Adult Transplant Patients Research Articles

133 - Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplant Patients

133 - Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplant Patients

Fecal microbiota transplantation for treatment of moderate to severe ulcerative colitis: a living systematic review protocol

Background: Several primary studies and systematic reviews (SRs) have been published over the past 10 years to assess the safety and effectiveness of fecal microbiota transplantation (FMT) as a treatment for ulcerative colitis. The objective of this review is to evaluate the efficacy and safety of fecal microbiota transplantation for adult patients with moderate or severe ulcerative colitis. Methods: We will carry out a living systematic review including only randomized controlled trials (RCT) irrespective of publication type, year and language of publication. To prioritize the intervention (TFM administration route), comparisons (placebo, alternative treatment or no treatment) and outcomes (clinical remission, clinical relapse, serious adverse events, clinical response, free time without corticosteroid treatment and health related quality of life) more relevant for supporting the clinical decisions in the treatment of UC patients, we will perform a Delphi process conducted by an expert panel in the field of gastroenterology and colorectal surgery. Searches will be performed in Epistemonikos database and results will be incorporated into the L·OVE platform identified as “Fecal microbiota transplant in ulcerative colitis”. We will evaluate the risk of bias of the included randomized trials using the ROB-2 tool and assess the certainty of evidence using the GRADE approach. We will monitor the L ·OVE platform every two months searching for relevant trials that could imply changes in the available evidence. The living process will end after 12 months of surveillance. PROSPERO registration: CRD42021257579 (29/10/2021).

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults.

Ruxolitinib, a JAK1/2 inhibitor, is used to treat chronic graft versus host disease (cGVHD) in adult allogeneic hematopoietic stem cell transplant patients, but experience in children is limited, perhaps because of lack of pediatric dosing information. In this report, we describe our pediatric and young adult dosing strategy experience in cGVHD. Ruxolitinib was administered orally at 5 mg twice daily for children ≥25 kg or 2.5 mg twice daily if <25 kg. The dose was halved with concurrent azole administration and increased to a maximum of 10 mg twice daily if tolerated. Responses were evaluated using the 2014 NIH consensus criteria. Phosphorylation of lymphocyte STAT5 following dosing, a surrogate of JAK inhibition, was evaluated by flow cytometry. Twenty patients with a median age 14.6 y (range 5-26 y) received ruxolitinib for severe (n = 9) and moderate (n = 11) cGVHD. Median steroid dose was 0.5 mg/kg/d (range 0.08-1.5 mg/kg/d) at ruxolitinib initiation. Two patients with moderate cGVHD achieved a complete response (CR), while 12 patients achieved a partial response (PR) at a median of 48 d (range 17-98 d) from the first ruxolitinib dose, for an overall response rate of 70%. Eleven patients are maintaining their PRs. pSTAT5 on lymphocytes was absent or decreased (0%-6% events) in 5 evaluated patients, suggesting adequate inhibition. Three patients discontinued ruxolitinib because of neutropenia, thrombocytopenia, or elevated alanine aminotransferase. Four patients developed bacterial infections, and 3 experienced symptomatic viral infections. Two patients died from complications related to progressive severe cGVHD. Ruxolitinib using our dosing strategy demonstrates promise for treating cGVHD in children.

Effects of cyclophosphamide related genetic variants on clinical outcomes of adult hematopoietic cell transplant patients.

