Transplant Unit Research Articles

Long-Term Persistence of Mixed Full Donor Chimerism after Double Cord Blood Transplantation. Example of Tolerance in Allogeneic Hematopoietic Cell Transplantation Setting

Background Double umbilical cord blood transplantation (UCBT) is recognized as an alternative source of hematopoietic donor cells for allogeneic haematopoietic cell transplantation (HCT), particularly in adult setting. Because of important infectious complications, UCBT are rarely utilized and more and more replaced by haplo-identical cell transplantation for adult patients. Nevertheless, some very good results were observed with a long-term follow-up. In most cases, after several weeks, one unit turns immuno-dominant and thus, the second one is no longer detected. Patients and Methods We reported three cases of long-term mixed full donor chimerism associated to documented complete remission of haematological malignancies after double UCBT. The indications of UCBT were acute myeloid leukaemia for 2 patients [1 AML MRC (female of 65 years) and 1 transformation of Fanconi disease (female of 20 years)] and acute lymphoid leukaemia for 1 patient (female of 22 years). AML received a reduced intensity and ALL a standard conditioning. The general characteristics of recipients and UCB are presented in Table 1. The chimerism follow-up were performed by STR and qPCR techniques with a sensitivity of 5 and 0.2% respectively. Early after transplantation, patient 1 developed a grade I graft-versus-host disease (GVHD), patient 3 a grade II GVHD treated by extracorporeal photopheresis, and patient 2 did not develop any GVHD. The follow-up of these patients were 14, 13 and 8 years respectively after UCBT without any episodes of relapse and at the last follow-up still a total donor mixed chimerism. Results Results of STR and qPCR after transplantation early revealed the presence of the two transplant units with a total donor chimerism (Table 1). Patient 1 presented a perfectly balanced chimerism with 54 % of the majority unit. The other two patients showed an imbalance in the proportions of their two UCB with 83% and 72% of their majority units respectively but a long-term persistence of 17% and 28% of their second UCB. The study of total blood chimerism during their follow-up revealed a stabilization of the proportions of the two units during the first year (Figure 1). A more in-depth study of circulating cell subsets (CD3+, CD15+ and CD19+) chimerism of patient 1 revealed a very strong initial imbalance of the two units, which ended up being balanced at two years after transplantation. In the other two patients, the respective study of CD3+ and CD33+ cells showed a stabilization of the two unit percentage around six months after transplantation. At five years after transplantation, patient 1 had an in-depth study of circulating cells sub-populations (CD4+ T lymphocytes, CD8+ T lymphocytes, B-lymphocytes, natural killer cells, regulatory T cells, monocytes, naive CD4+ and CD8+ T lymphocytes) by flow cytometry, after separation of the two units cells by specific monoclonal antibody directed against HLA mismatching antigen (HLA-A2). This analysis revealed an imbalance in the percentage of NK and monocytes. The immune-dominant unit had three times more NK cells than the other one and this imbalance ratio increased by twenty-two for monocytes. A co-culture study of the CD4+ lymphocytes demonstrated a lack of reactivity of both unit against the other one but a normal ability to react against an allogeneic third-part cell. Conclusions This expected tolerance, highlighted in co-culture experience, showed rare cases of naturally induced graft tolerance. A study of tolerance markers and underlying mechanisms in these special cases of persistent mixed full donor chimerism is necessary to acquire better knowledge and to define more investigations ways for the induction of tolerance in patients receiving hematopoietic cell transplantation or organ transplantations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Feasibility and Efficacy of Romiplostim for the Treatment of Persistent Thrombocytopenia after Allogeneic Stem Cell Transplantation. a Single Centre Experience

