UK national survey of anticoagulation in extra-corporeal photopheresis-Is it time for a UK consensus statement?

BACKGROUND: Extra-corporeal photopheresis (ECP) requires anticoagulation to prevent circuit clotting. Unfractionated heparin (UFH) is currently the only anticoagulant licensed for the ECP system in use in the United Kingdom (UK). Acid citrate dextrose-A (ACD-A) is the preferred anticoagulant for most other apheresis procedures. Anecdotal evidence suggested variability in ECP practice across the UK with some providers using off-label ACD-A. AIMS: We developed a survey together with the UK Photopheresis Society to establish current practice. MATERIALS & METHODS: This was distributed to all 17 ECP providers covering 34 UK sites. RESULTS: Significant variability in practice was demonstrated with only 36% of responding providers (5/14) using UFH exclusively and 29% (4/14) using ACD-A as standard. CONCLUSION: This survey highlights the need for a UK consensus.

Low-density neutrophils in chronic graft versus host disease (cGVHD) are primarily immature CD10- and enhance T cell activation.

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogeneic haematopoietic stem cell transplantation. Low density neutrophils (LDNs) in autoimmunity, which shares disease features with cGVHD, are proinflammatory, whereas those in cancer and sepsis suppress T cell immunity. Mature LDNs can be distinguished from immature LDNs on the basis of expression of CD10 and suppressive neutrophils can be identified using lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. The functionality of LDNs in cGVHD has not been specifically investigated. Here, we have determined the relative contribution of immature and mature neutrophils to LDNs in cGVHD and assessed whether these were suppressive or potentially proinflammatory. Peripheral blood LDNs and normal density neutrophils (NDNs) from 30 cGVHD patients and NDNs from 10 healthy controls (HCs) were immunophenotyped by flow cytometry. The ability of LDNs and NDNs to influence T cell proliferation and cytokine production in co-cultures was quantified. To further characterize LDNs, their propensity to undergo constitutive apoptosis and differentiate ex vivo was assessed. LDNs were elevated in cGVHD versus HCs, heterogeneous in phenotype, with a predominance of immature CD10- cells in most patients, but some mature CD10+ LOX-1+ LDNs were also detected. LDNs enhanced autologous T cell proliferation, interleukin (IL)-6 and interferon (IFN)-γ production. LDN, but not NDN, CD10 expression was inversely correlated with LOX-1, which correlated with IL-6 production. LDNs resisted apoptosis and differentiated into antigen-presenting/neutrophil-hybrid-like cells, which co-expressed major histocompatibility complex (MHC) class II HLA-DR and immuno-inhibitory programmed cell death ligand 1 (PD-L1), but did not suppress T cell proliferation. These data suggest LDNs in cGVHD are predominantly immature, proinflammatory and may have pathogenic potential.

Role of Physical Therapy before and after Hematopoietic Stem Cell Transplantation: White Paper Report.

Hematopoietic stem cell transplantation (HSCT) patients can suffer from various musculoskeletal problems resulting in long-term functional incapacity. Physical therapy (PT), as a part of the healthcare team, has been historically advocated for regaining functional capacity and improving quality of life post-HSCT. Because of the nature of this condition and the burden of post-transplant complications, this patient group requires a unique approach toward their rehabilitation that takes into account their complex musculoskeletal presentation ranging from fascia, muscle, tendons, bones, and ligaments. However, to our knowledge there is no universal standardized PT protocol or pathway to help guide rehab specialists to achieve optimal gains for this patient group, and anecdotal evidence suggests that these patients do not always receive the PT care they require. Hence, in collaboration with the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation, the Survivorship Special Interest Group of the American Society of Blood and Marrow Transplantation, and the Quality of Life Committee of the Eastern Mediterranean Blood and Marrow Transplantation, herein the Physical Therapy Association for Graft Versus Host Disease provides a brief review on role of PT in mitigating musculoskeletal complications in HSCT patients and makes evidence-based recommendations for incorporation of PT into routine HSCT care.

A case review of a patient experience of photopheresis using a peripherally inserted central catheter.

Extracorporeal photopheresis (ECP) is a cell based immunomodulatory therapy in which the patient is attached intravenously to a cell separating machine. During ECP a patient's blood is collected via either a central venous access device (CVAD) or a peripherally inserted 16G arterial venous fistula needle in either one or both antecubital fossa. However, patients presenting for ECP with GVHD repeatedly present a challenge to the ECP team due to poor venous access resulting from previous therapies and skin changes. The use of peripherally inserted central venous catheters (PICCs) offers an alternative route of vascular access for this cohort of patients. Here we present a case report of a patient successfully treated with ECP following the insertion of a PICC line.

Adrenal insufficiency of patients with graft versus host disease treated with extracorporeal photopheresis.

Graft versus host disease (GvHD) is a serious and common complication of allogenic haematopoietic stem cell transplant. Corticosteroids are considered the standard care for initial treatment of GvHD but a significant proportion of patients will need long-term steroid treatment for control of GvHD. Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory therapy that is an accepted second line treatment in patients with steroid refractory, dependent or intolerant GvHD and has shown efficacy in allowing steroid dose reduction and discontinuation in this cohort of patients. Adrenal cortical insufficiency is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids leading to a severe and potentially life-threatening condition. The most common cause of drug-induced adrenal insufficiency is the suppression of the hypothalamic-pituitary-adrenal axis by exogenous glucocorticoid doses ≥5 mg prednisolone equivalent for more than 4 weeks. The aim of the study was to ascertain the number of patients with GvHD receiving ECP that are affected by adrenocortical insufficiency.

Monitoring lung function in patients with chronic graft versus host disease: a pilot study.

Bronchiolitis obliterans syndrome (BOS) following allogenic haematopoietic stem cell transplant is considered the manifestation of chronic graft versus host disease (cGvHD) in the lung, and affects about 14% of patients with cGvHD, mainly in the first 2 years after transplant. Despite advances in assessment, diagnosis and treatment, the clinical prognosis remains poor for patients with pulmonary manifestations of cGvHD. A pilot study of 50 patients was devised to establish whether a relationship exists between forced expiratory volume in 1 second (FEV1) via pulmonary function test (PFT) and the equivalent peak expiratory flow (PEF) via peak flow handheld spirometry in cGvHD patients receiving extracorporeal photopheresis (ECP). Only PEF observed within 2 days of PFT could be compared with data at month 3, 6, 9 and 12. This pilot study illustrated that monitoring via handheld peak flow readings has the potential to become an acceptable method of monitoring lung function longitudinally in cGvHD patients.

Acute graft v host disease: developing an extracorporeal photopheresis outreach service.

Acute graft v host disease (AGVHD) is the main complication and cause of non-relapse mortality following allogenic hematopoietic stem cell transplantion. It occurs when donor immune cells attack host tissues. The three main organs that AGVHD affects are skin, liver and gastrointestinal tract, with one or more organs being involved. Extracorporeal photopheresis (ECP) is a second-line treatment for AGVHD in patients who fail to respond to high-dose steroids. It is an immuno-modulatory rather than immunosuppressive therapy. However, ECP is only available in a limited number of regional centres. This article describes how an ECP outpatient unit developed and implemented a fast-response ECP outreach facility for a referring hospital with the aim of improving access to treatment for this patient group.

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.

Extracorporeal 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.

Comparison of the CELLEX™ and UVAR-XTS™ closed-system extracorporeal photopheresis devices in the treatment of chronic graft-versus-host disease.

Extracorporeal Photopheresis (ECP) is a cellular immunotherapy frequently used for steroid-refractory graft-versus-host disease (GVHD). Chronic GVHD (cGVHD), response to ECP is associated with survival benefit. The UVAR-XTSTM system and the more recently developed CELLEXTM device (both TherakosTM ) are the mainstay for ECP-delivery in the UK and US. No comparison of treatment outcomes has been reported. We retrospectively compared cGVHD response and steroid reduction and withdrawal in patients treated exclusively over 12 months with either the XTS (n = 51) or CELLEX (n = 50). Our hypothesis was that there would be no difference in clinical outcome or steroid changes in the 2 matched cohorts. We also compared infection incidence, infection-related death (IRD), and treatment time. Significant clinical improvement and regular capacity to reduce or cease steroids was encountered in both cohorts; at 6 months of ECP 70% of cutaneous cGvHD patients had partial or complete responses and 85% of patients receiving steroids pre-ECP had reduced dosage. In the XTS group we unexpectedly encountered both superior steroid reduction (86% dose at least halved vs. 61% for CELLEX, P = 0.01) and withdrawal (15 vs. 5 CELLEX, P = 0.01) and a trend for superior skin disease response in the CELLEX-treated cohort at 3 months. No inter-relationship was evident. Halving or greater reduction of steroid dose by 3 or 6 months was associated with reduced risk of IRD in the XTS cohort as was withdrawal at 6 months for the combined cohorts. By 6 months, XTS-treated patients had experienced fewer antibiotic-requiring infections (mean 1.9 vs. 2.8, P = 0.025). Origins for the disparities are unclear and warrant investigation.

Implementation and evaluation of a pre-assessment telephone triage system in an outpatient photopheresis service.

The prompt assessment of patients as fit for photopheresis is imperative to ensure delivery of a safe and efficient service. Before January 2015 the photopheresis unit was reliant on patients contacting the department directly to cancel their appointment if they were unwell or were suffering from any pre-defined exclusion criteria. Methods to reduce the number of cancellations and patients arriving unwell were therefore examined. The authors combined aspects of patient pre-assessment with telephone triage to develop a system that could provide better care and improve the use of resources within the department. The pre-assessment telephone triage system successfully reduced cancellations and increased patient awareness of conditions that would prevent delivery of photopheresis treatment. Subsequently the quality improvement initiative established that the pre-assessment telephone triage system saved the photopheresis unit over £33 000 over a 12-month period.

The introduction and evaluation of a pressure ulcer risk assessment tool for photopheresis outpatients.

Chronic graft-versus-host disease (cGVHD) patients are at high risk of compromised skin integrity, and of developing pressure ulcers, which may bleed and/or become infected. The Rotherham Outpatient Screening Tool (ROST) was adapted from the Waterlow score and the Malnutrition Universial Screening Tool (MUST) to suit patients attending an outpatient unit for photopheresis. A review of the screening tool highlighted patients at a higher risk of developing pressure damage during treatment and therefore the unit was able to reduce this risk by the provision of a pressure-relieving cushion (Repose).

Improving the service for patients receiving extracorporeal photopheresis using Lean principles.

The photopheresis unit where the authors work has seen an increased demand both locally and as an outreach service. A Lean assessment of the unit was undertaken to improve processing time and productivity, which in turn would improve the availability of treatment and improve patient care. The assessment indicated that there were excellent nursing standards and patient care; however, patient waiting times and treatment times were prolonged in comparison with other units. The unit reviewed the patient pathway and identified where delays occurred and consequently changed patient scheduling.

Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD).

As the use of hematopoietic stem cell transplantation (HSCT) has become a more widespread and effective treatment for hematological malignant and non-malignant conditions, the need to minimize the harmful effects of graft- vs.-host disease (GvHD) has become more important in achieving good outcomes. With diagnosis of GvHD reliant on its clinical manifestations, research into biomarkers for the diagnosis, progression, and even for the prediction of disease, is imperative to combating the high levels of morbidity and mortality post-HSCT. Despite the development of novel treatment approaches to GvHD, corticosteroids remain the standard first-line treatment, with immunosuppressant therapies as second-line options. These strategies however have significant limitations and associated complications. Extracorporeal Photopheresis (ECP) has shown to be effective and safe in treating patients with symptomatic GvHD. ECP has been shown to have varied effects on multiple parts of the immune system and does not appear to increase the risk of relapse or infection in the post HSCT setting. Even so, ECP can be logistically more complex to organize and requires patients to be sufficiently stable. This review aims to summarize the potential role of biomarkers to help guide individualized treatment decisions in patients with acute and chronic GvHD. In relation to ECP, robust biomarkers of GvHD will be highly useful in informing patient selection, intensity and duration of the ECP schedule, monitoring of response and other treatment decisions alongside the concurrent administration of other GvHD therapies. Further research is warranted to establish how GvHD biomarkers are best incorporated into ECP treatment pathways with the goal of tailoring ECP to the needs of individual patients and maximizing benefit.

A survey of extracorporeal photopheresis treatment in pediatric patients in the United Kingdom.

Extracorporeal photopheresis (ECP) is a second-line therapy in acute and chronic GVHD and solid organ transplant rejection. We report ECP use in 98 pediatric patients in seven UK centers from 2010 to 2017, the majority treated for aGVHD (73.5%). ECP was safe and well tolerated including in low body weight patients. Most patients were on multiple immunosuppressive therapies prior to ECP; 45.9% were able to reduce or stop immunosuppression with treatment. Complete or partial response was reported in almost 60%. This study supports the need to include ECP treatment data to national transplant databases to provide accurate information regarding service provision, patient outcomes, and safety.