Reinforcement of the Standard Therapy with Two Infusions of Convalescent Plasma for Patients with COVID-19: A Randomized Clinical Trial.

BACKGROUND: The aim was to evaluate the reinforcement of the standard therapy with hyperimmune plasma (HP) in Coronavirus-19 disease (COVID-19) patients. METHODS: Open-label, multicenter, randomized clinical trial performed in three hospitals in the Balearic Islands. Non-severe COVID-19 hospitalized patients with clinical time evolution equal to/less than 7 days were included, and randomized in: plasma group (PG) (n = 37), receiving 600 mL divided into two doses from convalescent plasma donor, administered on days 1 and 2 after the enrollment; and control group (CG) (n = 17). Primary outcome was the time for clinical improvement within 21 days, defined as patient achievement of categories 8, 7, and 6 in the Adaptive COVID-19 Treatment Trial scale (ACTT). The trial was terminated early due to the impossibility of recruitment due to the pandemic. RESULTS: PG presented better scores on the ACTT scale at 7 days after HP infusion, whereas CG was needed 14 days to achieve similar results. The plasma infusion was safe. CONCLUSIONS: Despite the tendency observed in the plasma group to achieve slightly earlier better physical condition compared with the standard treatment alone. The administration of HP has been shown to be a safe therapy. No robust evidence was found to affirm a therapeutic effect of the early administration of two infusions of HP for non-severe COVID-19 infected patients. The interpretation is limited by the early termination of the trial, which resulted in a small sample size.

Cryopreservation of platelets treated with riboflavin and UV light and stored at -80°C for 1 year.

BACKGROUND: The combination of pathogen reduction technologies (PRTs) and cryopreservation can contribute to building a safe and durable platelet (PLT) inventory. Information about cryopreserved riboflavin and UV light-treated PLTs is scarce. STUDY DESIGN AND METHODS: Twenty-four buffy coat (BC) PLT concentrates were grouped into 12 type-matched pairs, pooled, and divided into 12 non-PRT-treated control units and 12 riboflavin and UV light PRT-treated test units. Both were cryopreserved with 5% DMSO and stored at -80°C for 1 year. The cryopreservation method used was designed to avoid the formation of aggregates. PLT variables (PLT recovery, swirling, pH, MPV, and LDH) and hemostatic function measured by thromboelastography (TEG) were analyzed before cryopreservation (day 1) and post-cryopreservation at day 14 and months 3, 6, and 12 of storage at -80°C. The analyses were carried out within 1-h post-thaw. RESULTS: No aggregates were found in either PLT group at any time. Swirling was observed in both groups. MPV increased and mean pH values decreased over time (p < .001), but the mean pH value was never below 6.4 in either group after 12 months of storage at -80°C. PLT recovery was good and clotting time became significantly shorter over the storage period in both groups (p < .001). CONCLUSION: Our cryopreservation and thawing method prevented aggregate formation in cryopreserved riboflavin-UV-light-treated PLTs, which exhibited good recovery, swirling, pH > 6.4, and procoagulant potential, as evidenced by a reduced clotting time after 12 months of storage at -80°C. The clinical relevance of these findings should be further investigated in clinical trials.

Haemostatic function measured by thromboelastography and metabolic activity of platelets treated with riboflavin and UV light.

BACKGROUND: Pathogen reduction technology (PRT) may damage platelet (PLT) components. To study this, metabolic activity and haemostatic function of buffy coat (BC) PLT concentrates, with or without riboflavin and UV light PRT treatment, were compared. MATERIAL AND METHODS: Twenty-four BC PLT concentrates, leukoreduced and diluted in additive solution, were grouped into 12 type-matched pairs, which were pooled and divided into 12 non-PRT-treated BC PLT concentrates (control units) and 12 riboflavin and UV PRT-treated BC PLT concentrates (test units). Haemostatic function and metabolic parameters were monitored by thrombelastography at days 1, 3, 7 and 14 post collection in both PLT groups. RESULTS: Loss of PLT discoid shape, glucose consumption, lactate production, and decrease in pH were greater in the PRT-treated PLTs than in control PLTs over time (p<0.001). PLT haemostatic function evaluated by clot strength was also significantly weaker in PRT-treated PLTs compared with the excellent clot quality of control PLTs at day 7 (maximum amplitude: 41.27 vs 64.27; p<0.001), and even at day 14 (21.16 vs 60.39; p<0.001) of storage. DISCUSSION: Pathogen reduction technology treatment accelerates and increases platelet storage lesion, resulting in glucose depletion, lactate accumulation, PLT acidification, and discoid shape loss. The clots produced by control PLTs at day 14 were still remarkably strong, whereas at day 7 PRT-treated PLTs produced weaker clots compared to the control group. Clinical trials investigating the efficacy of PRT-treated PLTs transfused at the end of the storage period (day 7), when the in vitro clot strength is weaker, are needed.

Differential Impact of Relative Dose-Intensity Reductions in Diffuse Large B-Cell Lymphoma Treated with R-CHOP21 or R-CHOP14.

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.

Role of Riboflavin- and UV Light-Treated Plasma in Prevention of Transfusion-Related Acute Lung Injury.

INTRODUCTION: Risk reduction strategies for transfusion-related acute lung injury (TRALI) include the preferential use of male donors to provide fresh frozen plasma (FFP). Implementing this measure based on FFP quarantine program is a very complex process. To improve FFP inventory management and the availability of FFP from male donors, the Mirasol Pathogen Reduction Technology(®) (PRT) system for FFP using riboflavin and UV light was adopted in our region in 2012. METHODS: The percentage of male/female FFP units issued and TRALI cases in patients receiving FFP in the period before implementing riboflavin and UV light (2010-2011) was compared with the period post implementation of riboflavin and UV light (2012-2013). RESULTS: In 2010 and 2011, there was one FFP transfusion-related TRALI case reported per year, when the proportion of male/female FFP distributed to the hospitals was 60/40. During 2012 and 2013, there have been no FFP transfusion-related TRALI cases, when the proportion of male/female FFP distributed to the hospitals was around 97/3. Mirasol PRT allows quick availability (24 h from collection) compared to quarantined FFP (≥3 months from collection). CONCLUSION: Thanks to its readiness, simplicity and feasibility, riboflavin- and UV light-treated FFP implementation can facilitate the preferential use of FFP from male donors as a TRALI prevention strategy.