Introduction. Persistent thrombocytopenia (PT) due to delayed primary platelet recovery or secondary graft failure with prolonged thrombocytopenia is a relevant and relatively common complication after allogeneic stem cell transplantation (alloSCT). It can result in transfusion dependence and hemorrhagic events, leading to increase of morbidity and mortality. Concomitant causes of PT after alloSCT are several and can include viral infections, graft-versus-host disease (GvHD), drug toxicity, thrombotic microangiopathy (TMA) and immune thrombocytopenia (ITP). Together with the treatment of the primary cause and the support with platelet transfusion, the use of thrombopoietin receptor agonists (TPO-RAs), which proved to be effective in several scenarios (e.g. ITP or aplastic anemia), is gaining a fundamental role also in the post alloSCT setting. To date, the use of TPO-RAs after transplant has been investigated in small studies or case reports. In this study, we evaluated the use of romiplostim in a larger patient cohort to determine its safety, efficacy and potential predictors of response. Materials and methods. We conducted a retrospective study on consecutive patients undergoing alloSCT and receiving romiplostim for the treatment of PT at the bone marrow transplantation unit of the University Hospital of Ulm. PT was defined as a platelet count < 20 Giga/l for 7 consecutive days after engraftment, the need for continuous transfusion during the post-transplant follow-up or a not rapidly reversible decrease of >50% of the platelet count not due to relapse of underlying hematological disease. Response to treatment was defined as a platelet count >50 Giga/l for at least 7 consecutive days without transfusion. Patients with residual bone marrow involvement of primary hematological disease were excluded. Univariate analysis was conducted using Fisher's exact test or Mann-Whitney-U-test. Results. Between 01/2019 and 12/2021 we identified a total of 119 out of 255 transplanted patients (46,7%) with PT receiving, as a part of the treatment, romiplostim during the post-transplant follow-up. Patient characteristics are listed in Table 1. The median platelet count at baseline was 32 Giga/l (r = 0 - 88). We started with romiplostim 250μg on a weekly basis, in 46,2% of cases the dose was escalated to 500 µg during treatment. Seventy-three percent showed a clinical response to treatment with a median time to response of 40 days (r = 7 - 565). We observed adverse events like thrombosis, pain syndrome, dizziness in only 8,4% of patients. The median duration of treatment was 168 days (r = 18 - 761). In patients with response, the median platelet count was 91 Giga/l (r = 53 - 212). In univariate analysis, we evaluated potential risk factors associated with poor response to romiplostim. While the presence of a viral reactivation (like CMV, EBV, BKV, HSV1) requiring systemic treatment was associated with a significant lower response rate (47.6% versus 79.6%, respectively for patients with or without reactivation, p= 0.005), the presence of active GvHD (also in case of steroid-refractory (SR) forms), of TMA and the number of CD34-positive stem cells of the graft did not play a role in determining the efficacy of romiplostim. We also evaluated the influence of graft cryopreservation, which was performed increasingly during the SARS-CoV-2 pandemic, on the rate of efficacy of romiplostim in PT treatment. We could not identify a significant difference as compared to the non-cryopreserved grafts. Conclusion. Our results indicate that romiplostim is overall well tolerated and represents a reasonable and effective treatment for PT after alloSCT. We observed that viral infections requiring systemic antiviral treatment could represent a predictor of worse response, which could potentially be explained by the myelotoxicity induced not only by the virus itself but also as a consequence of antiviral substances. Of note, especially considering that SR GvHD or TMA did not seem to impair the efficacy of romiplostim, the stimulation of TPO receptor could play a role in reducing the rate of morbidity and mortality associated with such severe complications of the post transplant follow-up. Also, cryopreservation did not impact on the rate of success of TPO-RAs based treatment strategy. These preliminary results need to be further validated in larger and prospective cohorts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Training and Validation Cohorts for Predicting the Impact of High Molecular Risk Mutations after Allogeneic Stem Cell Transplantation in Myelofibrosis