Genetic variants may influence the pharmacokinetics and pharmacodynamics (PKPD) of cyclophosphamide (CY). CY plays a critical role in conditioning chemotherapy for hematopoietic cell transplantation (HCT), but its use is limited by toxicity. We explored the effect of genetic variants, potentially affecting PKPD of CY, and outcomes after HCT. This observational pharmacogenomic study included 85 adults with hematologic malignancies who received reduced intensity conditioning with CY, fludarabine, and total body irradiation. We collected recipient DNA prior to HCT and evaluated 97 candidate variants in 66 genes and 3 metabolism phenotypes potentially involved in PKPD pathways of CY. In multivariable analysis we investigated the association between the genotypes and four clinical outcomes: Day 180 non-relapse mortality (NRM) and day 180 overall survival (OS), acute graft-versus-host-disease(aGVHD) grades 2-4, and engraftment. p values were not adjusted for multiple testing. The median recipient age was 63years (range 21-75). Acute myeloid leukemia was the most common diagnosis (34%; n = 29). In multivariable analysis adjusted for exposure to phosphoramide mustard, the final active metabolite of CY, we identified 6 variants in 6 genes associated with at least one of theclinical outcomes. An ABCC4 variant (rs9561778) was associated with poor Day 180 NRM (p < 0.01), MUTYH variant (rs3219484) with higher Day 180 NRM and aGVHD (both p < 0.01), and SYNE1 variant (rs4331993) with better Day 180 OS and engraftment (both p ≤ 0.01). The present study suggests that genetic variants influencing the PKPD of CY may help identify patients at risk for inferior outcomes after HCT using CY-based reduced-intensity conditioning.

Extracorporeal membrane oxygenator as a bridge to heart–liver en bloc transplant in a patient with Fontan circulation

Extracorporeal membrane oxygenator as a bridge to heart–liver en bloc transplant in a patient with Fontan circulation

Comparison of endoscopic sinus surgery timing in lung transplant patients with cystic fibrosis

No studies have investigated when endoscopic sinus surgery (ESS) is best performed in lung transplant patients with cystic fibrosis (CF). We sought to examine the effects of ESS timing on pulmonary health in this population. A retrospective review of all adult lung transplant patients with CF who underwent ESS at our academic medical center over a near 25-year period was performed. Patients were split into two groups based on median time from lung transplantation to ESS. Twenty-three patients were included (12 ESS early and 11 ESS delayed). Outcomes included changes in pulmonary function tests (PFTs) from baseline, preoperative to postoperative measurements, the number and duration of hospitalizations for pulmonary exacerbations, and the number of antibiotic courses used specifically to treat pulmonary exacerbations during the 12 months before and after ESS. Baseline demographics, operative history, and pulmonary function characteristics were similar between groups. While the ESS early group saw significant improvement from preoperative percent-predicted FEV1 (ppFEV1 ) at 12months postoperatively (confidence interval [CI]: 0.729-11.452, p=0.030), there were no significant postoperative PFT changes for the ESS delayed group. Postoperative improvement in FEV1 and ppFEV1 at 12months was significantly higher for the ESS early group relative to the ESS delayed group (CI: 0.010-0.583, p=0.043; CI: 1.240-16.692, p=0.025; respectively). The ESS early group had a significant reduction in the need for total antibiotic courses compared with the ESS delayed group (ESS early median: -1, interquartile range [IQR]: -1.5 to -0.5vs. ESS delayed median: 0, IQR: 0 to 0; p=0.027). Earlier ESS interventions following lung transplantation may improve pulmonary function and attenuate pulmonary exacerbations in CF patients.

Using the MDASI-Adolescent for Early Symptom Identification and Mitigation of Symptom Impact on Daily Living in Adolescent and Young Adult Stem Cell Transplant Patients.

Hematopoietic stem cell transplantation (HSCT) requires an intensive pre- and post-procedure course that leads to symptoms including fatigue, nausea/vomiting, and pain, all of which interfere significantly with activities of daily living. These symptoms place a substantial burden on patients during the time period surrounding transplant as well as during long-term recovery. The MD Anderson Symptom Inventory (MDASI) is a symptom-reporting survey that has been successfully used in adult patients with cancer and may have utility in the adolescent and young adult (AYA) population. At the Children’s Cancer Hospital at MD Anderson Cancer Center, we adopted a modified version of the MDASI, the MDASI-adolescent (MDASI-Adol), as a standard of care for clinical practice in assessing the symptom burden of patients in the peri-transplant period. We then conducted a retrospective chart review to describe the clinical utility of implementing this symptom-screening tool in AYA patients admitted to our pediatric stem cell transplant service. Here, we report our findings on the symptom burden experienced by pediatric and AYA patients undergoing stem cell transplantation as reported on the MDASI-Adol. Our study confirmed that the MDASI-Adol was able to identify a high symptom burden related to HSCT in the AYA population and that it can be used to guide symptom-specific interventions prior to transplant and during recovery. Implementing a standard symptom-screening survey proved informative to our clinical practice and could mitigate treatment complications and alleviate symptom burden.

Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis.

Chronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used a machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared with radiologist scoring. This retrospective study included all adult first double lung transplant patients (January 2010-December 2015) with CLAD (censored December 2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus and CLAD phenotype. 88 patients were included (57 bronchiolitis obliterans syndrome (BOS), 20 restrictive allograft syndrome (RAS)/mixed and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (area under the curve (AUC) 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC 0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (hazard ratio 1.23, 95% CI 1.05-1.44; p=0.01). Machine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

Safety and Efficacy of Prophylactic Levofloxacin in Pediatric and Adult Hematopoietic Stem Cell Transplantation Patients

Levofloxacin has been widely used for bacteremia prophylaxis in the pre-engraftment setting for patients undergoing hematopoietic stem cell transplantation (HSCT), but data supporting this practice are inconsistent. In addition to concern for lack of benefit, there are also concerns that this practice could increase the rates of Clostridioidesdifficile (C diff) infections, the incidence of multidrug-resistant organisms (MDRO) or lead to increased incidence of acute graft-versus-host disease (aGVHD) by disrupting the gut microbiome. This study aimed to assess the safety and efficacy of levofloxacin as bacterial prophylaxis in pediatric and young adult patients undergoing allogeneic or autologous HSCT at a single pediatric center. We conducted a retrospective chart review evaluating patients age ≥6 months who underwent HSCT at our center between January 1, 2016, and July 31, 2020. Patients who underwent transplantation before March 2018 did not receive levofloxacin prophylaxis, whereas those who underwent transplantation after April 2018 did receive levofloxacin prophylaxis. Each transplantation was included as a separate episode if the patient underwent more than 1 transplantation during the inclusion time. The primary outcome of this study was the proportion of patients who experienced at least 1 bacterial bloodstream infection (BSI) in the first 100 days post-transplantation. Secondary outcomes included the number of non-levofloxacin antibiotic days post-transplantation, the incidence of aGVHD, the occurrence of C diff infections, and development of MDRO. A total of 370 HSCT recipients with a median age of 6.7 years (range, 0.5 to 39 years) were included in this study. Seventy-two patients had undergone more than 1 transplantation, and thus we had 443 transplantations to observe. Of these, 216 did not include levofloxacin prophylaxis and 227 included levofloxacin prophylaxis. There were no differences in baseline characteristics between the 2 groups except for age; patients in the non-levofloxacin prophylaxis group were younger (8.1 years vs 9.6 years; P=.05). There were no between-group differences in rates of death at 100 days, antibiotic use, fungal infections, or MDRO infections. Patients in the non-prophylaxis group developed more bacterial BSI in the first 100 days post-HSCT (27% versus 17%; P=.004) and more C diff infections (20% versus 9%; P=.003) than patients who received levofloxacin prophylaxis. In addition, more aGVHD was seen in the patients without levofloxacin prophylaxis (P=.014). Levofloxacin prophylaxis given from day -2 of HSCT through engraftment was significantly associated with decreased bacterial BSI in the first 100 days post-transplantation and was not associated with increased risks of C diff, aGVHD, or MDRO. Our study supports the use of levofloxacin prophylaxis in the peritransplantation period. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Risk Factors for Development of Biliary Stricture After Liver Transplant in Adult Patients: A Single-Center Retrospective Study

Identification of risk factors for biliary stricture after liver transplant and its potential prevention is crucial to improve the outcomes and reduce the complications. We retrospectively analyzed donor and recipient characteristics with intraoperative and postoperative parameters to identify the risk factors for development of post-transplant anastomotic and nonanastomotic biliary strictures with additional analysis of the time onset of those strictures. A total of 412 patients were included in this study. Mean (SD) follow-up time was 79 (35) months (range, 1-152 months). Biliary stricture was diagnosed in 84 patients (20.4%). Multivariate analysis indicated that postoperative biliary leakage (odd ratio [OR], 3.94; P=.001), acute cellular rejection (OR, 3.05; P < .001), donor age older than 47.5 years (OR, 2.05; P=.032), preoperative recipient platelet value < 77.5×103/mL (OR, 1.91; P=.023), University of Wisconsin solution (OR, 1.73; P=.041)), recipient male sex (OR, 1.78; P=.072), portal/arterial flow ratio > 4 (OR, 1.76; P=.083), and intraoperative bleeding > 2850 mL (OR, 1.70; P=.053) were independent risk factors for biliary stricture regardless of the time of their appearance. Multiple risk factors for biliary stricture were determined in this study. Some of these risk factors are preventable, and implementation of strategies to eliminate some of those factors should reduce the development of post-transplant biliary stricture.

Stem-Cell Transplantation in Adult Patients with Relapsed/Refractory Hodgkin Lymphoma

Although the majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy, in 85–90% of early stage and 70–80% of advanced-stage disease cases, relapse remains a major problem. Autologous stem-cell transplantation (auto-HCT) after salvage chemotherapy is currently considered to be the standard of care for patients who relapse after first-line chemotherapy or for whom first-line treatment fails. The curative capacity of auto-HCT has been improving with the introduction of new drug-based salvage strategies and consolidation strategies after auto-HCT. Allogeneic stem-cell transplantation (allo-HCT) represents a reasonable treatment option for young patients who relapse or progress after auto-HCT and have chemosensitive disease at the time of transplantation. Allo-HCT is a valid treatment strategy for patients with relapse/refractory HL (r/r HL) because the results have improved over time, mainly with the safe combination of allo-HCT and new drugs. Bearing in mind that outcomes after haploidentical stem-cell transplantation (haplo-HCT) are comparable with those for matched sibling donors and matched unrelated donors, haplo-HCT is now the preferred alternative donor source for patients with r/r HL without a donor or when there is urgency to find a donor if a matched related donor is not present. The development of new drugs such as anti-CD 30 monoclonal antibodies and checkpoint inhibitors (CPI) for relapsed or refractory HL has demonstrated high response rates and durable remissions, and challenged the role and timing of HCT. The treatment of patients with HL who develop disease recurrence or progression after allo-HCT remains a real challenge and an unmet need.

Development and validation of a comorbidity index for predicting survival outcomes after allogeneic stem cell transplantation in adult patients with acute leukemia: a Korean nationwide cohort study.

BackgroundAllogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS).MethodsA Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort. A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort.ResultsIn the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17< score ≤0.4), high-risk (0.4< score ≤0.55), and very high-risk (score >0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P<0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P=0.085 and P=0.018, respectively). Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715.ConclusionThe newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.

Immunologic response of mRNA SARS-CoV-2 vaccination in adolescent kidney transplant recipients.

BackgroundIn the general population, mRNA SARS-CoV-2 vaccines are highly efficacious. Early reports suggest a diminished antibody response in immunosuppressed adult solid organ transplant (SOT) patients, but this has not been reported in pediatrics.MethodsAdolescent kidney transplant recipients (KTR) at our center who received both doses of an mRNA SARS-CoV-2 vaccine had SARS-CoV-2 spike (S) protein antibody presence evaluated 4–8 weeks after their second dose of the vaccine as part of routine clinical care.ResultsThirteen of 25 fully vaccinated patients (52%) had a positive spike antibody. Median age of participants was 19 years old (IQR 18–20) and the median time from transplant was 5 years (IQR 4–9 years). KTR were treated with an immunosuppression regimen including a calcineurin inhibitor, corticosteroid, and antimetabolite (9 with mycophenolate, 3 with azathioprine, and 1 without an antimetabolite due to viremia). Of those who had an antibody response, fewer had a mycophenolate-containing immunosuppressant regimen than non-responders. There was a trend toward better vaccine response and higher anti-S antibody titers at lower doses of mycophenolate. Three patients with prior COVID-19 infection all had a positive antibody response.ConclusionOur results suggest vaccine response in adolescent KRT is lower than that of the general population, but similar to that previously described in adult SOT patients and slightly better than that seen in adult KTR. This data demonstrates vaccination is safe and supports immunizing KTR who remain hesitant. Future studies should focus on better understanding of the cellular immune response to vaccination and strategies to enhance vaccine immunogenicity in pediatric SOT patients.Graphical abstract

Immunosuppressive adherence after kidney transplantation in adult patients treated at an outpatient clinic: a better practice implementation project.

To evaluate the compliance of the practice with the evidence-based criteria in relation to interventions developed to improve the immunosuppressive adherence of adults in postkidney transplantation. A best practice implementation project, based on the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit tool for promoting change in health practice, was conducted. A baseline and a follow-up audit were conducted in a kidney transplant clinic, including a sample of kidney transplant patients with a maximum of 30 days postoperatively, and health professionals working in the post-transplant period. The basic audit revealed that the parameters related to the professionals' knowledge did not reach adequate compliance; the involvement of patients in strategies to overcome barriers that interfere with nonadherence; guidelines for specific therapeutic regimens for patients and the prescription of immunosuppressants according to the patient's routine. To solve the identified weaknesses, training strategies were implemented with the professionals, follow-up by telephone contact with the patients and the elaboration and distribution of an educational booklet with guidance on the use of immunosuppressants, leading to an increase from 50 to 87.5% of conformity in the evaluated service. The evidence implementation project provided improvements in clinical practice behaviors. It demonstrated that there are strategies that facilitate the implementation of evidence regarding the promotion of interventions to improve immunosuppressive adherence. Additional audits are still needed to improve and assess the quality of interventions promoted by professionals regarding drug adherence in the post-transplant period, as well as to verify the behavior of patients, ensuring that the project will be maintained and supported.

Lung transplant recipient attitudes and beliefs on accepting an organ that is positive for hepatitis C virus.

Little is known about patient perceptions regarding HCV+ organ use in non-HCV-infected recipients. This study examined factors influencing the decision to accept HCV+ organs and the resulting impacts. Adult lung transplant (LT) patients or candidates who had consented to receive an HCV+ organ completed a survey including multiple choice, a five-point Likert scale, and free-text answers. A total of 67 LT recipients or candidates who had consented to receive HCV+ organs were enrolled, of which 21/67 (31%) received HCV+ lungs, 39 (58%) HCV- lungs, and seven (10%) were still waiting. Pre-transplant, 50/67 (75%) patients felt it was either "completely safe" or "very safe" to accept an HCV+ organ. Although 22/67 (33%) said they never or rarely took risks, they still made the decision to accept an HCV+ organ. Common reported reasons were desperation, perception of having "no choice," and increasing symptom severity. In the subset of patients that were transplanted with an HCV+ organ (n=21), only 12.5% reported second thoughts about accepting. Post-transplant, the majority (87.5%) never felt any anxiety about HCV and most (83%) reported no impact from HCV. Perception of treatment tolerability and ease was highly favorable. Use of HCV+ organs demonstrated minimal detrimental perceived impacts on lung transplant patients. Patients generally found the experience to be very positive.

Stable Engraftment with Haploidentical Peripheral Blood Stem Cell Transplantation in Adult Patients with Sickle Cell Disease

The widespread application of allogeneic hematopoietic stem cell transplantation (HSCT) to cure patients with clinically aggressive sickle cell disease (SCD) has been limited by a lack of HLA-matched sibling donors. HSCT from a haploidentical donor represents a feasible option to increase transplant availability to a majority of the patients. However, current published studies using haploidentical donors in adults with SCD have resulted in long-term event-free survival rates of only 50-57%.Here we describe 10 consecutive haploidentical HSCT (haplo-HSCT) performed in adult patients with clinically aggressive SCD lacking an HLA-matched sibling donor. The median age of recipients was 27 years (range, 20-52 years) and all 10 patients met at least two standard SCD eligibility criteria for HSCT (Table 1). Based on our successful experience in matched related peripheral blood stem cell (PBSC) HSCT using a nonmyeloablative conditioning regimen with alemtuzumab 1mg/kg and 3 Gy total body irradiation (TBI), we initially performed two haplo-HSCT using the same conditioning regimen followed by high dose post-transplant cyclophosphamide (PT-Cy) at 50mg/kg on day+3 and +4. Both SCD patients failed to engraft donor cells and recovered autologous neutrophils on day +39 and day +34, respectively.In the following 8 patients, transplanted between September 2015 and March 2017, we utilized a modified version of the Hopkins protocol with: fludarabine 30mg/m2, Cy 14.5mg/kg, 3 Gy TBI (increased from the original 2 Gy dose), antithymocyte globulin 0.5mg/kg, PT-Cy 50mg/kg, and infusing mobilized PBSC instead of marrow cells (Table 1). G-CSF at 5µg/kg was administered starting on day +12 post-HSCT in neutropenic patients with HbS <30% and the median time to neutrophil engraftment was 22 days (range, 18-23 days). All 8 patients initially engrafted donor cells and only 1 (12%) subsequently developed secondary graft failure. The remaining 7 (88%) currently maintain a stable donor cell engraftment. Transplant related toxicities included: neutropenic fever resolving after antibiotic therapy (n=8/8), ≥ grade II mucositis (n=3/8), CMV reactivation (n=2/8), and small intracranial hemorrhages (n=2/8) on (i) day +10 in a patient refractory to platelet transfusions that resolved after cross-matched platelets became available, and, (ii) on day +12 in a patient with prior stroke history that resolved after increasing the platelet threshold from 50 to 100 x103/µL. Acute GVHD ≥ grade 2 was seen in 2/8 patients (one non-compliant with immunosuppressive treatment), with complete resolution after steroid therapy in one case, and transformation into chronic GVHD (skin, eye and liver) in the other. No other cases of chronic GVHD have been observed to date. With a median follow up of 9 months (range, 5-22 months), all 8 patients are alive and 7 (88%) maintain >90% donor cell chimerism with an improved median hemoglobin concentration from 8.8g/dL (range, 6.4-12.8g/dL) to 13.3g/dL (range, 9.9-15.3g/dL).Our study demonstrates that modifying the Hopkins conditioning regimen by increasing the TBI dose from 2Gy to 3Gy and using PBSC instead of bone marrow grafts allows 88% of SCD patients to achieve stable donor engraftment without severe toxicity. We also demonstrate that G-CSF can be safely administered to adult patients with SCD after HSCT. Haploidentical HSCT is the only curative option for many adult patients with clinically advanced SCD and our study suggests a basis for larger, multicenter clinical studies. [Display omitted] DisclosuresPatel:Celgene: Consultancy, Honoraria. Khan:Takeda: Research Funding; Gilead: Consultancy; Teva: Speakers Bureau. Gordeuk:Emmaus Life Sciences: Consultancy.

A retrospective analysis of the safety and efficacy of apixaban use after lung transplant.

