WRAPPING OF THE MODERATELY DILATED ASCENDING AORTA BY FRESH AUTOLOGOUS PERICARDIUM

Background and aim of the study. Wrapping of the ascending aorta (AA), isolated or associated with aortoplasty, has never been completely accepted. Some complications, as folding of the aortic wall, compression of the vasa vasorum and changes in the flow pattern, with consequent dilatation of the proximal arch, have been described. We used fresh autologous pericardium (FAP), so far never reported, to wrap the AA, with the aim to stabilize its size when moderately dilated, maintaining the preoperative dimension or limiting the reduction to a few mm. Material and Methods. From 2015 to 2019, 10 patients, who were operated on for valve or coronary surgery or both, underwent wrapping of the AA with FAP. Mean age was 69±7 years and ESII 3.5±1.7. Four patients had moderately impaired ejection fraction (35-49%). Results. There was no early or late mortality. One patient was reoperated on after 48 months for severe mitral regurgitation. At a follow up of 53±14 months, a transthoracic echocardiogram showed that the AA size reduced slightly but significantly, from 45.2±2.0 to 42.5±4.1 mm, p=0.03. The diameter of the proximal arch remained unchanged, from 37.1±1.6 to 36.3±2.9 mm, p=0.20. Conclusions. In presence of moderately dilated AA wrapping can be a reasonable option. The use of FAP stabilizes the size of the aorta after a follow up of 53 months. Maintaining a size similar to the preoperative one avoids the complications related to the procedure.

Efficacy and safety of the second in-hospital dose of tranexamic acid after receiving the prehospital dose: double-blind randomized controlled clinical trial in a level 1 trauma center

Background Prehospital administration of tranexamic acid (TXA) to injured patients is increasing worldwide. However, optimal TXA dose and need of a second infusion on hospital arrival remain undetermined. We investigated the efficacy and safety of the second in-hospital dose of TXA in injured patients receiving 1 g of TXA in the prehospital setting. We hypothesized that a second in-hospital dose of TXA improves survival of trauma patients. Methods A prospective, double-blind, placebo-controlled randomized, clinical trial included adult trauma patients receiving 1 g of TXA in the prehospital settings. Patients were then blindly randomized to Group I (second 1-g TXA) and Group II (placebo) on hospital arrival. The primary outcome was 24-h (early) and 28-day (late) mortality. Secondary outcomes were thromboembolic events, blood transfusions, hospital length of stay (HLOS) and organs failure (MOF). Results A total of 220 patients were enrolled, 110 in each group. The TXA and placebo groups had a similar early [OR 1.000 (0.062–16.192); p = 0.47] and late mortality [OR 0.476 (95% CI 0.157–1.442), p = 0.18].The cause of death (n = 15) was traumatic brain injury (TBI) in 12 patients and MOF in 3 patients. The need for blood transfusions in the first 24 h, number of transfused blood units, HLOS, thromboembolic events and multiorgan failure were comparable in the TXA and placebo groups. In seriously injured patients (injury severity score > 24), the MTP activation was higher in the placebo group (31.3% vs 11.10%, p = 0.13), whereas pulmonary embolism (6.9% vs 2.9%, p = 0.44) and late mortality (27.6% vs 14.3%, p = 0.17) were higher in the TXA group but did not reach statistical significance. Conclusion The second TXA dose did not change the mortality rate, need for blood transfusion, thromboembolic complications, organ failure and HLOS compared to a single prehospital dose and thus its routine administration should be revisited in larger and multicenter studies. Trial registration ClinicalTrials.gov Identifier: NCT03846973.

Two-Year Landmark Survival Analysis after Allogeneic Hematopoietic Cell Transplantation in Acute Lymphoblastic Leukemia: An Analysis from the ALWP of the EBMT

Background Long-term survival and late mortality risk compared to general population for patients (pts) who underwent an allogeneic hematopoietic cell transplant (HCT) is unknown. We analyzed long-term outcomes of 2-year (yr) HCT survivors with acute lymphoblastic leukemia (ALL). Methods Adult pts with ALL who were alive and relapse-free at 2 yrs after first HCT from 2005-2012 were included. We excluded patients who had a cord blood transplant and ex vivo T cell depletion (TCD). Relative survival analysis was used to estimate HCT-related crude mortality taking into account for background population mortality rates of the general population, matched for age, sex, and country in the year of HCT (www.mortality.org). Results A total of 2701 pts were included with a median follow up interval of 99 months and median age of 34 (range 18 - 73.5) yrs. The majority (78.6%) of pts were in 1 st complete remission (CR1) with undetectable MRD (68.3%). There were similar numbers of matched sibling donor (MSD) (43.7%) and unrelated donor transplants (MUD) (53.2%). Most pts received myeloablative conditioning (MAC) (86.5%) and peripheral blood (PB) grafts (75.7%) without in vivo TCD (55.7%). The 10-yr probability for overall survival (OS) and leukemia-free survival (LFS) was 81.3% and 78.2%, respectively. Cumulative incidence of disease relapse and non-relapse mortality (NRM) at 10 years was 9.9% and 11.9%, respectively. The probability of chronic GVHD-relapse-free survival (cGRFS) at 10-yrs was 73.3% (Figure 1). Relapsed ALL and chronic GVHD were common causes of late mortality accounting for 33.9% and 29% of reported deaths, respectively, followed by infection and secondary malignancy. For patients transplanted in countries with available mortality data (92% of patients in our cohort), the probability of dying from another cause is negligible at 1.5% compared to the probability of dying from HCT (16.8%) 10 years after HCT (Figure 1F). Conclusions In a large registry-based study, we showed excellent long-term survival of 81.3% at 10-yr among the 2-yr survivors of HCT for ALL. There was no difference in long term outcomes with respect to conditioning intensity, but utilization of BM graft and in vivo TCD resulted in lower NRM, and better OS. Long-term mortality risk among HCT survivors remains significantly higher than expected for the general age-matched population. Figure 1 Figure 1. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Schroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Bethge: Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Nicholson: Pfizer: Consultancy; BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Peric: Therakos, Servier, MSD, Astellas, Novartis, Abbvie, Pfizer: Honoraria. Dholaria: Janssen: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Jazz: Speakers Bureau; MEI: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; Celgene: Speakers Bureau. Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria.

Trends in Late Mortality and Life Expectancy after Autologous Blood or Marrow Transplantation (BMT) Performed over Three Decades - a BMT Survivor Study (BMTSS) Report

Background: Advances in therapeutic and supportive care strategies have led to increasing use of autologous BMT to ensure durable disease-free survival in patients with hematologic malignancies. However, autologous BMT recipients carry a high burden of morbidity. The cumulative effect of autologous BMT and the long-term morbidity on life expectancy remains unknown. Further, the impact of changes in transplant practice (older age at BMT, increasing proportion of patients undergoing autologous BMT for plasma cell dyscrasias [PCD], increasing use of peripheral blood stem cells [PBSCs] and decreasing use of total body irradiation [TBI]) on late mortality and life expectancy remains unknown. We determined trends in life expectancy and cause-specific late mortality after autologous BMT performed over a 33y period (1981-2014) using the resources offered by BMTSS - a multi-institutional collaborative designed to examine late morbidity and mortality after BMT. Methods: This retrospective cohort included 4,702 individuals who lived ≥2y after autologous BMT performed between 1981 and 2014 at three transplant centers. We examined trends in life expectancy and late mortality over four eras: 1981-1999; 2000-2005; 2006-2010; 2011-2014. Endpoints included all-cause, recurrence-related mortality (RRM) and non-recurrence-related mortality (NRM) and projected reduction in life expectancy. Information on vital status and cause of death was obtained from National Death Index (NDI) Plus program and Accurinct databases. End of follow-up was 04/19/2021. Results: Median age at BMT was 53y (range, 0-78); 58.7% were male, 67.8% non-Hispanic white. Median follow up after BMT was 9y (range, 2-36). PCD was the most common indication for autologous BMT (42.3%). PBSCs were used for 91.6% of the transplants and TBI was used for conditioning in 23.1% of the patients. Across the four eras, the median age at BMT increased (40y→58y), as did the proportion of patients receiving autologous BMT for PCD (13.7%→60.0%) and the proportion of patients receiving PBSCs as the stem cell source (66.6%→99.5%). There was a dramatic decline in the proportion of patients conditioned with TBI (56.4%→5.2%), and those transplanted for acute myeloid leukemia/ myelodysplastic syndrome (AML/MDS) (15.4%→0.2%). Conditional on surviving ≥2y after autologous BMT, patients experienced a 25.8% reduction in life expectancy, representing 7.0y of life lost. In an analysis adjusted for all relevant demographic and clinical predictors and restricted to 5y of follow-up, the years of life lost declined across the four eras from 5y to 1.6y (Fig 1) The adjusted hazard of all-cause mortality also declined over the four eras (reference: 1981-1999; hazard ratio [HR]2000-2005=0.77; 95%CI=0.7-0.9; HR 2006-2010=0.62; 95%CI=0.5-0.7; HR 2011-2014=0.5; 95%CI=0.4-0.6; P trend <0.0001) (Fig 2). Mediation analysis revealed that the reduction in late mortality was evident among those transplanted for Hodgkin lymphoma (HL) or PCD, and among those who did not receive TBI . The 30y cumulative incidence of NRM (29.2%) was higher than that RRM (23.8%) (Fig 3). The adjusted hazard of RRM declined over the four eras (reference: 1981-1999; HR 2011-2014=0.55; 95%CI=0.4-0.7, P trend: <0.0001). Cause-specific late mortality declined for mortality related to infection (P trend <0.0001), subsequent malignant neoplasms (P trend=0.01), cardiovascular disease (P trend=0.001), and renal disease (P trend=0.0002), but not for pulmonary disease (P trend=0.3). Conclusions and Relevance: Late mortality among autologous BMT recipients has declined over a 30y period, likely due to changes in transplant practice (reduction in use of TBI) and improvement in disease-specific therapeutic strategies (newer therapeutic options for PCD and reduction in dose/volume of radiation for HL). Continued efforts need to focus on mitigation strategies for disease recurrence, subsequent neoplasms, infections, and cardiovascular, renal and pulmonary disease in this population. Figure 1 Figure 1. Disclosures Arora: Kadmom: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding. Forman: Allogene: Consultancy; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company. Weisdorf: Incyte: Research Funding; Fate Therapeutics: Research Funding.