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.

Normal Life Expectancy for Polycythemia Vera Patients Is Possible

Introduction: Polycythemia vera (PV), a chronic myeloproliferative neoplasm, is characterized by shortened overall survival (OS) due to potentially fatal thrombosis, progression to myelofibrosis (MF), and acute leukemia. Treatment with aspirin, attentive phlebotomy (PHL) and cytoreductive agents can prevent thrombosis; but it is unknown whether available treatments can achieve a normal life-span for PV patients (pts). Our objective was to assess the extent by which PV alters OS of pts receiving available treatment at our center and in the community. Methods: We obtained demographics and survival data of adult PV pts from our Weill Cornell Medicine (WCM) Research Database Repository (PV-WCM) diagnosed from 1974-2020 as previously described (Abu-Zeinah et al. Leukemia 2021); and from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, 2001-2017. PV-WCM thrombosis and MF progression data were available. WCM institutional review board approval and SEER data use agreement were in place. OS of PV pts was estimated using Kaplan-Meier (KM) analysis. Propensity Score Matching was used to identify a subgroup of SEER pts (PV-SEER) with similar age, sex, and race demographics to PV-WCM for comparison of OS. Cox proportional hazards was used for multivariable analysis (MVA) of survival. Actuarial survival of the US population matched by age, sex, race, and year-of-birth was obtained from US Census. Observed OS was compared to actuarial OS using one-sided log-rank test. Results: We identified 470 PV-WCM and 16,492 PV pts from SEER. The median OS of the PV-WCM cohort and the SEER population was 26.6 and 12.8 years, respectively, but the groups differed by age and sex (Fig 1A). PV-WCM and matched PV-SEER, however, were well balanced by age, sex, and race (standardized mean difference <0.1). The median OS of PV-WCM was 10.8 years longer than PV-SEER (p<0.001, Fig 1B). MVA confirmed 65% lower mortality in the PV-WCM group relative to the PV-SEER population (p<0.001, Fig 1C). PV-SEER OS was shorter than actuarial OS of the US population (mortality HR 2.47, p<0.001), whereas PV-WCM OS was not significantly different than expected (mortality HR 1.15, p=0.136). Excess late mortality was observed in PV-WCM after 17 years, potentially due to increased incidence of MF progression, affecting almost 50% of PV pts after 25 years (Fig 1D). Discussion: These data point to the success of attentive management with aspirin, targeted PHL, and cytoreductive therapy at a specialty center in reducing the mortality of PV, owing in part, to ELN and NCCN treatment recommendations for preventing fatal thrombosis. Although excess thrombosis was not eliminated in PV-WCM pts, the incidence rate was low after the first two years (Fig 1D). In contrast, the incidence of MF progression increased, potentially contributing to excess late mortality. Current PV risk stratification and treatment recommendations neither predict nor aim to mitigate progression to MF, and do not satisfy the needs of younger, low-risk pts who are often symptomatic and harbor a lifetime threat of progression (Fig 1E). The recent Low-PV study showed that low-risk pts may also benefit from cytoreductive therapy with an agent such as interferon-alpha (rIFNα) over PHL alone (Barbui et al. Lancet Hematol 2021). PV-WCM pts treated with rIFNα (n=137), previously shown to have improved MF-free survival and OS (Abu-Zeinah et al. Leukemia 2021), had an OS similar to the matched US population (p=0.33, Fig 1F); whereas pts not treated with rIFNα had modestly shortened OS (HR 1.26, p=0.03). Because PV progression is among the leading causes of late morbidity and mortality, and available therapy can mitigate this, it may be time to reconsider and improve upon PV risk stratification and treatment. Conclusion: This large population-based and single center study shows that although PV survival remains shortened, normal life expectancy for PV pts is possible with available care. The discrepancy between survival in the community and at a specialized center highlights the need for greater community outreach, health equity, and education regarding treatment standards for PV. Hopefully, this study motivates development of new PV risk stratification and treatment recommendations that focus not only on hematologic control and thrombosis prevention, but also on preventing MF progression, improving OS, and restoring normal life expectancy. Figure 1 Figure 1. Disclosures Abu-Zeinah: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Silver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees ; MPN-RF (Foundation): Research Funding; Constellation: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Interferon-alpha is used off label in the treatment of polycythemia vera.