Donor-Specific Anti-HLA Antibodies in Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: Risk of Graft Failure, Poor Graft Function, and Impact on Outcomes.

The presence of donor-specific anti-HLA antibodies (DSA) is associated with a 10-fold increased risk of graft failure in haploidentical stem cell transplantation (haplo-SCT). Consensus guidelines from the European Society for Blood and Marrow Transplantation set a mean fluorescence intensity (MFI)1000 as a cutoff for DSA positivity. In the absence of an alternative donor, it is recommended that patients undergo desensitization therapy, especially with high DSA levels (5000 MFI). The aim of this study was to analyze the impact of DSA on risk of graft failure and poor graft function, as well as on major outcomes in a consecutive cohort of patients who were systematically screened for DSA before haplo-SCT. A total of 141 consecutive patients were candidates for unmanipulated haplo-SCT with post-transplantation cyclophosphamide (PT-Cy) at our center between January 2012 and January 2018, and 135 were analyzed for the presence of HLA antibodies. Of these 134 patients underwent haplo-SCT. HLA antibodies were detected in 40 patients, including 19 with DSA and 21 without DSA. Ten of the 19 patients with DSA underwent transplantation using that donor, whereas 2 underwent a desensitization program before transplantation. Only 2 patients experienced primary graft failure (1.4 %), both of whom were without DSA. Twenty patients developed a poor graft function (15%). The 3-year overall survival (OS), 3-year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were analyzed according to the presence or absence of DSA. No statistically significant difference was found. No impact of the presence of DSA on the risk of developing graft failure and poor graft function was revealed. Major outcomes of transplantation were analyzed separately in patients with poor graft function and those with good graft function. The 3-year OS, 3-year PFS, and 1-year NRM in good graft function and poor graft function populations were 62% versus 20% (P.0001), 53% versus 20% (P.0001), and 12% versus 40% (P = .009), respectively. The presence of low-level DSA in the absence of desensitization did not correlate with the risk of developing graft failure and poor graft function. Patients who experienced poor graft function had worse outcomes than patients with good graft function

Effect of a Third Dose of SARS-CoV-2 mRNA BNT162b2 Vaccine on Humoral and Cellular Responses and Serum Anti-HLA Antibodies in Kidney Transplant Recipients

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely impacted on public health, mainly on immunosuppressed patients, including solid organ transplant recipients. Vaccination represents a valuable tool for the prevention of severe SARS-CoV-2 infection, and the immunogenicity of mRNA vaccines has been evaluated in transplanted patients. In this study, we investigated the role of a third dose of the BNT162b2 vaccine in a cohort of kidney transplant recipients, analyzing both humoral and cell-mediated responses. We observed an increased immune response after the third dose of the vaccine, especially in terms of Spike-specific T cell response. The level of seroconversion remained lower than 50% even after the administration of the third dose. Mycophenolate treatment, steroid administration and age seemed to be associated with a poor immune response. In our cohort, 11/45 patients experienced a SARS-CoV-2 infection after the third vaccine dose. HLA antibodies appearance was recorded in 7 out 45 (15.5%) patients, but none of the patients developed acute renal rejection. Further studies for the evaluation of long-term immune responses are still ongoing, and the impact of a fourth dose of the vaccine will be evaluated

Photopheresis Abates the Anti-HLA Antibody Titer and Renal Failure Progression in Chronic Antibody-Mediated Rejection

Objective: Chronic renal antibody-mediated rejection (ABMR) is a common cause of allograft failure, but an effective therapy is not available. Extracorporeal photopheresis (ECP) has been proven successful in chronic lung and heart rejection, and graft versus host disease. The aim of this study was to evaluate the effectiveness of ECP in chronic ABMR patients. Patients and Methods: We investigated ECP treatment in 14 patients with biopsy-proven chronic ABMR and stage 2–3 chronic renal failure. The primary aim was to e valuate the eGFR lowering after 1 year of ECP therapy. The ECP responders (R) showed eGFR reduction greater than 20% vs the basal levels. We also evaluated the effectiveness of ECP on proteinuria, anti-HLA antibodies (HLAab), interleukin 6 (IL-6) serum levels, and CD3, CD4, CD8, CD19, NK, Treg and T helper 17 (Th17) circulating cells. Results: Three patients dropped out of the study. The R patients were eight (72.7%) out of the 11 remaining patients. Because ECP was not associated with any adverse reaction, the R patients continued such treatment for up to 3 years, showing a persisting eGFR stabilization. Twenty four hour proteinuria did not increase in the R patients over the follow-up when compared to the non-responder patients (NR). In the R patients, the HLAab levels were reduced and completely cleared in six out of eight patients when compared with the NR patients. The NR HLAab levels also increased after the discontinuation of the ECP. The ECP in the R patients showed a decrease in CD3, CD4, CD8, CD19, and NK circulating cells. The ECP treatment in the R patients also induced Tregs and Th17 cell increases, and a decrease of the IL-6 serum levels. Conclusions: ECP abates the HLAab titer and renal failure progression in patients with chronic renal ABMR, modulating the immune cellular and humoral responses

Stress Echocardiography in Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and >= 40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity (P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001). Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers