Potency assessment of IFNγ-producing SARS-CoV-2-specific T cells from COVID-19 convalescent subjects.

The development of new therapies for COVID-19 high-risk patients remains necessary to prevent additional deaths. Here, we studied the phenotypical and functional characteristics of IFN-γ producing-SARS-CoV-2-specific T cells (SC2-STs), obtained from 12 COVID-19 convalescent donors, to determine their potency as an off-the-shelf T cell therapy product. We found that these cells present mainly an effector memory phenotype, characterized by the basal expression of cytotoxicity and activation markers, including granzyme B, perforin, CD38, and PD-1. We demonstrated that SC2-STs could be expanded and isolated in vitro, and they exhibited peptide-specific cytolytic and proliferative responses after antigenic re-challenge. Collectively, these data demonstrate that SC2-STs can be a suitable candidate for the manufacture of a T cell therapy product aimed to treat severe COVID-19.

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective, multicenter study of a large series of patients.

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 106 CD34+ cells/kg) was 1 (range 1-4) and the median PLX administration time before apheresis was 11 h (range 1-18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1-5) and the mean number of CD34+ cells collected was 2.95 × 106/kg (range 0-30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/µL was 11 days (range 3-31) and the median time to platelet recovery >20 × 103/µL was 13 days (range 5-69). At 100 days after auto-HCT, the platelet count was 137 × 109/L (range 7-340), the ANC was 2.3 × 109/L (range 0.1-13.0), and the hemoglobin concentration was 123 g/L (range 79-165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34+ cell concentration on day +4 or low CD34+ cell yield on apheresis.

Addition of plerixafor to G-CSF in poor mobilizing healthy related donors overcame mobilization failure: An observational case series on behalf of the Grupo Español de Trasplante Hematopoyético (GETH).

Plerixafor (Mozobil, Sanofi) is approved for using in patients with lymphoma and multiple myeloma when steady-state mobilization strategies fail. Although off-label use of plerixafor in healthy related donors (HRD) is known, limited data are available and no recommendations exist to guide its use in this setting. With the aim of collecting data from HRDs who received plerixafor in our country, we designed an observational case series study within the Spanish Group of Hematopoietic Transplant and Cell Therapy (GETH). Plerixafor was administered subcutaneously to 30 HRDs at a median dose of 0.24 mg/Kg (interquartile range (IQR): 0.23-0.25) because mobilization failure after using mobilization with G-CSF (mobilization failure was defined as collection of <4.0 × 106 CD34+ cells/Kg recipient). All HRDs received G-CSF at a median dose of 11 µg/Kg/day (IQR: 10-12) for 4-5 days. Leukocytapheresis after G-CSF mobilization was performed in 23 (77 %) HRDs collecting a median of 1.6 × 106 CD34+ cells/Kg recipient weight (IQR: 0.9-2.5). Addition of plerixafor allowed the collection of a higher median number of CD34 cells (4.98 × 106 CD34+ cells/Kg recipient weight (IQR: 3.5-5.8)) when compared with the collection of CD34+ cells with G-CSF alone (p < 0.01). The final median total number of CD34+ cells collected was 6.1 × 106/Kg recipient weight (IQR: 4.8-7.3). Mild adverse events related with plerixafor administration were reported in 8 (27 %) donors. In conclusion, addition of plerixafor after G-CSF mobilization failure in HRDs allowed collecting higher number of CD34+ cells in comparison with steady-state mobilization.

Mobilization of hematopoietic progenitor cells from allogeneic healthy donors using a new biosimilar G-CSF (Zarzio®).

Peripheral blood progenitor cells (PBPCs) have become the major source of hematopoietic progenitor cells for allogeneic transplantation. In February 2008, Zarzio® was approved by the European Medicine Agency for PBPCs mobilization, but this authorization was not based in trials analyzing safety and efficacy for PBPCs mobilization. Since August 2011, Zarzio® has been used at our institution for PBPCs mobilization. In total 36 healthy family donors underwent PBPCs mobilization, 18 with Neupogen® and 18 with Zarzio®. Donor characteristics were equivalent between groups, and no severe adverse effects were registered in the Zarzio® group. The number of CD34 cells collected/Kg recipient body weight was 6.7 × 10(6) (3.8-11.1) in the Zarzio® group versus 8.4 × 10(6) (5.6-16.6) in the Neupogen® group (P = 0.04). We collected the minimal target cell dose (2 × 10(6) /kg) in all donors from each group and no significant differences were found in the collection of the optimal cell dose (5 × 10(6) /kg) between groups, although 3/18 (16.6%) donors that received Zarzio® failed to mobilize the optimal cell dose compared with 0% in the Neupogen® group. A total of 35 patients proceeded to transplantation (17 in the Zarzio® and 18 in the Neupogen® groups, respectively). Platelet and neutrophil median time to engraftment was comparable between the two groups. Our retrospective study supports the conclusion that Zarzio® mobilization of PBPCs in healthy donors is safe but perhaps not as effective as the reference Neupogen. However, more prospective trials are required to definitively asses the safety and efficacy of G-CSF biosimilars for PBPCs mobilization in healthy donors.

Evaluation of the post-transfusion platelet increment and safety of riboflavin-based pathogen reduction technology (PRT) treated platelet products stored in platelet additive solution for 5 days or less versus 6-7 days.

BACKGROUND AND OBJECTIVES: Platelets are stored routinely for 5 days or less and extended platelet storage time could improve product availability. This study compared platelet count increments (CI24hs) of riboflavin plus UV-light (PRT) treated platelet products in platelet additive solution stored for 5 days or less to products stored for 6-7 days. MATERIAL AND METHODS: This was a retrospective study comparing CI24hs between two groups. Hematology patients received PRT treated platelet products stored for <5 days, or for 6-7 days. Platelet counts and adverse events during and up to 24 hours after transfusion were recorded and compared between the groups. RESULTS: Ninety-seven patients received 168 transfusions of <5 day old PRT-treated platelets and 49 patients received 74 transfusions of 6-7 day old PRT-treated platelets. There was no statistically significant difference in CI24hs between the <5 day (median 6000) and 6-7 day storage group (median 8000) (p-value = 0.509). One mild fever was documented in the <5 day storage group. CONCLUSION: CI24hs are similar for PRT-treated PLTs stored in PAS for <5 or 6-7 days. Studies to further evaluate clinical outcomes such as bleeding are ongoing.

Improved traceability and transfusion safety with a new portable computerised system in a hospital with intermediate transfusion activity.

BACKGROUND: A retrospective study carried out on medical records of transfused patients in our hospital in 2002 revealed that manual identification procedures were insufficient to offer satisfactory traceability. The aim of this study was to assess adequacy of transfusion traceability and compliance with proper identification procedures after introducing an electronic identification system (EIS) for transfusion safety. MATERIALS AND METHODS: The chosen EIS (Gricode(®)) was set up. Traceability was calculated as the percentage of empty blood units used returned to the Transfusion Service, compared to the number of supplied units. Compliance in the Transfusion Service was calculated as the percentage of electronic controls from dispatch of blood components/transfusion request performed, compared to the total number of transfused units. Compliance in the ward was calculated as the percentage of electronic controls from sample collection/transfusion performed, compared to the total number of samples collected. RESULTS: This retrospective study showed that only 48.0% of the medical records were free of inaccuracies. After the implementation of the EIS (2005-2008), traceability was always above 99%. Percentage of monthly compliance from 2006 to 2008 was always above 93%, showing a significant trend to increase (p<0.05). The mean compliance in this period was higher in the Transfusion Service (97.8 ± 0.7 SD) than in the ward (94.9 ± 2.4 SD; p<0.001). Compliance in the ward was lowest when the system was first implemented (87.9% in April 2006) after which it progressively increased. No errors in ABO transfusions were registered. CONCLUSION: After implementation of the EIS, traceability and compliance reached very high levels, linked to an improvement in transfusion safety.