Introduction Myelofibrosis (MF) is the most aggressive form of Philadelphia negative myeloproliferative neoplasm and allogeneic hematopoietic stem cell transplantation (HSTC) is the only curative approach, but non relapse mortality limits the indication for HSTC to high-risk patients. The prognostic evaluation of MF patients is evolving during time together with a better understanding of the mutational landscape of this disease. The presence of high molecular risk (HMR) mutations, specifically ASXL1, SRSF2, EZH2, IDH1, IDH2 and U2AF1Q157, harbors a detrimental effect on survival and leukemic transformation and has been incorporated in different prognostic scoring systems. In this multicenter study we aimed to determine the impact of HMR mutations on transplant outcome. Methods We studied two independent cohorts of patients: 44 patients (training, retrospective cohort) were part of a multicenter, randomized GITMO (Gruppo Italiano Trapianti di Midollo Osseo) clinical trial (Patriarca F, BBMT 2019) and 29 patients (validation, prospective cohort) were subsequently recruited at the Bergamo Bone Marrow Transplant Unit. Patients from the training cohort (median age 56, range 36-66) were conditioned with busulfan-fludarabine or thiotepa-fludarabin while patients in the validation cohort (median age 61, range 36-67) were conditioned with a reduced intensity thiotepa-busulfan-fludarabin regimen. The mutational profile obtained on the pre-transplant DNA was performed by sequencing 30 myeloid related genes by applying SOPHia GENETICS Myeloid Solution on Illumina MiniSeq platform. Results In the training retrospective cohort, driver mutations were detected in 40 (29 JAK2/8 CALR/3 MPL) patients, with 4 patients having a triple negative MF. At least one HMR mutation was detected in 43% of patients and an unfavorable karyotype was present in 18% of patients. According to the Mutation-Enhanced International Prognostic Scoring System 70 plus (MIPPS70+) scoring system, 77% of patients were allocated in the high/very high groups. With a median follow up of 4.2 years (range 0.02-9), the 5-years Overall Survival (OS) and Progression Free Survival (PFS) were 61% and 45% respectively. The 5-years Non-Relapse Mortality (NRM) and Cumulative Incidence of Relapse (CIR) were 25% and 30%. In the prospective validation cohort, a driver mutation was detected in all patients (15 JAK2/7 CALR/7MPL). At least one HMR mutation was detected in 48% of patients and an unfavorable karyotype was present in 24% of patients. Patients allocated to the MIPPS70+ high/very group were 52%. After a median follow up of 10.7 months (range 0-44), the 2-years OS and PFS were 61% and 49% respectively. The 2-years NRM and CIR were 33% and 18%. In the training cohort, a higher risk of death and progression was observed in patients with high/very high risk MIPPS70+ prognostic index [HR for OS 4.3 (95% CI 0.6-33.1), HR for PFS 4.1 (95% CI 0.9-16.9)]. Conversely, the presence of HMR mutations did not significantly affect OS, PFS (Figure 1), NRM or CIR. The prognostic significance of MIPSS70+ risk classification was confirmed in the validation cohort, with a higher risk of death and progression for high/very high MIPSS70+ group [OS HR 3.2 (95% CI 0.4-27.1), PFS HR 3.8 (95% CI 0.5-31.4)]. Similarly, in the validation cohort the presence of HMR mutations did not affect transplant outcome, with no impact on OS, PFS (Figure 2), NRM or CIR. In the whole group of 73 patients, the presence of JAK2V617F mutation showed an adverse prognostic impact on CIR [HR 3.4 (95% CI 1-11.8)], while MIPPS70+ confirmed its role on PFS. Conclusions In this study we prospectively confirmed that the presence of HMR mutations did not impact on transplant outcome. Allogeneic stem cell transplantation can lead to a significant cure rate of MF patients, regardless the presence of HMR mutations. Patients in the high/very high MIPSS70+ risk group had a higher risk of death and progression after transplant. Appropriate timing and selection of patients is crucial for transplant outcome in MF. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Burnout, mental health symptoms, and empathy in healthcare workers who care for children treated in a liver transplant center.

The healthcare workers in pediatric liver transplantation units are exposed to various stresses; however, their burnout has not been clarified yet. This study aimed to determine burnout, psychological symptoms and empathy levels in healthcare workers, to examine the relationship between these variables and to investigate the predictors of burnout. This cross-sectional study was conducted on healthcare workers in Turgut Özal Medical Center Pediatric Liver Transplant Institute. The participants filled out a questionnaire that investigating demographic and occupational characteristics, and including questions from Toronto Empathy Questionnaire, Maslach Burnout Inventory, and Brief Symptom Inventory. Fifty healthcare workers participated in the study. Based on moderate and higher severity scores, 48% of the participants were emotionally exhausted, 22% of them were depersonalized. All of them had a high perception of personal accomplishment. There was a correlation between psychological symptoms level and emotional exhaustion and personal accomplishment as well as empathy and personal accomplishment. Not choosing the profession and the department willingly, age, education level, marital status, duration of profession, unit, not receiving in-service training, empathy, depressive symptoms and hostility scores predicted different aspects of burnout. Considering that burnout and psychological stress lead to reduced professional abilities and the development of serious complications, the results obtained can guide managers on the measures to be taken.

Vancomycin-resistant Enterococcus outbreak in a pre- and post-cardiothoracic transplant population: Impact of discontinuing multidrug-resistant organism surveillance during the coronavirus disease 2019 pandemic.

Many institutions suspended surveillance and contact precautions for multidrug-resistant organisms (MDROs) at the outset of the coronavirus disease 2019 (COVID-19) pandemic due to a lack of resources. Once our institution reinstated surveillance in September 2020, a vancomycin-resistant Enterococcus (VRE) faecium outbreak was detected in the cardiothoracic transplant units, a population in which we had not previously detected outbreaks. An outbreak investigation was conducted using pulsed-field gel electrophoresis for strain typing and electronic medical record review to determine the clinical characteristics of involved patients. The infection prevention (IP) team convened a multidisciplinary process improvement team comprised of IP, cardiothoracic transplant nursing and medical leadership, environmental services, and the microbiology laboratory. Between December 2020 and March 2021, the outbreak involved thirteen patients in the cardiothoracic transplant units, four index cases, and nine transmissions. Of the 13, seven (54%) were on the transplant service, including heart and lung transplant recipients, patients with ventricular assist devices, and a patient on extracorporeal membrane oxygenation as a bridge to lung transplantation. Four of 13 (31%) developed a clinical infection. Cardiothoracic surgery/transplant patients may have a similar risk for VRE-associated morbidity as abdominal solid organ transplant and stem cell transplant patients, highlighting the need for aggressive outbreak management when VRE transmission is detected. Our experience demonstrates an unintended consequence of discontinuing MDRO surveillance in this population and highlights a need for education, monitoring, and reinforcement of foundational infection prevention measures to ensure optimal outcomes.

Intraoperative portal vein stenting through umbilical vein approach: An innovative salvage procedure for portal vein thrombosis in pediatric liver transplant.

IPVS is considered a last resort or a salvage procedure in the event of recurrent PV thrombosis despite multiple attempts at redo PV anastomosis. We employed the opened umbilical vein approach to place the stent in the PV and deliver anticoagulation through a catheter. From Jan 2017 to Feb 2022, 150 patients underwent pediatric transplantation at department of liver transplant and hepatobiliary surgery unit, Indraprastha Apollo hospitals, New Delhi. Age, weight, PELD Score, diagnosis, portal vein diameter on preoperative CT, Portal flow after stenting, decrease in spleen size after stenting in follow-up CT were collected from a prospectively maintained data base and reviewed. Eight patients underwent IPVS following LDLT (mean age-10.6 ± 2.2 months, mean weight 8.1 ± 1.6, mean PELD score 32.7 ± 7.3). The mean PV diameter on preoperative CT scan was 3.6 mm (range 2.7-5.6 mm). The mean portal flow following stenting was 718.75 cc/min. Percentage reduction in size of the spleen was 26.35% beyond 2nd post-operative week. No patient had recurrent PV thrombosis following IPVS and all maintained an adequate portal flow throughout the immediate postoperative period. Two patients had in-hospital mortality secondary to septic complications. Umbilical vein approach is technically feasible, easy to manipulate the stent and catheter placement after stenting helps to deliver anticoagulants locally.

Hepatitis B sero-prevalence among hematology patients: importance of Anti-HbcAb and efficiency of antiviral prophylaxis.

Hepatitis B infection is an important problem in immune suppressed patients. Anti HbcAb is an important marker that shows past exposure to virus. In this study, we retrospectively searched HBV serology among the patients who had Bone Marrow Transplantation (BMT) or chemotherapies (CT) at Medicalpark Izmir Hospital Bone Marrow Transplantation Unit; changes in viral parameters throughout therapy; and tried to find the efficiency of antiviral prophylaxis. We retrospectively evaluated the viral parameters; HbsAg, Anti HbsAb, Anti Hbc IgG, HbeAg, Anti Hbe Ab, HBV DNA, HCV RNA which were carried out before BMT and CT. We grouped the patients as latent HBV infection and inactive carriers. Started antiviral treatment as prophylaxis, monitored the changes in serological parameters and defined HBV related situations. A total of 584 patients were evaluated retrospectively. Twenty patients were having latent HBV infection. Ten patients were inactive carriers of HBV. In post-transplant period, the patients were screened for 11 months (1-38 months). None of the patients experienced HBV activation during follow period. The best approach in HbcAb positive patients with planned immunosuppressive treatment is the use of anti-viral agents before immune suppression and close monitoring of the patients HBV-related markers.

Effect of COVID-19 Pandemic on Hematopoietic Stem Cell Transplant Activity: Experience of a JACIE-Accredited Center.

The adoption of international quality and accreditation standards is important for the success of transplant centers. Guidelines from the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE) have enabled quality management of the operations of clinical units of cellular therapy centers, including cell collection and processing, thus minimizing errors and adverse events. COVID-19 has had significant implications for immunocompromised patients, particularly hematopoietic stem cell transplant recipients, as well as their donors and caregivers. Here, we retrospectively examined measures, taken in our transplant center in Turkey during the pandemic period between March 2020 and October 2021, to investigate how JACIE accreditation has affected patient, donor, product, and employee safety. We analyzed data on transplant activity, as well as donor, patient, product, and employee safety, during the pandemic in 3 separate 6- month periods. The measures were analyzed starting from March 2020, when the first COVID-19 case was seen in Turkey. Since the beginning of the pandemic, 140 patients have undergone stem cell transplant in our center. Stem cell transplant was delayed in 22 patients because of the pandemic. Transplant was also postponed due to COVID-19 positivity in 6 patients, and 2 patients died due to COVID-19 infection during the transplant process. Unrelated donor activity continued to be performed safely throughout this period. COVID- 19 infection developed in 12 of the 52 personnel working in the bone marrow transplant unit, one of whom needed intensive care due to severe pneumonia. In terms of quality management activities, the impact of the pandemic was greatest during the first month. Results from our retrospective study examining the impact of JACIE accreditation in a stem cell transplant center during the COVID-19 pandemic showed that, when national and international guidelines are followed, JACIE accreditation can facilitate adaptation to changing conditions in transplant centers.

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases.

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

Surgery of the Soul: Reflections on a Curious Career

Surgery of the Soul: Reflections on a Curious Career

Current state of antimicrobial stewardship and organ transplantation in Thailand.

Antimicrobial stewardship (AMS) is a coherent set of actions to optimize antimicrobial use, improve patient outcomes, and reduce antimicrobial resistance (AMR). Thailand's national strategic plan has included AMS since 2017. Due to an increased risk of infection and AMR, solid organ transplant (SOT) recipients can benefit from antimicrobial stewardship programs (ASPs). However, the AMS in SOT has not been well defined. Balancing ASPs with the need for early and frequent antimicrobial treatment in this population is challenging. This review assesses the barriers and potential strategies of AMS in SOT in the setting of Thailand. We used PubMed to identify published articles on AMS in organ transplantation in Thailand from January 2013 to January 2022. We also searched local literature and local data from Google Scholar and Google. Finally, we described the AMS experience at Ramathibodi hospital as a proxy for transplant centers in Thailand. There was no specific article on AMS in SOT in Thailand. At our hospital, ASPs have been part of the hospital's routine patient care, including the practice in the transplant unit. Modifiable challenges to AMS in SOT include prescriber opposition, diagnosis uncertainty, and lack of high quality. Both systems and individualized approaches should be implemented to overcome these barriers. The potential interventions include shortening antibiotic time-out, updating clinical guidelines, continuing education, handshake ASP, adopting new technology, and further research. There are limited data on AMS in organ transplantation in Thailand. Strategic priorities should focus on modifiable barriers tailored to organ transplantation. Quality improvement should be ensured by process and outcome measures.

ABCL-175 Bilharzial Colitis Post-Autologous Stem Cell Transplantation in Non-Hodgkin Lymphoma Patient: A Case Report

Autologous hematopoietic stem cell transplantation (ASCT) is considered the standard of care in relapsed/refractory lymphoid malignancies. One major complication is the occurrence of infection, which is directly related to high doses of chemotherapy and the consequent major immunosuppression, breach of the mucous membrane barrier in the gastrointestinal tract, and line-related infections. The most common infection in post-transplant is bacterial, fungal or viral in nature. A case of bilharzial colitis post-ASCT for R/R diffuse large B cell lymphoma (DLBCL). A case report from March 2018 till now. Hematology and transplant unit, Oncology Center, Mansoura University, Egypt. A 22-year-old male patient diagnosed as R/R DLBCL, stage IIIs, high-intermediate risk IPI. The patient was in overall good condition (ECOG performance status 0) and HCT-CI: 0 points. He received high-dose bendamustine/etoposide/cytarabine/melphalan chemotherapy and ASCT, a total of 8×106/kg bodyweight CD34+ stem cells were administered on Day 0. ASCT procedure was complicated by left lower limb DVT treated by anticoagulant. Full engraftment on D+18. Follow-up FDG PET/CT on D+380 showed metabolically active circumferential mural thickening of the distal rectum (SUV 4) and multiple low metabolically active peri-rectal and presacral suspicious lymph node. Despite FDG PET/CT having a significant role in the hematological patients' management, positive lymph nodes and metabolically active masses require histologic assessment to avoid incorrect diagnosis. The patient was referred for colonoscopic assessment for these newly developed lesions which revealed suspicious malignant rectosigmoid masses with multiple small sessile polyps, and abnormal mucosal patterns all over the colon. Colonic biopsy revealed snips of colonic mucosa, the lamina propria is widened by dead and living bilharzial ova and surrounding dense inflammatory cellular infiltrate formed of eosinophils and lymphoplasmacytic cells, this picture consistent with bilharzial colitis, no atypia or malignancy was detected. The patient started anti-bilharzial therapy and on follow up. ASCT plays a central role in the treatment of diverse diseases. Infection is one of the major causes of morbidity and costs of the procedure, representing the 2nd cause of death after primary disease.

AML-197 Incidence of Infectious Lung Disease in Neutropenic Patients

Immunosuppression caused by hematologic malignancies can affect all cell lines, but profound neutropenia is the main risk factor. The most common infection is pneumonia. More than 60% of neutropenic patients develop a lung infection. These infections develop in 13-31% of patients during induction chemotherapy for acute myeloid leukemia (AML). They are associated with a significantly higher mortality rate than other infectious diseases. Deduce the incidence of infectious lung disease in our neutropenic patients. This is an observational, descriptive, and prospective study carried out in the Department of Hematology and Pediatric Oncology 20 August of Casablanca, spread over a period of 10 months, from 01 May 2019 to 29 February 2020. It focuses on adult patients over 18 years of age with neutropenia (a PNN count < 2×109/L) hospitalized in the protected unit (AML and aplastic anemia) and the transplant unit, who presented an episode of infectious lung disease during the study period. We determined the incidence and studied the clinical and radiological presentation, the diagnostic steps to obtain biological and microbiological documentation, and the final evolution of these infectious episodes. Out of a total of 235 admissions, 50 episodes of infectious lung disease were identified in 49 patients, for an overall incidence of 21.28%. The most frequent phase of treatment was that of Induction in AML. Thoracic CT was performed in all patients. Bronchoalveolar lavage was performed over 9 episodes. The results were positive in 44.5% of episodes. Serum galactomannan antigenemia assay was performed in 94% of cases, it was positive in 22 (46%). The GeneXpert technique was performed in six episodes (12%), with one positive result. The probable fungal infection was the cause of these infections in 58% of cases. Bacterial pneumopathy was present in 22% of episodes. Pulmonary tuberculosis was diagnosed in only one patient. Pneumocystis was suspected in 4 episodes and viral infection was suspected in 3 episodes. The evolution was favorable in 52% of the cases. The review of the literature has shown that the establishment of an etiological diagnosis is not always possible during these infections, the treatment is essentially empirical, and with a terrible prognosis.

An Australian perspective on antimicrobial stewardship programs and transplantation.

Over 1000 solid-organ and close to 2000 stem-cell transplants are performed annually in Australia. Antimicrobial stewardship activities in transplant units in Australia were reviewed. All health service organizations, and thus all transplant centers, in Australia are required to have an antimicrobial stewardship program. Despite this, in one recent survey, 23.5% of hospital antibiotic prescriptions were inappropriate. Vigorous efforts are being made to implement antifungal stewardship in Australian transplant programs, with guidelines for implementation published in December 2021. These guidelines include therapeutic antifungal drug monitoring and diagnostic stewardship as it pertains to the investigation of suspected invasive fungal infections. Infections with multidrug resistant pathogens and invasive fungi are sporadic issues in Australian transplant units, but stewardship efforts can optimize patient outcomes.

Current state of antimicrobial stewardship in organ transplantation in Singapore

Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, "handshake stewardship", is more appropriate. To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.

Reducing central-line associated bloodstream infections (CLABSIs) through patient accountability contracts: A pilot project for patients on Weill Cornell Medicine (WCM) bone marrow transplant (BMT) service.

283 Background: Patients with cancer whom develop Central Line Associated Blood Stream Infections (CLABSIs) have increased mortality rates ranging from 12% to 40%. Transplant patients are particularly at risk due to cytotoxic chemotherapy regimens and/or graft-versus-host disease with risk for translocation of oral and gut flora to the bloodstream. At Weill Cornell Medicine, we had 102 CLABSIs in 2021, 25 (25%) of which attributed to patients in oncology units. The Bone Marrow Transplant (BMT) Unit, had 10 of the 25 (40%), 2.05 CLABSIs per 1000 central line inpatient days with a CLABSI standardized infection ratio (SIR) of 1.26 (above goal of 1). Methods: Our SMART aim was to reduce the number and rate of CLABSI events on the BMT unit by 10% from February 1, 2022 – June 30, 2022 by educating patients on preventive strategies and implementing a patient central-line maintenance “contract.” We had previously optimized evidence-based nursing interventions for CLABSI prevention which included adherence to central line maintenance best practices, weekly device rounds with Infection, Protection &amp; Control to monitor compliance with dressing changes and IV tubing, annual CLABSI prevention competencies, peer-to-peer validation of blood culture lab draws, weekly quality-improvement huddles and interdisciplinary root cause analysis discussions for CLABSI events. Patient noncompliance with daily recommendations for central line care was identified as a possible CLABSI risk factor that was not previously addressed in the bundle. Newly-developed patient education and a “contract” was incorporated into the BMT admission process. Results: The BMT CLABSI patient education and contract was initiated with all new patients admitted to unit in February 1, 2022. Since starting, the BMT unit CLABSI SIR has decreased from 1.26 to 0.6, and from a CLABSI rate per 1000 central lines days of 2.05 to 0.97. Conclusions: Engaging patients in their own care of the central lines can significantly reduce overall risk of central line infections. Patients have positively responded to this pilot project. We have translated educational materials and contracts to other languages and are considering expansion into other units.

Antimicrobial stewardship in pediatric solid organ transplantation: Is it possible?

Solid organ transplant (SOT) recipients are at increased risk of severe outcomes associated with antimicrobial resistance (AMR). Antimicrobial stewardship programs (ASPs) play a vital role in mitigating the negative impacts of AMR. Pediatric evidence regarding ASP for SOT recipients is scarce, although many pediatric SOT centers have implemented different forms of ASP. This article summarized the available evidence relating to AMR among pediatric SOT recipients and discussed key strategies for the successful implementation of ASP among this population. The focus is primarily on antibacterial and secondarily on antifungal management. The development of multidisciplinary antimicrobial stewardship teams for pediatric SOT recipients is essential for successful stewardship implementation. Key stakeholders may include but are not limited to SOT recipients and their caregivers, primary SOT teams (transplant physicians, transplant pharmacists, transplant unit nurses, and transplant outpatient care team), transplant surgery teams, transplant infectious diseases teams, hospital AST, microbiology teams, infection prevention teams, quality improvement teams, and information technology teams. As the evidence for optimal ASP in pediatric SOT is still evolving, it is important to measure the impact of implemented interventions.

AML-199 Radiological Aspects of Pneumonias in Neutropenic Patients

Imaging, such as chest X-ray and chest CT scan, plays a pioneering role in the diagnosis of neutropenic patients with respiratory dysfunction. To analyze radiographic patterns of adults with prolonged neutropenia and pneumonia. An observational, descriptive, and prospective study that analyzed patients admitted to the protected unit (acute myeloid leukemia and aplastic anemia) and transplant unit of Hematology and Pediatric Oncology at August 20th Hospital in Casablanca, from May 1st, 2019 to February 29th, 2020. Patients included were 18 years of age or older receiving chemotherapy and then developed respiratory symptoms during the period of neutropenia. An exploitation form was used to acquire the data then its analysis was performed with IBM SPSS Statistics version 21. Chest X-rays were taken during 20 of the 50 episodes of pneumonia (40%). They were all pathological, including alveolar opacities (90%), excavation (5%), reticulonodular (15%), and effusion syndrome fluid (15%). Chest computed tomography (CT scan) was performed in all patients. The time of its realization from the appearance of signs call clinics was variable ranging from 0 to 8 days, with a median of 2 days. It is important to note that distinct picture radiographs can coexist on the same X-ray and in the same patient. Forty six percent of our patients had condensation hearth and micronodules, nodules (58%), ground-glass opacity (60%), fluid effusion (34%), mediastinal lymphadenopathy (30%), interstitial thickening (22%), and 16% had reticulonodular infiltrates. Eight patients (16%) in our study had Halo sign, 10% had cavity image as well as Atelectasis, 2% with tree-in-bud aspect, and 2% had centrilobular emphysema. Thoracic CT improves the quality of the diagnosis; it also contributes to better management of neutropenic patients when pneumonia is suspected.

CT-025 Impact of Stem Cell Source on Outcome of Allogeneic Stem Cell Transplantation in Pediatric Cancer

Allogeneic hematopoietic stem cell transplantation is an established option of therapy for many malignant and non-malignant diseases which involve the hematopoietic and immune systems. The numbers of patients who are eligible for this procedure are continuously increasing due to the better supportive care and the developments in the use of alternative donors and stem cell sources. A retrospective study included 159 patients transplanted at bone marrow transplantation unit, children cancer hospital Egypt (CCHE) 57357. All patients with high risk hematological malignancy were considered eligible. Stem cell source obtained for these patients was either bone marrow (BM) or peripheral blood (PB). HLA matching was either matched related donor (MRD) or haploidentical transplant. Impact of stem cell source on the outcome of these patients was analyzed. BM was the most commonly used graft source in 92.5% of cases with OS of 81.9% and EFS of 70.9%. PB was only used in 7.5% with 50% OS and 33.3% EFS (P value =0.021). MRD was used in 86% of patients, while 10.1% received their allograft from haploidentical donors. At the end of the study 64.8% of the patients were alive, 34.6% died while only one patient lost follow up. With median duration of follow up of 64 months, the 3-year overall survival of the whole patients was 64% Conclusions: Bone marrow has a better survival outcome as a source of stem cell in allogeneic SCT than peripheral blood. However, it should be noted than PB SCT was used in Juvenile myelomonocytic leukemia patients which is known to have the worst outcome when transplanted.

A plethora of ocular surface manifestations in a multidisciplinary ocular graft-versus-host disease unit

To describe the experience in a recently created ocular graft-versus-host disease unit in a tertiary hospital and to detail ocular surface features and complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study included all patients who underwent allo-HSCT, with or without chronic GVHD and were being monitored in the Hematopoietic Stem Cell Transplantation Unit in the UNICAMP Clinical Hospital (Campinas, Sao Paulo, Brazil) from 2015 to 2020. Patients were concomitantly evaluated by hematology and ophthalmology teams of the Ocular GVHD Unit. Hematologists performed a comprehensive systemic evaluation searching and grading mouth, skin, lungs, gastrointestinal tract, liver and genitalia GVHD. While ophthalmologists evaluated ocular symptoms through specific questionnaire (Ocular Surface Disease Index—OSDI) and a protocol of distinct ocular surface parameters for dry eye disease (1) and ocular complications, which encompassed meniscometry, non-invasive tear break-up time (NITBUT) measurement, conjunctival hyperemia quantification, meibography, fluorescein and lissamine staining and Schirmer’s test. Patients were diagnosed with chronic GVHD using the National Institutes of Health (NIH) Consensus Criteria for Chronic Graft-versus-Host Disease. The International Chronic Ocular GVHD Consensus Group (ICOGCG) score was obtained at the onset of ocular disease presentation or afterwards. A total of 82 patients underwent allo-HSCT (97.6% full matched and 2.4% haploidentical), mainly for cases of leukemia and 73.2% had chronic GVHD. Mean onset time for chronic GVHD was 232 ± 7.75 days. The mouth, skin, and eyes were the main organs involved (63%, 50%, and 48%, respectively). Symptom scores and all ocular surface parameters differ in patients with and without chronic GVHD and along different timepoints of the follow-up. Ocular complications mostly involved were severe DED and meibomian gland dysfunction, conjunctival scarring, cataract and infections resulting in keratitis and corneal perforation. As therapeutic strategies, 73% patients received preservative-free lubricants, 27% autologous serum, 48% topical steroids, 27% oral tetracycline derivatives, 22% mucolytic eye drops and 3 patients needed bandage contact lens. Ocular GVHD is a complex and challenging disease with varied manifestations, resulting in a broad range of ocular test endpoints, and inconsistent treatment responses. The main ocular presentations were dry eye, meibomian gland dysfunction and cataracts. The therapeutic approach often involves topical steroids and autologous serum tears. It is important to monitor these patients closely, so the ocular GVHD Unit may improve the care, providing prompt identification of ocular manifestations and faster treatment of complications.