UVAR XTS Research Articles

The CELLEX is comparable to the UVAR-XTS for the treatment of acute and chronic graft versus host disease (GVHD).

Two extracorporeal photopheresis (ECP) instruments, the CELLEX and the UVARXTS are currently being used "off-label" in the US for treatment of graft versus host disease (GVHD). Our study compared the performance of the two instruments in the setting of acute and chronic GVHD. We retrospectively analyzed the outcomes of patients with steroid refractory or steroid resistant GVHD undergoing ECP at Barnes Jewish Hospital. Multivariate logistic regression was used to evaluate the comparative efficacy of the two instruments with respect to steroid dose reduction (≥50% from baseline) and clinical improvement in GVHD. Chi-square/Fisher exact tests were used to compare the incidence of adverse events, while multivariate Cox regression was employed to assess a potential difference in mortality between the two instrument treatment cohorts. After adjusting for potential confounders, there was no significant difference in the odds of steroid dose reduction (OR = 1.41, 95% confidence interval [CI]: 0.51-3.90, p = 0.50) or clinical improvement (OR 2.0, 95% CI: 0.63-6.41, p = 0.24) between the two instrument treatment cohorts. The frequency of adverse events (CELLEX 45.4%; UVAR XTS 40.5%, p = 0.55) was also comparable between the cohorts. There was no significant difference in mortality of either acute or chronic GVHD patients when treated by the CELLEX as compared to the UVAR-XTS (aHR 0.66, 95% CI: 0.35-1.25, p = 0.20). The efficacy and safety of the two ECP instruments, the CELLEX and the UVAR-XTS, are comparable for the treatment of acute and chronic GVHD.

Iron Deficiency Anemia in Patients Undergoing Extracorporeal Photopheresis for Cutaneous T-Cell Lymphoma.

To describe the indicidence and severity of iron deficiency anemia (IDA) in patients who have received extracorporeal photopheresis (ECP) treatment of cutaneous T-cell lymphoma (CTCL). We performed a retrospective study during a 9-year period of patients with CTCL who were treated with ECP. ECP was performed with UVAR XTS and CELLEX (Therakos Inc). IDA was defined by a drop in hemoglobin (Hb), mean cell volume (MCV), and increased red blood cell distribution width (RDW). We identified a total of 36 patients; 1 patient was excluded due to severe anemia. In 35 patients, initial hemoglobin values ranged from 9.8 g per dL to 15.9 g per dL, and patients received 4 to 327 ECP treatments. In all, 28 patients showed decreases in Hb of 0.8 g per dL to 6 g per dL during treatments. Chronic ECP led to IDA in 28 of 35 patients with CTCL. IDA occurs due to blood loss when ECP equipment does not return full blood volume to patients.

Extracorporeal photopheresis for graft versus host disease: Identifying a clinical pathway and associated resource utilization.

Extracorporeal photopheresis (ECP) is an established therapy for the treatment of graft-versus-host-disease (GVHD) following an allogeneic stem cell transplant. We performed a prospective analysis of patients receiving ECP treatment for GVHD to identify a clinical pathway and resource utilization of this process. The cohort included consecutive allogeneic stem cell recipients with GVHD. ECP was performed using the CELLEX Photopheresis System or the UVAR XTS Photopheresis System (Therakos, Inc, Exton, PA). A clinical pathway was developed and a time and motion study was conducted to define the resource utilization and costs associated with ECP. Patients were treated with either CELLEX (n = 18 procedures) or UVAR (n = 4 procedures). Total time commitment for each procedure for the 2 machines differed. The time for ECP was 117 min (median, range: 91-164 min) using CELLEX and 161 min (median; range: 140-210) using the UVAR-XTS machine. Total costs of each ECP procedure were $3420.50. There is a considerable time commitment of the patient and the clinical staff when employing ECP to treat GVHD. ECP costs are significant considering this is a prolonged therapy continued for several months. With this finalized pathway and costs, we have a standardized clinical pathway for the treatment of GVHD. We are addressing minimizing resource utilization while emphasizing quality care for these patients.

Safety and collection efficiency with a lower transfusion threshold for extracorporeal photopheresis in adult patients with graft-versus-host disease.

Extracorporeal photopheresis (ECP) is an established treatment for graft-versus-host disease (GVHD). Various haematocrit thresholds have been used to trigger red blood cells transfusion prior to ECP. Moderate-to-severe GVHD is frequently complicated by anaemia; the safety and collection efficiency with a lower haematocrit for ECP is unknown. We prospectively enrolled 26 consecutive adult GVHD patients with haematocrits between 25% and 28·9% who received ECP on the CELLEX system. Preprocedural transfusion was withheld. We monitored the adverse events and transfusions avoided. A complete blood cell count with differential was performed on preprocedural peripheral blood and buffy coat collected. Lymphocyte fold enrichment (LFE) was compared between this cohort and two historical control groups with haematocrits of 29% or higher. Red Blood Cells transfusion was avoided in the lower-haematocrit cohort without adverse events. The median LFE was 4·5 (95%CI, 3·1-5·7) in the lower-haematocrit cohort and 5·2 (95%CI, 4·1-6·5) in the higher-haematocrit CELLEX-treated control group. The median difference was 0·7 (95%CI, -0·3 to 2·0, P = 0·14). It could not be established that the lower-haematocrit cohort was non-inferior to the higher-haematocrit control group with a prespecified non-inferiority margin of 1·3. However, LFE was significantly higher in the lower-haematocrit cohort than the higher-haematocrit UVAR XTS-treated control group (P < 0·01). Buffy coat can be collected for ECP using CELLEX in GVHD patients with a haematocrit of 25% or higher, with a collection efficiency superior to that in patients with higher haematocrits but treated using UVAR XTS. No increase in adverse events was observed at these lower haematocrits.

The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society.

SummaryExtracorporeal photopheresis (ECP) has been used for over 35 years in the treatment of erythrodermic cutaneous T‐cell lymphoma (CTCL) and over 20 years for chronic and acute graft‐versus‐host disease (GvHD) and solid organ transplant rejection. ECP for CTCL and GvHD is available at specialised centres across the UK. The lack of prospective randomised trials in ECP led to the development of UK Consensus Statements for patient selection, treatment schedules, monitoring protocols and patient assessment criteria for ECP. The recent literature has been reviewed and considered when writing this update. Most notably, the national transition from the UVAR XTS ® machine to the new CELLEX machine for ECP with dual access and a shorter treatment time has led to relevant changes in these schedules. This consensus statement updates the previous statement from 2007 on the treatment of CTCL and GvHD with ECP using evidence based medicine and best medical practise and includes guidelines for both children and adults.

Linear relationship between lymphocyte counts in peripheral blood and buffy coat collected during extracorporeal photopheresis

Extracorporeal photopheresis (ECP) is commonly used to treat patients with graft-versus-host disease (GVHD) and lung transplant rejection (LTR) in our institution. The quantitative relationship between the number of white blood cells treated during ECP and the cell count in peripheral blood is unclear. Patients with GVHD and LTR receiving ECP with either UVAR XTS or CELLEX (Therakos) were prospectively recruited for this study. A complete cell count with differential was performed on preprocedural peripheral blood and samples from the collected buffy coats. Correlation analysis and linear regression were performed between cell counts in peripheral blood and buffy coat. Collection efficiency was compared between UVAR XTS and CELLEX. In all 52 patients, lymphocyte counts in buffy coat and peripheral blood showed strong correlation (r values were 0.85 and 0.983 for UVAR XTS and CELLEX, respectively; p < 0.001) with slopes of 2 and 5.1 for UVAR XTS and CELLEX, respectively (p < 0.001). The quantitative relationship remained robust in patients stratified by diagnoses. Monocytes also showed consistent correlation and linearity, but not neutrophils or combined white blood cells, red blood cells, or platelets. CELLEX enriched approximately twice as many lymphocytes and monocytes than UVAR XTS per procedure (p < 0.001). The preprocedural peripheral lymphocyte count can predict the number of lymphocytes within the buffy coat collected during ECP, which may justify the use of peripheral lymphocyte count as a surrogate for the cell dose treated per procedure. Peripheral monocyte counts may serve as an alternative. CELLEX is more efficient in collecting lymphocytes and monocytes than UVAR XTS under conditions tested.

Linear Relationship Between Lymphocyte Counts in Peripheral Blood and Buffy Coat During Extracorporeal Photopheresis in Patients with Graft-Versus-Host Disease

AbstractAbstract 4171 BackgroundExtracorporeal photopheresis (ECP) is a treatment modality that entails leukapheresis followed by mixing the buffy coat with methoxsalen (8MOP) and exposing it to UVA light. The buffy coat is then returned to the patient. The treatment is thought to have an immunomodulatory effect and is most commonly used to treat cutaneous T cell lymphoma, acute and chronic graft-versus-host disease (GVHD), and heart and lung allograft rejection. The exact mechanism and optimal dose of cells to be treated is unknown. The primary goal of this study is to examine the quantitative relationship between cell counts in peripheral blood (PBL) and buffy coat collected during ECP. Once this relationship is understood, the PBL cell count may serve as a surrogate marker for cell dose treated and help predicting the efficacy of ECP. The secondary goal of the study is to compare the cell collection efficiency of the two instruments currently used for ECP in the United States, UVAR XTS and CELLEX (Therakos, Exton, PA). MethodsTwenty six patients with GVHD were prospectively recruited for this study which was approved by the institutional review board. ECP was performed with either UVAR XTS (5 cycles with small bowl) or CELLEX (1500 mL of whole blood processed). PBL was drawn within 24 hours prior to the procedure for complete cell count with automated differentials (CBC). At the end of cell collection but prior to 8MOP treatment, 1 mL of buffy coat was drawn from well-mixed treatment bag for CBC. Spearman correlation analysis was performed between cell counts in PBL and buffy coat, including leukocyte counts (WBC), differential counts (neutrophil, lymphocyte and monocyte), and red cell counts (RBC). Collection efficiency was assessed in two ways: (1) the ratio of lymphocyte count in buffy coat to that in PBL (fold enrichment), and (2) the percentage of total lymphocytes collected [(lymphocyte count in buffy coat × treatment volume × 100)/(lymphocyte count in PBL × total blood volume estimated based on height and weight)]. These two variables were compared between UVAR XTS and CELLEX by Mann Whitney test. A double-sided p value was set at 0.05. Data visualization and statistical analysis were performed using GraphPad Prism 5 and IBM SPSS 19. ResultsA total of 22 patients were included in the final analysis after excluding 4 patients due to incorrect sampling of buffy coat. Seven patients were treated with UVAR XTS and 15 patients with CELLEX. The demographics (gender, race, age, weight, height, and estimated total blood volume), peripheral WBCs, Hemoglobin and hematocrits were not significantly different between the two groups.Lymphocyte counts in PBL significantly correlated with those in buffy coat collected by UVAR XTS (r=0.79, p<0.05) and CELLEX (r=0.92, p<0.0001). Linear relationships were observed with a slope of 1.7 (95% CI, 1.3–2.2) for UVAR XTS and a slope of 5.1 (95% CI, 4.7–5.4) for CELLEX (Figure 1A). Monocyte counts in PBL and buffy coat collected by UVAR XTS (r=0.82, p<0.05) and CELLEX (r=0.84, p<0.0001) also had robust correlations. There were no significant correlations for RBCs or neutrophil counts between PBL and buffy coat collected by either instrument. For the overall WBCs, there was only a weak but significant correlation for CELLEX (r=0.53, p<0.05).UVAR XTS enriched the lymphocyte counts by 2.2 ± 0.4 folds in buffy coat compared to PBL during ECP while CELLEX enriched the lymphocyte counts by 5.3 ± 0.4 folds (Mean ± SE, p<0.001, Figure 1B). UVAR XTS collected 9.9 ± 5.2% of total lymphocytes during each treatment while CELLEX collected 19.8 ± 8.6% of total lymphocytes (Mean ± SE, p<0.005, Figure 1C). ConclusionThere is a robust linear relationship between PBL and buffy coat lymphocyte counts, which may allow PBL lymphocyte count to be used in future studies as a surrogate for number of cells treated. This relationship also ensures a practical way to correlate cell dose with outcome. CELLEX is significantly more efficient in collecting lymphocytes than UVAR XTS. Approximately twice as many lymphocytes are treated with CELLEX than with UVAR XTS during each procedure. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Extracorporeal Photopheresis (ECP) in Kidney Allograft Recipients: 1-Year Followup

Background: ECP is considered a promising immunomodulatory therapy used for treatment of acute allograft rejection in solid organ transplant patients (pts) and GVHD. We report on early results of cadaver KTx in 20 paired recipients, all of them on standard immunosuppression (MPA+CNI+prednisone), and 10 of them additionally treated with 12-16 ECP procedures in the first 3 months (M) following KTx. Methods: There was no significant differences between controls and ECP group in term of age (47 11 vs 43,4 13y), gender of pts (3 vs 4 F), cause of end stage kidney disease, cold ischemia time, diabetes, hypertension, CsA/TAC concentrations, MPA dose, BMI (24,8 2 vs 26,2 5), mean HLA mismatch (2,6 vs 2,75) and sensitization. ECP procedures were conducted using UVAR XTS (Therakos, Exton, PA), an automated system for leukocyte separation and photoactivation (with injection of Methoxsalen). All pts were followed by means of eGFR and peripheral WBCs, T-cell,B,NK, Treg, DCs counts and phenotype. Results: In ECP group a positive tendency to higher GFR at M 6 (67,5 ±10 vs 53,6± 3; p=0.03) and M 12 (64,4 ±8 vs 59,5± 3; p=0.09 in Wilcoxon test) was observed. Transplant related complications are summarized in table1. All rejections (all cellular) were successfully treated with steroid pulse in both groups. One recipient from ECP group who experienced rejection have had unstable CNI levels in the first 6 months and might not response to ECP due to permanent low number of WBCs.Table: [Transplant related complications]Conclusions: An addition of ECP to standard immunosuppression in the first post-KTx year was associated with favorable kidney allograft function and less opportunistic infections. Acute rejections in ECP treated recipients appeared after 6 M and were reversible.

Application of Extracorporeal Photopheresis in Kidney Transplant Recipients: Technical Considerations and Procedure Tolerance

Background Extracorporeal photopheresis (ECP) is considered to be a promising immunomodulatory therapy in diseases caused by aberrant T lymphocytes. ECP has been used in patients with graft-versus-host disease and systemic scleroderma as well as in solid organ rejection. Herein we report our experience with 148 ECP procedures performed in 10 kidney transplant recipients (12–19 sessions per patient). In 2 subjects, ECP was introduced because of a steroid-resistant rejection episode, and in 8 as supportive treatment in addition to standard immunosuppression in the first 3 months after transplantation. ECP procedures were performed using the UVAR XTS device (Therakos, Exton, PA), an automated closed system for white blood cell separation and photoactivation (ultraviolet light A) with methoxsalen. Results Vascular access was arteriovenous fistula (n = 99), permanent catheter (n = 16), peripheral vein (n = 25), or polytetrafluoroethylene graft (n = 8). Mean blood flow rate was 35.5 ± 5 mL/min. Single ECP procedures lasted 175.5 ± 35 min (range, 120–277), including photoactivation (33.3 ± 30 min). Treatment volume (buffy coat) was 228.4 ± 34 mL per session. Total fluids administered per session were 449.5 ± 60 mL, and mean heparin dose was 5,979 ± 530 IU. ECP-related side effects were transient hypotonia (n = 2), increased body temperature (up to 37.5°C; n = 4) and red blood cell loss due to a clotted kit or a technical problem with reinfusion (∼100 mL; n = 3). Conclusions Vascular access for ECP was established in all transplant recipients, using even peripheral veins. Side effects associated with ECP were fairly tolerable by kidney allograft recipients. Caution must be paid to patients with fluid restriction (∼450 mL saline infusion) or the risk of bleeding due to anticoagulation.

Multicenter Photopheresis Intervention Trial in Early-Stage Mycosis Fungoides

To demonstrate the efficacy of the UVAR XTS Photopheresis System and evaluate health-related quality of life in patients with early-stage mycosis fungoides (MF). Extracorporeal photopheresis was administered 2 days every 4 weeks for 6 months. Patients with partial responses by skin weighted assessment continued for 6 months; nonresponders added oral bexarotene and/or interferon α. Health-related quality of life was assessed at baseline and every 3 months with 3 validated tools. Nineteen patients with early-stage MF (7 men, 12 women; 16 white, 3 African Americans) with median age of 63.5 years (range, 46-85 years) participated. Their stages were IA (n = 3), IB (n = 14), and IIA (n = 2). The overall response rate for extracorporeal photopheresis (ECP) alone, was 42% (8/19; including 7 partial response, 1 complete response), with a median of 12 ECP sessions (range, 3-32) given over a median of 12 months (3-32 months) and with an overall duration of response of 6.5 months (range, 1-48 months). Seven patients with stable disease at 3 months received additional bexarotene (3/5; 1 complete response) or bexarotene plus interferon α (1/2), and 4 (57%) of 7 responded. Treatment-related adverse effects were limited to those expected with interferon (fatigue, nausea, vomiting, and diarrhea), or with hypertriglyceridemia and bexarotene. Trends in health-related quality of life indicated an improvement in emotional scores over time. ECP is effective for patients with early-stage MF alone or in combination with biologic response modifiers with low toxicity and improved quality of life.

The use of fluid boluses to safely perform extracorporeal photopheresis (ECP) in low‐weight children: A novel procedure

Apheresis procedures in small children are technically challenging and require special planning with attention to extracorporeal volume. Discontinuous procedures such as extracorporeal photopheresis (ECP) require additional consideration. Alternative methods to perform ECP have been utilized in small children that require manipulation of mononuclear cells outside the standard closed-loop system. We present a safe and feasible alternative to the procedure for children who weigh less than 40 Kg, while maintaining a closed loop, sterile system utilizing the UVAR XTS device. A retrospective chart review was performed analyzing the use of fluid boluses (normal saline in those between 20 and 40 Kg, 5% albumin in those under 20 Kg) before ECP. Eleven patients underwent 334 ECP procedures for acute and chronic graft-versus-host disease (n = 9), and for prevention of graft-versus-host disease (n = 2). Volumes of fluid boluses were calculated based on the expected extracorporeal volume during the first draw cycle. Treatments consisted of at least three draw cycles using the 125 mL bowl. The median weight was 28.5 Kg (range 19 to 39); nine of 11 required red cell transfusions to maintain adequate hematocrit. Complications attributed to ECP included tachycardia, dizziness, nausea, and hypotension; these occurred either in combination or isolation in 31% of the procedures and resolved following additional fluid boluses. Only three (0.8%) required early photoactivation due to these complications. The median time to completion of treatment was 2 h and 58 min (range 1:30 to 5:03). ECP is well tolerated in low-weight pediatric patients if hematocrit and hydration are carefully maintained.

Photopheresis in pediatric patients with low‐body weight using the UVAR® XTS™ system

Photopheresis (ECP) with the UVAR XTS system has been limited to patients with a body weight > 40 kg, because extracorporeal blood volumes (ECV) may exceed 15% of the total blood volumes in low-body-weight patients. Because of these instrument characteristics, the use of ECP is limited in pediatric patients. In 5 patients (age 4 to 15 years) with graft-versus-host disease and with a body weight between 13 and 34 kilograms, photopheresis was performed using the UVAR XTS system. In 3 patients ECP could be performed by balancing the ECV with saline infusions. In 2 patients the system was modified in that the instrument was primed with packed red cells. During the treatment, fluid balance was guaranteed by a reservoir from a transfusion bag connected in parallel. Together 223 procedures were performed, among them 28 with the modification of the system. The treatments were well tolerated, and no episodes of hypotension were observed. It is possible to run ECP in low-body weight patients with the UVAR XTS system.

Safety of a new, single, integrated, closed photopheresis system in patients with cutaneous T-cell lymphoma

Extracorporeal photopheresis (ECP) is an approved palliative treatment for cutaneous T-cell lymphoma (CTCL). The THERAKOS CELLEX (continuous flow separation) system (Therakos, Exton, PA, U.S.A.) has been developed from the current THERAKOS UVAR XTS system. It is designed to reduce treatment times and extracorporeal volumes, and allows the use of either a single- or a dual-needle configuration. To assess the safety of the THERAKOS CELLEX system to provide ECP for patients with CTCL. Patients received ECP with the THERAKOS CELLEX system for up to 6 months. The treatment schedule was defined by their current treatment and response to ECP. At least 150 treatments were required to assess safety of the new system. Safety was assessed using reports of adverse device effects (ADEs) and unanticipated ADEs (UADEs), device malfunctions and defects, vital signs, laboratory parameters and physical examinations. Thirteen patients were enrolled and 12 completed the study; 155 ECP treatments were initiated and 153 completed. There were no ADEs or UADEs reported during the study. The mean treatment time was shorter for patients who received dual- compared with single-needle treatments (74.4 vs. 103.0 min, P < 0.0001) and the extracorporeal volume was lower (216 vs. 266 mL). This new ECP system provides lower extracorporeal volumes, faster treatment times, and flexibility to use either single- or dual-needle access, while not being associated in this study with any ADEs, and therefore having a positive benefit-risk ratio for patients with CTCL.

Exclusive use of acid citrate dextrose for anticoagulation during extracorporeal photopheresis in patients with contraindications to heparin: An effective protocol

Extracorporeal photopheresis (ECP) routinely uses heparin for anticoagulation. For patients with contraindications to heparin, alternative anticoagulation using acid citrate dextrose (ACD-A) has been reported to be safe and effective. However, detailed ECP protocols that exclusively use ACD-A anticoagulation and minimize citrate toxicity have not yet been published. We report a protocol that completely replaces heparin with ACD-A for ECP, which was developed at the University of California, Los Angeles (UCLA), and our experience since its implementation. ECP was performed with the UVAR XTS photopheresis system using ACD-A and control of the rate of citrate infusion. Calcium gluconate solution was administered prophylactically and as needed for symptoms of citrate toxicity. The medical records of patients who underwent ECP using the ACD-A protocol between January 2003 and July 2006 were reviewed. The incidence and severity of citrate toxicity and the technical data for all procedures were analyzed. During this period, 94 ECP procedures were performed with ACD-A anticoagulation on five patients. All patients tolerated the procedures well without significant complications. Only minimal symptoms of citrate toxicity (grade 1) were observed in 24.5% of all procedures; symptoms resolved promptly following administration of additional calcium gluconate. In conclusion, an effective protocol for ECP using ACD-A anticoagulation exclusively in patients with contraindications to heparin employs continuous monitoring of flow rates and prophylactic administration of calcium gluconate to minimize citrate toxicity.

Extracorporeal photopheresis improves nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: Three case reports and review of literature

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a recently recognized systemic fibrosing disorder that develops in the context of renal insufficiency. Its predominant manifestation is severe cutaneous fibrosis, often causing disabling contractures of neighboring joints. No therapy is consistently effective, and etiology and pathogenesis remain obscure. However, gadolinium-containing contrast agents used in magnetic resonance imaging or angiography have recently been strongly linked to the development of fibrosis in NSF. We report a clinical response to treatment with extracorporeal photopheresis (ECP) using the Therakos UVAR XTS system in three cases of NFD/NSF associated with flexion contractures affecting all four limbs. All three patients were receiving renal replacement therapy for longstanding end-stage renal failure. All three showed clinical response with softening of skin plaques at the end of four cycles, and improved range of movement in all four limbs on completion of treatment. The first patient, with NFD/NSF of 4.5 year's duration, was able to resume most activities of daily living although still chairbound, while a second patient with more recent onset of NSF was able to walk short distances with the help of Zimmer frames by the end of 16-18 cycles of treatment, having been chairbound pretreatment. A third patient with milder initial symptoms also experienced significant improvement after a shorter course of ECP treatment. Our experience with these three patients confirms previous case reports, suggesting that ECP may be effective in NFD/NSF.

Changes in L-Selectin Expression by T Lymphocytes after Extracorporeal Photochemotherapy.

Extracorporeal photochemotherapy (ECP) is an emerging treatment modality for steroid-refractory acute and chronic graft versus host disease (GVHD). The mechanisms by which ECP works are still not fully understood, and modulation of dendritic cell subpopulations, a shift of cytokine profile from Th1 to Th2 and an increase of T-cell regulatory (Treg) cells have been related to the ECP beneficial effect. Changes on T-lymphocyte subsets other than Treg have been reported after ECP (Biol Blood Marrow Transplant 2006; 12(1 Suppl 2):22–30.). We analyzed the effect of ECP on the T lymphocyte subsets of sixteen children receiving this form of therapy. Steroid refractory GVHD was defined as failure to respond to 2 mg/Kg/day of methylprednisolone after 5 days (acute GVHD) or failure to respond to steroids or flare of disease activity upon tapering (chronic GVHD). ECP was performed by an alternative approach to that of the classical UVAR XTS system. This alternative method is based on a continuous-flow cell separator (COBE Spectra) that allow to process more mononuclear cells in a smaller volume and it is less time-consuming, both important advantages for pediatric patients. We studied the L-selectin (CD62L) and the CD45RA expression on CD4 and CD8 lymphocytes by flow cytometry. This combination allowed us to distinguish naive (TN, CD62L+CD45RA+), central memory (TCM, CD62L+CD45RA+), effector memory (TEM, CD62L+CD45RA+), and terminal differentiated T cells (TT, CD62L+CD45RA+), as described in Science 2000; 290:92–97. We compared the proportion of each of these four subpopulations, as well as the L-selectin positive and L-selectin negative ones, in samples collected from peripheral blood before the first (PRE) and after the last (POST) ECP procedures. Statistical analyses were done by the Wilcoxon signed-rank test. Results are shown in the following tables:CD4 SUBSETS & ECPPREPOSTp valueTN6.58 ± 2.396.18 ± 2.960.2003TCM58.17 ± 4.4943.85 ± 4.780.0268TEM34.64 ± 4.5146.86 ± 4.890.0356TT0.6 ± 0.183.11 ± 1.460.1704CD62Lpos64.76 ± 4.450.03 ± 5.450.0268CD62Lneg35.23 ± 4.449.97 ± 5.450.0268CD8 SUBSETS & ECPPREPOSTp valueTN16.95 ± 3.9412.53 ± 4.050.2343TCM28.8 ± 4.9512.27 ± 2.860.0013TEM46.62 ± 5.7951.4 ± 4.220.1477TT11.17 ± 3.3423.52 ± 4.790.0105CD62Lpos45.75 ± 6.124.8 ± 5.340.0174CD62Lneg53.8 ± 6.0774.92 ± 5.310.0174The clinical outcome of the patients was always positive, with more than 50% achieving complete remission. The proportion of L-selectin expressing T lymphocytes significantly diminished after ECP, both in CD4 and in CD8 cells. The reason for these changes are currently unknown. L-selectin is an important T-cell homing receptor for T-cell entry into lymph nodes via high endothelial venules. Expression of CD62L is rapidly lost following T-cell receptor activation, leading to exit from the lymph node into the periphery and sites of inflammation. CD62Lneg and CD62Lpos also differ in their functional abilities, such as cytokine secretion and cytolytic potential. Our results suggest that ECP may have an impact in the trafficking patterns of T lymphocytes, redirectioning T cells from lymphoid to extralymphoid organs. In addition, ECP was associated to a redistribution of the pool of non-naive T lymphocytes.

Extracorporeal Photopheresis as a Treatment for Patients with Severe, Refractory Atopic Dermatitis

Introduction: Atopic dermatitis (AD) is a complex disease with a variety of possible treatment regimens. The study objective was to demonstrate that methoxsalen used in conjunction with the Uvar XTS photopheresis system (Therakos, Exton, Pa., USA) is safe and can have a clinical effect on the skin manifestations and the quality of life in patients with severe, refractory AD. Methods: Single-arm, open-label treatment using the Uvar XTS photopheresis system. Seven patients (4 male and 3 female, median age: 47 years) with severe (SCORAD >45) AD of at least 12 months duration who in the preceding 12 months had been refractory to all 3 of the first-line therapies for AD, i.e. topical steroids, topical calcineurin inhibitors and one form of phototherapy (UVA, UVB or PUVA), or to one of the second-line therapies like systemic steroids or cyclosporine were included in the study. Treatment consisted of two extracorporeal photopheresis treatments (ExP) on successive days every 2 weeks for a minimum of 12 weeks to a maximum of 20 weeks. Quality of life assessment was performed with the SF-36 Health Survey and the Functional Assessment of Chronic Illness Therapy FACT-G Survey. Clinical improvement was documented with SCORAD assessment. Results: ExP led to a significant decrease in the SCORAD score from 77.7 after 10 cycles to 55.6. Patients reported that they had begun to notice improvement of their skin conditions after 5 cycles of photopheresis. The FACT-G score showed significant improvement from 64.8 to 72.9 (p < 0.05) and the SF-36 Health Survey showed significant improvement in the emotional well-being subscores (p < 0.05). Conclusions: ExP can have a significant therapeutic effect on the skin and quality of life improvement in a selected group of patients with severe AD who are refractory to conventional forms of therapy. However, larger studies are needed to further evaluate its therapeutic potential.

Intensive extracorporeal photochemotherapy in pediatric patients with chronic graft‐versus‐host disease (cGVHD)

Extracorporeal photochemotherapy (ECP) is an alternative treatment approach in the management of chronic graft-versus-host disease (cGVHD). However, few reports have investigated the optimal treatment schedule of ECP. We treated seven pediatric patients with steroid-resistant or -dependent cGVHD with ECP. Using the Therakos UVAR XTS system, ECP was begun three (three patients) or five (four patients) times a week initially. Complete and partial responses were obtained in three patients. Three of seven patients died of GVHD-related complications. In this group initial intensive ECP did not improve the rate of response. However, this schedule appeared well tolerated.

Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease

Background: Chronic graft-versus-host disease (cGVHD) can arise frequently as a late complication after allogeneic hematopoietic cell transplantation. Patients with extensive disease to date require intensive and long-term immuno-suppression. We aimed to share our single center experience using extracorporeal photoimmunotherapy (ECP) in our steroid refractory extensive cGVHD patients. Patients and Methods: Eight patients with a median age 42 (range, 17–43) and M/F: 2/6 were treated with ECP (UVAR XTS) on 2 consecutive days every 2–4 weeks until resolution of GVHD over a period of 6–15 months concomitantly with immunosuppressive agents. Beyond extensive steroid refractory cutaneous cGVHD, three patients had also bronchiolitis obliterans (BO). Skin scores were assessed by an experienced dermatologist. Clinical, laboratory and radiological findings after 4 months of ECP were accepted as response criteria. The patients received in this almost fully automated system mean 261.4 ml buffy-coat was processed within 193 min using UVADEX sterile solution. Results: After a median of 12 cycles of treatment, 6 patients showed a favorable response. ECP was tolerated well only one patient developed Gr4 thrombocytopenia and another patient had a massive GIS bleeding due to an esophageal tear. Reduction in cholestatic parameters was observed in patients with liver cGVHD, improvement in respiratory functions and CT evaluations in two, and reduction in immunosuppressive requirement in all patients. The most impressive result was the reduced need for hospitalization of these patients and improvement of skin lesions. All but one of the skin biopsy scores was also better after ECP. Conclusion: As extensive cGVHD is a life devastating disorder, every attempt to improve the quality of life should be evaluated carefully. Our findings suggest that ECP is a safe and effective adjunctive therapy for steroid refractory extensive cGVHD of the skin. ECP will find a place both for the treatment and may be for the prevention of GVHD as well.

Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized clinically by symmetrical swelling, induration and thickening of the skin and histologically by thickening of the fascia with chronic inflammatory infiltrate containing eosinophils. The disease is classified in the spectrum morphea/systemic sclerosis and treated with systemic steroids and other immunosuppressant drugs. The purpose of this study was to use extracorporeal photochemotherapy (ECP) in patients with EF to evaluate the effectiveness of this therapy. Three patients affected by EF were treated with ECP because they failed to respond or with contraindications to immunosuppressant treatment. The patients underwent ECP with a UVAR XTS apparatus. Subjects were treated on two consecutive days at 2-week intervals for the first 3 months and thereafter every 4 weeks on the basis of clinical response. The patients were assessed before therapy and then monthly by means of a clinical score. Changes in affected areas were evaluated at predetermined points by computerized skin elastometry (Cutometer SEM 474). After 1 year of therapy we found considerable improvement of clinical parameters in two cases. There was less striking improvement in the other case. These clinical results were confirmed by the elastometry measurements. All patients reported improved quality of life, which enabled a reduction in the dose of immunosuppressants. ECP emerged as a safe and effective therapy in association with low doses of immunosuppressants in our three patients. A randomized comparative multicentre study between ECP as single therapy and ECP plus immunosuppressants and conventional therapies is required to firmly establish photopheresis as a possible basic treatment to combine with conventional therapies for EF.