Extracorporeal photopheresis for graft-vs-host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group.

Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft-vs-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 harmonisation and evidence-based practice. 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, standardised treatment schedules and regular follow-up are imperative to ensure the best possible patient outcome.

Feasibility of extracorporeal photopheresis in pediatric patients with graft-versus-host disease after hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is a main cause of morbidity and mortality following hematopoietic stem cell transplantation. The cumulative incidence of acute and chronic GVHD (aGVHD, cGVHD) reaches 30%-50% and 20% in pediatric populations, respectively. Prednisolone and/or calcineurin inhibitors (CNI) are first-line treatments, but no superior second-line treatment has yet been established. Several treatments have been suggested, among others extracorporeal photopheresis (ECP). Technical advances have made treatment of pediatric patients possible; however, only few reports on the feasibility of ECP in children have been published. We retrospectively studied the feasibility, safety, and efficacy of ECP in 15 children with steroid-dependent/refractory acute or chronic GVHD, who initiated ECP treatment between April 2014 and January 2018. Only few and mild side effects directly related to the ECP procedure were registered, even in patients with low body weight. The most frequent cause of shortened or canceled ECP treatment was difficulties with vascular accesses, which were more rarely seen using central venous catheters with larger lumens and made of stiffer material. Nine patients had grade II-III aGVHD. Six of these experienced a response to ECP at day 28, while eight of nine had responded at the last ECP treatment. Six patients had cGVHD when ECP was initiated, and of these, four had a partial response at last ECP treatment. We found ECP to be a feasible and safe treatment, and particularly, children with aGVHD appeared to respond well to ECP.

Longitudinal follow-up of response status and concomitant immunosuppression in patients treated with extracorporeal photopheresis for chronic graft versus host disease.

Improvement in chronic graft vs. host disease (cGvHD) following treatment with extracorporeal photopheresis (ECP) has been shown previously. However, the effect is often measured at only one point in time or as best response. Chronic GvHD activity fluctuates over time, so we retrospectively evaluated cGvHD responses in 54 patients with primarily moderate or severe cGvHD throughout the ECP treatment course and after stopping ECP. The dominant response was partial remission (PR) in 33 patients, no change (NC) in 10 patients, progressive disease (PD) in 10 patients and complete remission (CR) in one patient. Response rates and reduction in glucocorticoid dose reached a plateau after nine months. The main reason for stopping ECP was the absence of further improvement. Flares in cGvHD activity were seen in 36 patients. Additional treatment during ECP was administered to 29 patients. Failure free survival with response was achieved for 52% of patients at 6 months and 43% at 1 year. Our study confirms that ECP is a safe option for cGvHD therapy. The majority of the patients experience improvement and reduction in glucocorticoid dose but flares in cGvHD activity and the need for additional immunosuppression are seen frequently.

Evaluation of infliximab as second-line treatment of acute graft versus host disease -validating response on day 7 and 28 as predictors of survival.

Several immunosuppressive drugs have been proposed for second-line treatment of steroid-refractory acute graft versus host disease (aGvHD) after allogeneic hematopoietic stem cell transplantation. However, the studies on these drugs are small, retrospective, uncontrolled and use different endpoints. Therefore, it remains unknown which treatment is superior. We retrospectively evaluated 68 consecutive patients treated with infliximab for aGvHD. We adhered to recently proposed guidelines for aGvHD trials and thus evaluated response on day 7 and 28. Furthermore, we assessed the composite endpoint 6 months freedom from treatment failure (6MFTF). The majority of patients had grade III-IV aGvHD. We found that 41 patients (60%) responded on day 7 and 31 patients (46%) on day 28. Twenty-four patients (35%) achieved 6MFTF. The main reasons for failure within 6 months were death (n = 31) or additional immunosuppression (n = 16). By six and 24 months, 44 and 34% of the patients were alive respectively. Patients with response to infliximab on day 7 and 28 had significantly higher overall survival (OS) probability than non-responders. We show that response on day 7 and 28 identifies high and low risk groups. Patients who fail to respond should be identified early and offered alternative therapy.

Haemoglobinopathia Ypsilanti - A rare, but important differential diagnosis to polycythaemia vera.

We present a case of a mother and daughter who were initially diagnosed with polycythaemia vera and treated with venesectio. As JAK2 V6217F/exon 12 mutation analyses became available, these were performed and turned out negative. Haemoglobin electrophoresis was performed and the patients were found to have high oxygen affinity haemoglobin Ypsilanti. It is important and relevant to look for high oxygen affinity variants of haemoglobin when there is a family history of erythrocytosis, in young persons and when there is no apparent reason or clonal marker present.