Real-world clinical characterization, healthcare resource utilization and productivity loss in chronic graft versus host patients exposed to extracorporeal photopheresis in Sweden.

BACKGROUND: Extracorporeal photopheresis (ECP) is frequently used to treat moderate-severe chronic graft versus host disease (cGVHD), however limited data exists describing ECP treatment effects on healthcare and societal costs. We aimed to characterize clinical and health economic outcomes and productivity loss in cGVHD patients exposed to ECP. METHODS: We identified 2708 patients aged ≥ 18 years with a record of allogeneic hematopoietic stem cell transplantation (HSCT) in the Swedish Patient Register between 2006 and 2020. Patients exposed to ECP from 3-months post HSCT (index) were included (n= 183). Data was linked to the Prescribed Drug Register, the Cause of Death Register, and the Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA). RESULTS: The median patient age at index was 51 years (IQR1-3; 38-61). In the 3-month period before ECP initiation compared to 9-12 months post-ECP, the cumulative three-month dose per patient decreased prednisolone/prednisone (1,381 mg vs. 658 mg, p < 0.001) and cyclosporin (12,242 mg vs. 3,501 mg, p < 0.001). Infection incidence also decreased over the same period (79.2% vs 59.1%, p < 0.001). Time spent in healthcare decreased from 68.9% to 22.1% from the first and fifth follow-up year respectively, and corresponding annual healthcare cost reduced from €27,719 to €1,981. Among patients < 66 years of age, sickness-related workplace absence decreased from 73.2% to 31.9% between the first and fifth follow-up year, with median annual productivity loss decreasing from €20,358 to €7,211 per patient. CONCLUSIONS: ECP was associated with reduced use of corticosteroids, immunosuppressive agents, and fewer infections. Furthermore, cost and healthcare utilization decreased over time.

The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

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.

Granulocyte concentrates prepared from residual leukocyte units produced by the Reveos automated blood processing system.

BACKGROUND: Granulocyte concentrates are mainly derived by apheresis technique from donors stimulated with granulocyte colony-stimulating factor and steroids. The automated blood processing system Reveos, which is now increasingly used across the world, separates whole blood into four components, including a residual leukocyte unit containing granulocytes. The aim of this study was to produce an alternative granulocyte concentrate from leukocyte units produced by the Reveos system, and to assess the function of the granulocytes. METHODS: The number of granulocytes was measured in residual leukocyte units, derived from whole blood donations, with different volumes ranging from 10 to 40 ml. After deciding the optimal volume of the leukocyte unit (30 ml), ten ABO-matched units were pooled to form a granulocyte concentrate. The function of the granulocytes from residual leukocyte units was assessed by analyzing surface markers, phagocytosis of yeast, and production of reactive oxygen species. RESULTS: Residual leukocyte units with a volume of 30 ml contained a median number of 0,7 × 109 granulocytes, and granulocyte concentrates prepared from ten pooled 30 ml-leukocyte units contained a median number of 6,3 × 109 granulocytes. Granulocytes derived from residual leukocyte units displayed surface markers associated with granulocyte function, and capability to phagocytose yeast and produce reactive oxygen species. CONCLUSIONS: Granulocyte concentrates prepared from residual leukocyte units contain in vitro functional granulocytes and may be considered as an alternative product in acute situations before regular granulocyte concentrates from stimulated donors are available.

Storage-induced change in platelet transfusion response evaluated by serial transfusions from one donor to one patient.

BACKGROUND: Storage of platelet concentrates (PCs) results in storage lesions with possible detrimental effects on platelet recovery after transfusion, which might affect their ability to prevent or arrest bleeding. The aim of this study was to compare the quality of PCs stored for 1 to 3 or 5 to 7 days by assessing the corrected count increment (CCI) after transfusion. To isolate the effects of storage time, we studied serial transfusions of PCs obtained from one donor and one donation, and transfused to one single recipient after storage for 1 to 3 days and 5 to 7 days. STUDY DESIGN AND METHODS: Platelets were obtained from one donor by apheresis, divided into two units (>240 × 109 platelets/unit) and stored for 1 to 3 and 5 to 7 days, respectively, before transfusion. The PCs were transfused on normal indications to patients undergoing treatment at the hematology ward. Platelet count was measured before and after transfusion. RESULTS: Thirty patients concluded the study according to the protocol. The mean storage time was 2.4 ± 0.7 and 5.7 ± 0.8 days for platelets transfused on Days 1 to 3 and 5 to 7, respectively. Storage for 5 to 7 days decreased the 1-hour transfusion response as compared to platelets stored 1 to 3 days, from a CCI of 17 ± 7 to 13 ± 5. Despite this decrease, 86% of the 5 to 7 days stored PCs resulted in a CCI above the cutoff value for a successful transfusion of 7.5, which was not significantly different to PCs stored for 1 to 3 days. CONCLUSION: Storage of PCs for 5 to 7 days only slightly altered the transfusion response.

Does prophylactic calcium in apheresis cause more harm than good? - Centre heterogeneity within the World Apheresis Association Register prevents firm conclusions.

BACKGROUND AND OBJECTIVES: Symptomatic hypocalcaemia is common during apheresis procedures based on citrate-based anticoagulants. As a consequence, patients often receive prophylactic calcium treatment. However, a recent publication based on the World Apheresis Association (WAA) register suggested harmful effects of such prophylactic calcium use. Recognizing possible limitations in the previous WAA register analyses, we critically re-evaluate the data, to test whether a change in prophylactic calcium usage may be warranted. MATERIALS AND METHODS: Using the WAA register, we reanalysed previous data by means of centre and treatment type stratification, to explore the role of prophylactic calcium as a risk factor for adverse events. RESULTS: There was large variability in adverse event rates dependent on the centre performing the apheresis procedure and dependent on the type of procedure. When this variability was accounted for, there was no clear effect of calcium administration on risk of adverse effects. CONCLUSION: Shortcomings in the previous WAA register analyses may have failed to account for important confounding factors resulting in a substantial overestimation of the risk attributable to calcium usage. Overall our findings do not support a negative effect of prophylactic calcium administration in the apheresis setting.

Treatment of platelet concentrates with ultraviolet C light for pathogen reduction increases cytokine accumulation.

BACKGROUND: Pathogen reduction technologies use photoactive substances in combination with ultraviolet (UV) light to inactivate pathogens. A new method uses only UVC light for pathogen reduction. This study assesses the effects of UVC light treatment on cytokine release in platelet (PLT) concentrates (PCs). STUDY DESIGN AND METHODS: A PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three such PCs were pooled and divided into 3 units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light technology. Ten units of each type were investigated. Cytokine release was analyzed on Days 1, 5, and 7 of storage. Correlation between cytokines, PLT surface markers, and hemostatic properties was investigated. RESULTS: Swirling was well preserved and pH was above the reference limit of 6.4 during storage of PLTs in all groups. Cytokine levels increased during storage in all groups but to a larger degree in PCs treated with UVC light. Only weak correlation was found between cytokines and PLT surface markers (r < 0.5). However, several cytokines showed strong correlation (r > 0.6) with the PLTs' ability to promote clot retraction. CONCLUSION: UVC treatment resulted in increased release from PLT alpha granules as evident by a higher cytokine release compared to nonirradiated and gamma-irradiated PCs. The clinical relevance of these findings needs to be further evaluated.

In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma-irradiated platelets.

BACKGROUND: During storage of platelet concentrates (PCs) replication of contaminating pathogens might occur, which can be prevented by various pathogen inactivation (PI) methods using photoactive substances in combination with ultraviolet (UV) light. A new method uses only UVC light for PI without photoactive substances. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of platelets (PLTs) treated with UVC light. STUDY DESIGN AND METHODS: A PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three PCs were pooled and divided into 3 units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light. In vitro variables including analysis of coagulation by free oscillation rheometry were analyzed on Days 1, 5, and 7 of storage. Ten units in each group were investigated. RESULTS: Swirling was well preserved, and the pH level was higher than the reference limit (6.4) during storage of PLTs in all groups. Glycolysis and PLT activation were higher for UVC-treated PLTs but the clot-forming capacity was unaffected. However, immediately after UVC treatment, the clot elastic properties were slightly affected. Hypotonic shock response decreased immediately after UVC treatment but recovered partly during the storage period. CONCLUSION: UVC treatment affected the in vitro properties, but PLT quality and storage stability were well preserved for up to 7 days, and the in vitro hemostatic capacity of UVC-treated PLTs was only minimally altered. The clinical relevance of these changes needs to be evaluated in controlled trials.

In vitro properties of platelets stored in a small container for pediatric transfusion.

BACKGROUND: The quality of a platelet (PLT) concentrate (PC) is affected by the number of PLTs in relation to the size and gas permeability of the container. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of PLTs stored in a container of standard or small size. STUDY DESIGN AND METHODS: PCs with 30% plasma and 70% PLT additive solution were prepared from buffy coats. Two PCs were pooled and divided into the following containers: 1 unit and ½ a unit into a 1.8-L container (reference container) and ½ a unit into a 0.45-L container (test container). In a second set of experiments » of a unit was stored in the reference and test containers. Swirling, PLT count, blood gases, metabolic variables, PLT activation markers, hypotonic shock response (HSR), and coagulation by free oscillation rheometry were analyzed during 7 days of storage. RESULTS: Swirling was well preserved and pH was acceptable (6.4-7.4) during storage of PLTs in both containers. Glycolysis and PLT activation were higher when storing ½ and » of a unit in the reference container and storage of » of a unit in the reference container resulted in the largest decrease in HSR. The clotting time was similar whereas the clot elasticity was slightly lower for PLTs when stored as ½ and » of a unit in the reference container. CONCLUSION: Storage of a low number of PLTs benefits by storage in a small container in terms of better maintained in vitro properties.