responded to ECP compared to those who did not respond (67.5% versus 26% at 1 year; P=0.037). Severity was an independent predictor of response in aGVHD, whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in cGVHD. Our findings support the effectiveness of this treatment schedule for GVHD. Further investigation is required to identify ECP-specific predictive factors, given that findings are not homogeneous across studies.

Effects of Extracorporeal Photopheresis on Quality of Life and the Course of Diseases in Patients With Mycosis Fungoides and Graft-Versus-Host Disease: A Single-Center Analysis.

The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in patients with Mycosis Fungoides (MF), as well as with Graft-versus-Host Disease (GvHD). LQ was monitored retrospectively by using the dermatology life quality index (DLQI) and Skindex-29 test before ECP onset and after the last ECP. Disease parameters were assessed by objective criteria i.e. number of associated medical drugs taken, intervals between therapeutic cycles, gradual change of the disease, and eventual side-effects and complications of ECP therapy. Fifty-one patients were treated with ECP during 2008-19; 19 out of 51 died, and follow-up was not completed in 13 patients. Finally, treatment protocols of 671 ECP procedures were evaluated in 19 patients (10 MF; 9 GvHD).MF and GvHD subpopulations did not differ in the individual scores of LQ questions, either before the outsetor after the last ECP. DLQI and Skindex-29 scores were ameliorated by the ECP therapy (p= 0.001 and p< 0.001, respectively) due to improvement of individual scores of feelings, daily/social activities (p< 0.05), and functionality (p≤ 0.05). The median interval between ECP cycles was extended from two to eight weeks (p= 0.001). Needs of GvHD patients for drugs being received for the underlying disease were reduced (p= 0.035). Two of the 10 MF patients worsened from stage IIA to IIIA. Severe or minor side effects leading to a therapy interruption were not recorded. Patients with GvHD experienced a notable decrease in the administration of drugs for their underlying condition, and there were no instances of severe side effects that resulted in the discontinuation of treatment. ECP is safe and effective for the treatment of MF and GvHD.

Extracorporeal Photopheresis Suppresses Transplant Fibrosis by Inducing Decorin Expression in Alveolar Macrophages.

Extracorporeal Photopheresis Suppresses Transplant Fibrosis by Inducing Decorin Expression in Alveolar Macrophages.

Extracorporeal photopheresis for the treatment of chronic graft versus host disease

ABSTRACT Objectives Chronic graft versus host disease (chronic GVHD) still remains the leading cause of late morbidity and mortality for allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. In this retrospective study, 53 consecutive allo-HSCT patients with chronic GVHD refractory to corticosteroids were treated with extracorporeal photopheresis (ECP). Methods This study was performed as a retrospective single-center study. Medical records of a total of 59 patients treated with ECP for chronic GVHD were reviewed. Results Best organ responses to ECP were observed in skin, mouth mucosa, eyes and liver. Overall response rate (ORR) to ECP was 81.2% (CR 17% and PR 64.2%). Overall survival (OS) was 84.9% and 36.7%, at 1 and 3 years, respectively. Female sex appears to have an advantage on ORR. Patients achieving ORR were able to maintain their responses with a prolonged continuation of treatments for +6 and +12 months indicating the benefits of longer ECP treatment. Discussion We found that patients with chronic GVHD who were treated with ECP for 12 months or longer had a higher response rate. Our findings in line with the data reported previously suggest that patients responding to ECP should continue longer therapy schedules to achieve a better and sustained response. In our cohort, long-term ECP therapy was safe and well-tolerated with no significant adverse effects. Best responses were observed in the patients with skin, eye, liver and oral involvement. The ECP procedure offers the advantage relative to the problems with typical immunosuppressive agents. The female sex appeared to have an advantage based on the cumulative probability of the OR after ECP for chronic GVHD.

MO1005: Analysis of Expression of Immune System Genes that are Responsible for Activation and Inhibition of T-Cell Immune Response in Renal Transplant Recipients after Extracorporeal Photochemotherapy

Abstract BACKGROUND AND AIMS Due to the increasing need for kidney transplantation, there is a demand for new methods of preventing rejection of the transplant based on the mechanisms of natural regulation of the immune response. Extracorporeal photopheresis (ECP) is one of these technologies whose clinical efficacy in the prevention and treatment of acute renal transplant rejection has been confirmed by many studies, but the mechanism of its effect has not been fully understood. Characterization of the genes responsible for the activation and inhibition of the immune response during ECP is an important step towards the modification of immunosuppressive therapy. The aim of this study was to analyze the changes in the expression level of the genes responsible for the activation and inhibition of the T-cell response in the recipients of the renal graft after ECP. METHOD An open cohort randomized trial was conducted with 20 patients who underwent a single group cadaver kidney transplantation from an unrelated donor. The recipients of the compared groups received standard immunosuppressive therapy and the same therapy in combination with ECP procedures, according to the study protocol. Each recipient of the main group received 15 sessions of ECP within 6 months. The level of gene expression was analyzed by real-time RT-PCR. Comparison of the study groups was carried out at point 1 (1st–4th day) and 2 (30th day). RESULTS The analysis of clinical data did not show statistically significant clinical differences, but in the specific consideration of each pair of cases, the tendency to some improvement in the transplant organ engraftment rate in the early terms after the transplant, and better survival of the graft and the recipient was revealed. For instance, patients of the main group revealed no transplant rejection by clinical laboratory signs as well as the results of histological examination of biopsy specimens. In the comparison group, acute graft rejection was clinically diagnosed and was confirmed by histological examination as humoral type rejection. The level of expression of genes involved in immune response regulation (CD28, CTLA4, PDL1 and FOXP3) and cytokine genes (TNFA, IL1, IL2, IL10 and IFNG) in the studied groups was determined. A decrease in the level of expression of the genes for the proinflammatory cytokines IL1, IL2 and IFNG was noted by the 30th day after transplantation. At the same time, the expression of the genes PDL1 and FOXP3, which regulate the development of the regulatory response, significantly increased by the 30th day after transplantation. Correlations of the level of gene expression with the presence/absence of rejection episodes have not been established. To assess the effect of the ECP on these gene expression, a comparison was made of the level sof transcript representation of patients receiving standard immunotherapy and immunotherapy in combination with ECP, and a significant increase in the expression of PDL1 and FOXP3 genes (Fig. 1A and B) was found in the group of patients who underwent ECP procedures (P = .0009 and .0013, respectively). CONCLUSION According to the results of comparative analysis, the level of expression of pro-inflammatory cytokines' genes IL1, IL2 and IFNG decreased to the 30th day after transplantation. A 30-day comparison between groups shows an increase in the expression level of the PDL1 and FOXP3 genes. Increased expression of these genes may be associated with the activation of regulatory T-cells and the development of peripheral tolerance and can become a criterion for the modification of immunosuppressive therapy.

Comparison of procedure times and collection efficiencies using integrated and multistep nonintegrated procedures for extracorporeal photopheresis.

BackgroundExtracorporeal photopheresis (ECP) is a blood‐based therapeutic procedure increasingly used for modulation of immune dysregulation in various underlying disease settings. The aim of this study was to compare the procedure times and blood collection efficiencies between the two approaches currently utilized in European centers: the integrated versus the multistep nonintegrated procedures.MethodsA retrospective data analysis was conducted, comparing treatment data from patients who received ECP therapy at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken GmbH, where the integrated and multistep nonintegrated procedures are routinely used in an approximated setup.ResultsDuring the observation period, a total of 15 patients who were treated with alternating systems on 2 consecutive days were identified. This allowed treatment pair comparisons with minimal interpatient variabilities, similar to a cross‐over design even though analyzed retrospectively. Total average procedure times with the integrated system were 99.3 vs 122.0 minutes with the multistep nonintegrated procedures, respectively. Significant differences were observed for all steps of the ECP procedure: (a) time for buffy coat collection, 66.5 vs 74.7; (b) handling/transfer, 2.8 vs 18.7; (c) irradiation, 20.3 vs 11.7; and (d) reinfusion/handling time, 9.6 vs 16.3 minutes. The calculated collection throughput was 7.79 mL/min for the integrated and 7.84 mL/min for the multistep nonintegrated procedures, and with a white blood cell (WBC) collection efficiency of 34.2% and 21.0%, respectively.ConclusionThe data presented in this study show a significant shorter overall procedure time and higher WBC collection efficiency for the integrated ECP system.

Impact of extracorporeal photopheresis on blood and coagulation parameters.

Extracorporeal photopheresis (ECP) is considered a safe treatment modality. We aimed to assess blood parameters including coagulation during ECP over time. We performed a long-term retrospective single-center chart review (laboratory parameters) of adult patients (n= 172) who had received ECP for any indication. We observed a significant decrease (p< 0.05) in erythrocytes, hemoglobin, and leukocytes compared to baseline levels after only one ECP procedure. This decrease persisted after 3-, 6-, 9-, and 12-months of ECP. A significant pathological decline of hemoglobin was observed in a higher proportion (26.4% and 25.2%, respectively) of patients after 6 (p= 0.0007) and 12 (p= 0.012) months of ECP. Mean corpuscular volume as well as hematocrit was significantly decreased at 3-, 6-, 9-, and 12-months of evaluation compared to baseline (p< 0.05). After 9 and 12 months of ECP we observed a further decline in lymphocyte counts (p< 0.05). Various coagulation parameters did not change significantly during ECP treatment. Even though not all alterations observed in peripheral blood of ECP patients in the present study were of clinical significance, risk for developing persistent anemia must be considered in patients undergoing ECP.

Extracorporeal photopheresis (ECP): in vitro assessment of procedure quality

Objectives: The purpose of this work was to validate the procedure of extracorporeal photopheresis (ECP) offline after the addition of 8- MOP and UV-A (PUVA) irradiation by carrying out functional tests as recommended by the GITMO/SIdEM guidelines. There is currently no general agreement on the protocol to be adopted for the biological validation of the ECP; in fact, it is required that the test needs to be reproducible, reliable and standardisable. So, the protocol needs to be replicated in every processing laboratory.Methods: in absence of guidelines and evidence to support ECP, we have chosen to monitor cellular apoptosis induced by 8-MPO and UV-A (PUVA) irradiation, after 1 h, 48 h, and 96 h, using double marking with FITC-Annexine V and 7-AAD and consequent cytofluorimetric evaluation.Results: the functional tests utilized reproduce in vitro the 8-MOP activation effects. Our data suggest that the use of double staining with FITC-Annexine V and 7-AAD and subsequent cytofluorimetric evaluation may represent a reliable and reproducible method for ECP biological validation.Conclusions: the work allowed us to review our ECP validation procedure. We will adopt as functional test the double marking FITC- Annex V and 7-AAD and reading in cytofluorimetry at +48h post PUVA. The test needs to be performed on each enlisted patient, during the first two procedures, with each modification of the set used and at each 8-MOP batch change. We do not know what is the impact of the ECP procedure in terms of clinical efficacy or if reinfused cells are biologically inactivated or not active in the patient with GvHD. Clinical follow-up must remain the key parameter for evaluating the response to ECP treatment because even qualified therapy becomes clinically irrelevant in a patient not responding to treatment.

The effect of cryopreservation on the parameters of mononuclear apoptosis during extracorporeal photopheresis

Introduction. The mechanism of action of extracorporeal photopheresis (ECP) is associated with the induction of apoptosis of lymphocytes, which cause the activation of antigen-presenting cells (APC). As a result of the use of ECF, the number of T-regulatory lymphocytes increases, which induces an immunosuppressive effect. The actual problem lies in the use of cryopreserved and photo-irradiated mononuclear cells.Aim — to analyze the functional features of cryopreserved mononuclear cells after ECP.Materials and methods. The study analyzed the indicators of early and late stages of apoptosis in the concentrate of mononuclear cells of different groups, depending on the time of collection and the type of exposure on these concentrates of mononuclear cells: immediately after apheresis (groups 1.1 and 1.2), and after ECP (groups 1.3, 2.1 and 2.2), groups 1.2 and 2.2 were after cryopreservation, and 1.3 — after cryopreservation, and then after ECP. 113 samples of mononuclear cell concentrates obtained from 12 patients with chronic graft-versus-host reaction (GVHD) were analyzed. All groups of samples were cultured to determine the dynamics of changes in indicators of early and late stages of apoptosis over time.Results. The proportion of lymphocytes in the late stage of apoptosis after 2 days cultivation, after the standard ECP procedure, was comparable to the proportion of lymphocytes in the late stage of apoptosis during ECP followed by cryopreservation of the leukoconcentrate.Conclusion. It is advisable to collect mononuclear cells, perform their extracorporeal photo-irradiation, and then divide the photo-irradiated mononuclear cells into several parts both for cryopreservation and for the return of non-cryopreserved photo-irradiated mononuclear cells to the patient.

Midline catheters for extracorporeal photopheresis in hematological patients.

Peripheral venous access for extracorporeal photopheresis (ECP) may be difficult in graft versus host disease (GVHD) patients, because of previous intravenous therapies and multiple peripheral cannulations; in this population of patients, ultrasound guided midline catheters may be an alternative option to central venous access. In this single-center, prospective preliminary study, we enrolled all consecutive patients with a diagnosis of GVHD and candidate to ECP, over a period of 10 months. We used inserted power injectable, non-valved, polyurethane, 20-25 cm single lumen midline catheters (MC). Sixty-nine ECP procedures were carried out in six patients, using single-lumen MCs for outflow (5Fr in 74% and 4Fr in 26% of cases). For inflow, we used 5Fr or 4Fr MCs, or central venous access devices previously placed for other clinical reasons. There were no catheter-related complications during the entire period of ECP treatment. Mean outflow was significantly higher for 5Fr than for 4Fr MCs (35.8 ± 7.3 vs 29.2 ± 7.8 ml/min; p = 0.0008) and the procedure time was significantly shorter (92.9 ± 9.2 vs 108 ± 13.2 min; p < 0.0001). In GVHD patients, ECP can be performed efficiently and safely using single lumen polyurethane power injectable MCs. The best results are obtained with 5Fr rather than with 4Fr catheters. This strategy of venous access should be implemented in DIVA patients requiring ECP treatments, and probably also in other types of apheresis.

Extracorporeal photopheresis chargemasters show haphazard billing practices.

United States healthcare spending continues to outpace other developed nations although efforts are being made to increase cost-transparency. Recent legislation requires hospitals to publish a chargemaster, a list of all billable procedure codes together with prices. Chargemaster prices have been shown to be highly variable, if available, and are not typically paid, but contribute to negotiated rates. Extracorporeal photopheresis (ECP) is performed for a limited number of indications and could serve as a marker of this variability. We investigated the availability of chargemaster documentation for ECP procedures and the variability of pricing as assessed by institutional characteristics. A list of centers with photopheresis systems was obtained from the device manufacturer and the institutional websites were analyzed for chargemaster list prices. Multivariate linear regressions were performed to compare impact of facility variables on chargemaster pricing. There are 139 locations in the US which are listed as referral centers for ECP; and chargemaster prices were available in 66.2% of these centers. The range was $571.48-183,452.00, maximum price 321 times greater than minimum, and the median price, after outlier exclusion, was $8989.06 (SD=$4361.72). ECP cost did not correlate with hospital size, facility type, ownership, number of hospitals in the referral region, hospital care intensity index, academic status, or region (p≥ .05). Chargemaster costs for ECP procedures are highly variable and nonuniform, and the current data available for patients undergoing these specialized apheresis procedures is insufficient to afford patients the ability to compare prices.

Program extracorporeal photophoresis in complex treatment of psoriatic arthritis

The results of complex treatment with the programmed procedures of extracorporeal photopheresis and methotrexate in patients with psoriatic arthritis for 12 months are presented. It has been established that program extracorporeal photopheresis in combination with basic therapy with methotrexate in patients with psoriatic arthritis have a significant effect on the relief of articular syndrome (reduction of morning stiffness, pain intensity, joint swelling). It was revealed that the inclusion of programmed extracorporeal photopheresis and methotrexate in the complex treatment of psoriatic arthritis reduces the level of circulating low molecular weight, medium molecular weight and high molecular weight immune complexes and in most cases leads to clinical and immunological remission. This is confirmed by a decrease in complaints of the severity of articular syndrome and a decrease in the clinical and laboratory activity of the disease (a significant decrease in the level of C-reactive protein, erythrocyte sedimentation rate). A scheme has been developed for the programmed use of extracorporeal photopheresis procedures in the complex treatment of psoriatic arthritis, which consists of 2 procedures every other day with an interval of 2,5-3 months for 12 months. Combined therapy with the programmed application of extracorporeal photopheresis procedures and methotrexate prolongs the period of disease remission and can be recommended for patients with psoriatic arthritis with high activity, insufficient effect of basic therapy and intolerance to higher doses of immunosuppressive drugs.

A simplified extracorporeal photopheresis procedure based on single high-dose ultraviolet A light irradiation shows similar in vitro efficacy.

Extracorporeal photopheresis (ECP) is one of the most widely used and effective cell-based therapies for the treatment of T-cell-mediated diseases. The patients' white blood cells (WBCs) are collected by apheresis and exposed to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light before retransfusion. The UVA/8-MOP combination has been in use in ECP for more than 4 decades; however, whether ECP can be simplified by UVA light irradiation only has never been analyzed. Peripheral blood mononuclear cells were treated with classical ECP or different UVA light doses only (UVAonly ). Treatment efficacy was investigated by apoptosis induction in WBC subsets, inhibition of T-cell proliferation, and the ability of monocytes to induce allogeneic T-cell expansion and to respond to lipopolysaccharide and interferon-γ stimulation in vitro. High-dose UVAonly treatment (5 J/cm2 ) was as efficient as ECP to induce apoptosis within 48 hours. UVAonly treatment modulated the composition of the surviving cells by improving monocyte survival and promoting CD8+ T-cell apoptosis. Both ECP and UVAonly treatment inhibited anti-CD3/anti-CD28 triggered T-cell proliferation. Interestingly, whereas ECP-treated monocytes exhibited a markedly reduced capacity to respond to stimulation and to induce allogeneic T-cell proliferation, UVAonly treatment preserved monocyte functionality to some degree. High-dose UVAonly and standard ECP showed comparable efficacy in inducing apoptosis and inhibiting direct T-cell proliferation. Hence, UVAonly treatment can be a simplified alternative to ECP therapy. Furthermore, increased monocyte survival with partially preserved functionality after UVAonly treatment may provide a novel method for immunoregulation.

Pilot study of a new online extracorporeal photopheresis system in patients with steroid refractory or dependent chronic graft vs host disease

BackgroundA new protocol has been developed on the Amicus Separator that enables the device to perform online extracorporeal photopheresis (ECP) procedures when used in conjunction with the Phelix photoactivation device and associated disposable kit. The objective of this study was to evaluate the safety and performance of the Amicus ECP System in adult subjects with steroid‐refractory or dependent chronic graft vs host disease (cGVHD).Study Design and MethodsEight subjects with mild to severe cGVHD underwent 31 procedures. Subject safety evaluations were performed pre and post procedure and adverse events (AEs) were recorded during treatment and 24 hours after the last procedure. In vitro evaluations of the treated cells included hematology counts and lymphocyte apoptosis, viability and proliferation as measures for ECP procedure validation.ResultsFor n = 23 evaluable procedures, median (range) procedure time was 88 (78‐110) minutes, during which 2.9 (0.6‐4.7) × 109 TNCs (approximately 90% MNCs) were treated and reinfused to the subjects. All subject safety evaluations (vitals, cell counts, plasma hemoglobin and bacterial and endotoxin testing) were within expected ranges. All device or procedure related AEs were mild in nature. After 24 hours in culture, 86 (52‐98)% of treated lymphocytes were apoptotic compared to 27 (15‐51)% in controls. Inhibition of lymphocyte proliferation was >91% in all procedures.ConclusionECP procedures were safely completed in adult subjects with SR‐cGVHD treated using the new online Amicus ECP system.

Extracorporeal photopheresis as first-line strategy in the treatment of acute graft-versus-host disease after hematopoietic stem cell transplantation: A single-center experience

Background aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD.

Bacterial contamination rates in extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is an immunosuppressive treatment that involves leukocyte apheresis, psoralen and UV light treatment, and subsequent reinfusion. Patients treated with ECP are usually immunosuppressed. Bacterial contamination therefore poses a much unwanted risk, but incidence data are lacking. We screened all 1922 consecutive ECP procedures scheduled within a roughly 3-year period for eligibility. Those with missing data on ECP method (inline or offline) or type of venous access (peripheral or central) were excluded. ECPs with complete aerobic and anaerobic microbial testing of baseline patient blood samples (n = 1637) and of ECP cell concentrates (n = 1814) were included in the analysis. A test for microbial contamination was positive for 1.82% of the cell concentrates, with central venous access was the most significant risk factor for the contamination (odds ratio = 19). Patient blood samples were positive in 3.85% of cases, but no patients became septic. Staphylococcus spp. were most abundant, and products with bacterial contamination did not cause side effects after reinfusion. There were no significant differences in contamination rates between inline and offline ECP. These findings stress the importance of sterile procedures and the benefits of using peripheral over central venous access for reducing the risk of bacterial contamination in ECP.

Retrospective Multicenter Study of Extracorporeal Photopheresis in Steroid-Refractory Acute and Chronic Graft-versus-Host Disease

Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory graft-versus-host disease (GVHD). This study's main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction. A retrospective observational series of 113 patients from 7 transplantation centers was analyzed. Sixty-five patients (58%) had acute GVHD (aGVHD), and 48 (42%) had chronic GVHD (cGVHD). All ECP procedures were performed with the off-line system. The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD. ECP was the second-line therapy in 48% of the aGVHD cases and in 50% of the cGVHD cases. 71% of the cases of aGVHD were grade III-IV, and 69% of the cases of cGVHD were severe. The overall response rate on day 28 was 53% (complete response [CR] rate, 45%) in the patients with aGVHD and 67% (CR, 23%) in those with cGVHD. Skin was the most frequently involved organ, with a response rate of 58% (CR, 49%) in the patients with aGVHD and 69% (CR 29%) in those with cGVHD. At the end of ECP treatment, 60% of patients treated for aGVHD who responded were able to stop steroid therapy, with a median dose reduction of 100%. Significant differences in overall survival were observed for patients responding to ECP with aGVHD (hazard ratio [HR], 4.3; P < .001) and with cGVHD (HR, 4.8; P=.003). Our data indicate that ECP is a valid therapeutic alternative in patients with steroid-refractory aGVHD and cGVHD, permitting significant steroid dosage reductions.

Automated mononuclear cell collection: a feasibility study employing a new software for extracorporeal photopheresis

Very recently, Fresenius Kabi, improved the software (autoMNC lymphocytes, SW 04.03.08) for mononuclear cells (MNCs) collection with the aim to ameliorate the quality of harvest, employing the automated autoMNC lymphocytes software SW 04.03.09. Herein, we report the results of an observational study evaluating the feasibility of MNCs collection in patients undergoing extracorporeal photopheresis (ECP) at our centre, using the new COM.TEC software 04.03.08c for MNC collection, afterwards integrated in the software 04.03.09, available on the market since November 2018. Thirty adult patients (21 males and 9 females) with GvHD, Chronic Lung Allograft Dysfunction or renal rejection, were consecutively enrolled to undergo 1 ECP procedure by the offline technique, according to our internal protocol, processing 1·5 blood volumes. Feasibility of collection was defined as: Hct in collection bag ≤5%, MNCs purity (percentage of MNCs/bag) ≥80%, MNCs collection efficiency (CE2) ≥60%, patient's platelet depletion ≤50%. Thirty ECP procedures were evaluated. Feasibility (defined by the four parameters previously described) of MNCs collection was observed in 1 out of the 30 harvests analysed. Median Hct in the product was 3·45% (IQR: 2·6-5·0), and median MNCs purity was 97·2% (IQR 89·1-98·6). Median CE2 for MNCs was 21·4% (IQR: 11·9-41·2), and median patient's platelet depletion was 36·2% (IQR 21·9-51·4). The autoMNC lymphocytes software SW 04.03.08c for MNCs collection in ECP setting demonstrated to collect a good quality product in terms of purity and RBC contamination even if the collection efficiency and platelet contamination must be improved.