Direct acting oral anticoagulants (DOACs) have become the mainstay of treatment for patients requiring anticoagulation for atrial arrhythmias and venous thromboembolism (VTE) but safety and efficacy has not been established in lung transplantation. This is a retrospective review of 28 adult lung transplant patients who were prescribed apixaban for stroke prevention in atrial arrhythmias or treatment of VTE between October 15, 2015 and December 31, 2018. The primary outcome was a composite of efficacy and safety measured by recurrence or breakthrough of stroke or thromboembolism and bleeding events. Seven patients were treated for atrial arrhythmias and 21 treated for VTE. Fifteen patients received CYP3A4 or P-gp inhibitors at initiation of anticoagulation, and 4 of these patients received strong CYP3A4 inhibitors. During the follow-up period, one breakthrough DVT and one clinically relevant non-major bleed were observed. These data suggest that apixaban may be safe to use for lung transplant patients, and larger studies are warranted to assess long-term outcomes as well as safety and efficacy of alternative DOACs.

Torque Teno Virus Does Not Predict Cytomegalovirus Infection Post-Lung Transplantation

Purpose Torque teno virus (TTV) is a highly prevalent, non-pathogenic DNA virus that has been shown to correlate with immunosuppression post-transplantation. Cytomegalovirus (CMV) is the most common opportunistic infection to occur post-lung transplantation and is associated with morbidity and mortality. We evaluated the association between plasma TTV load and subsequent occurrence of CMV infection in lung transplant recipients at moderate risk for a CMV infection. Methods All adult, first-time lung and heart-lung transplant patients with moderate risk serotype for CMV infection [donor positive (D+) / recipient positive (R+)] transplanted between September 2005 and December 2013 in our program were included in the study. During this period, our program's CMV prophylaxis strategy was to use valganciclovir for 3 months post-transplant. Existing stored blood samples were retrieved and TTV DNA was quantified using real-time polymerase chain reaction (PCR), measured at 3, 4 and 5 months after lung transplantation, as well as at the time of detection in those who developed a CMV infection. Paired t-tests were used for serial data comparisons and Cox regression was performed to determine an association between log TTV PCR levels and CMV infection within 6 months of discontinuing antiviral prophylaxis. Results During the study period 297 patients were transplanted. Of these patients, 89 patients had D+/R+ serostatus, of which blood samples for TTV PCR testing were available for 76 patients. Only 1 patient did not have any detectable TTV PCR post-transplant. Within this cohort, 34/75 patients (45%) developed a CMV infection within 6 months of discontinuing antiviral prophylaxis. Baseline mean log TTV PCR levels one week after discontinuation of CMV prophylaxis was no different between those that went on to develop a CMV infection and those that did not (6.80 ± 1.08 vs 7.08 ± 0.75, p=0.20). For those developing CMV infection, mean log TTV PCR levels were slightly lower at the time of CMV infection compared to baseline levels (6.45 ± 1.36 vs 6.98 ± 0.72, p=0.04). TTV viral load was not associated with time to CMV infection, HR 0.76 (95% CI 0.55 - 1.05, p=0.09). Conclusion TTV PCR levels at the time of discontinuation of CMV prophylaxis in CMV D+/R+ lung transplant recipients were not associated with subsequent CMV infection. TTV's role in predicting future infection requires further study.

Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified.

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10594 articles. After exclusion, 22 studies (n=75799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR=1.43, 95% CI=1.09-1.89, P=0.01), 1-year (OR=1.46, 95% CI=1.08-1.97, P=0.01), and 3-year (OR=1.37, 95% CI=1.01-1.84, P=0.04) graft survival. WL grafts were less associated with retransplantation (OR=0.57; 95% CI=0.41-0.80; P<0.01), vascular complications (OR=0.53, 95% CI=0.38-0.74, P<0.01) and biliary complications (OR=0.67; 95% CI=0.47-0.95; P=0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.

32 - Non T–Cell Depleted Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

32 - Non T–Cell Depleted Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation