UK national audit of extracorporeal photopheresis (ECP) in chronic graft versus host disease
Leukemia & lymphoma. 2020;:1-4
European dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2
Journal of the European Academy of Dermatology and Venereology : JEADV. 2020
BACKGROUND Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-vs.-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T-cell lymphoma, chronic graft-vs.-host disease and acute graft-vs.-host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.
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.
Adult patients with skin-predominant acute GvHD (n=37)
Extracorporeal photopheresis (ECP) in addition to low-dose corticosteroids
Overall response rate was 81% after a median of three ECP procedures, 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, 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.
Retrospective multicenter study of extracorporeal photopheresis in steroid-refractory acute and chronic graft-versus-host disease
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
BACKGROUND Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory GvHD. This study's main objectives were to analyze the clinical response and impact of ECP therapy in steroid dose reduction. STUDY DESIGN AND METHODS A retrospective observational series of 113 patients from 7 transplant centers was analyzed. 65 patients (58%) had acute GvHD (aGvHD) and 48 (42%) chronic GvHD (cGvHD). All ECP procedures were performed with the off-line system. RESULTS The median number of procedures until initial response was 3, for both aGvHD and cGvHD. ECP was the second-line therapy in 48% of aGvHD cases and 50% in cGvHD. 71% of the cases of aGvHD were grade 3-4 and 69% of the cases of cGvHD were severe. The overall response rate on day 28 in aGvHD was 53% (CR 45%), whereas in cGvHD it was 67% (CR 23%). Skin was the most involved organ, with a response rate of 58% (CR 49%) in aGvHD and 69% (CR 29%) in cGvHD. At the end of ECP treatment, 60% of patients treated for aGvHD that responded were able to stop steroids, with a median dose reduction of 100%. Significant OS differences were observed for patients responding to ECP in aGvHD (HR=4.3, p<0.001) and cGvHD (HR=4.8, p=0.003) patients. CONCLUSIONS ECP is a valid therapeutic alternative in patients with steroid-refractory acute and chronic GvHD, permitting significant steroid dose reductions.
Patients with haematological malignancies, with steroid-refractory GvHD following allo-SCT (n=113)
Patients with acute GvHD (aGvHD, n=65) were compared with patients with chronic GvHD (cGvHD, n=48)
The overall response rate on day 28 in aGvHD was 53% (CR 45%), whereas in cGvHD it was 67% (CR 23%). Skin was the most involved organ, with a response rate of 58% (CR 49%) in aGvHD and 69% (CR 29%) in cGvHD. At the end of ECP treatment, 60% of patients treated for aGvHD that responded were able to stop steroids, with a median dose reduction of 100%. Significant OS differences were observed for patients responding to ECP in aGvHD and cGvHD patients.
Extracorporeal photopheresis for graft versus host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group
European journal of haematology. 2020
Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft versus host disease (GvHD), with a good effect to side effect profile. In this review we present a summary of present literature and provide evidence-based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonization and evidence based practise. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head to head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low-moderate (GRADE) and encourage future prospective multi-armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardized treatment schedules and regular follow-up are imperative to ensure the best possible patient outcome.
Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis
Central-European journal of immunology. 2019;44(1):84-91
Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response. Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison. Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment. Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.
Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease
Blood advances. 2019;3(7):969-979
Chronic graft-versus-host disease (cGVHD) affects >50% of hematopoietic stem cell transplant patients. Extracorporeal photopheresis (ECP), an immunomodulatory therapy, provides clinical benefit in steroid-refractory (SR) cGVHD, possibly via regulatory T (Treg) and natural killer (NK) cell expansion. We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential Treg and NK-cell expansion with minimal effect on conventional T (Tcon) cells. We evaluated the effect of ECP (weeks 1-16) plus IL2 (1 x 10(6) IU/m(2), weeks 9-16) in 25 adult patients with SR-cGVHD in a prospective phase 2 trial. Objective responses occurred in 29% and 62% of evaluable patients at weeks 8 (ECP alone) and 16 (ECP plus IL2), respectively. Eight weeks of ECP alone was associated with a marked decline in CD4(+) Tcon (P = .03) and CD8(+) T cells (P = .0002), with minimal change in Treg cells, Treg:Tcon cell ratio, or NK cells. Adding IL2 induced an increase in Treg cells (P < .05 at weeks 9-16 vs week 8), Treg:Tcon cell ratio (P < .0001 at weeks 9-16 vs week 8), and NK cells (P < .05 at weeks 9-16 vs week 8). Patients responding to ECP alone had significantly fewer CD4(+) Tcon and CD8(+) T cells at baseline compared with patients who responded after IL2 addition and patients who did not respond; neither Treg nor NK cells were associated with response to ECP alone. Altogether, ECP plus IL2 is safe and effective in patients with SR-cGVHD. ECP and IL2 have distinct immunologic effects, suggesting different therapeutic mechanisms of action. This trial was registered at www.clinicaltrials.gov as #NCT02340676.
Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis
Journal of clinical apheresis. 2019
BACKGROUND Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). CONCLUSIONS Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.
Efficacy and safety of one-day offline extracorporeal photopheresis schedule processing one total blood volume for treating patients with graft-versus-host disease
BACKGROUND Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule. STUDY DESIGN AND METHODS Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures. RESULTS Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively. CONCLUSION Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe.
Inline extracorporeal photopheresis: evaluation of cell collection efficiency
BACKGROUND Extracorporeal photopheresis (ECP) therapy has proved to be an effective and safe treatment for graft-versus-host-disease (GvHD), an important complication after hematopoietic stem cell transplantation. In 2016, we acquired Therakos CellEx, a dedicated inline ECP device to accomplish a significant increase in ECP activity. In literature, we found few data reporting CellEx performance evaluated in terms of collection efficiency to qualify the device. Hence, we decided to collect and analyze our data in order to build a reference in terms of expected results of the procedure. Here we report our data of ECP performed using CellEx in a 12-month period focusing on collection efficiency assessment, as well as procedural and apheretic product characteristics. STUDY DESIGN AND METHODS We collected data of patients undergoing ECP from April 2018 to March 2019 using CellEx in order to evaluate collection efficiency. RESULTS Between April 2018 and March 2019 we treated 28 adult patients affected by GvHD performing 319 ECP using CellEx. CellEx mononuclear cell product was characterized by high mononuclear cell percentage and low percentage of granulocytes, resulting particularly suitable for ECP treatments. Median collection efficiency for total nucleated cells and for mononuclear cells was 31.2% and 62.3%, respectively. CONCLUSION Collection efficiency of CellEx was comparable to that usually obtained by cell separators designed for cell collection and was comparable to that of offline systems. Our results provide a detailed performance evaluation for inline ECP system users.