Transplant-related Complications Research Articles

How to cultivate sustainable physical health and wellness in transplant recipients: the emerging and enduring role of exercise scientists.

The aim of the current review is to highlight the importance of exercise training as an important section of transplant recipient rehabilitation process and explain the role of the exercise scientist in the development, implementation, and assessment of the exercise regime. Transplant patients face a unique set of challenges in their recovery and rehabilitation process, often requiring a multifaceted approach to address the physical, emotional, and psychological aspects of their condition. Exercise training has emerged as a crucial component in the care of these patients, providing a means to improve functional capacity, enhance quality of life, and mitigate the adverse effects of transplant-related complications. Exercise scientists who are trained to assess patient's physical limitations, develop and deliver personalized exercise programs, and monitor their progress are uniquely positioned to play a crucial role in the treatment of patients with chronic conditions that require exercise training as a mean of improving and maintaining health and quality of life. Exercise scientists are the appropriate professionals for providing transplant recipients with the recommended exercise training for maintaining and improving their health status as part of the overall plan of long-term care and support.

Transplantation for type 1 diabetes: radiologist's primer on islet, pancreas and pancreas-kidney transplantation imaging.

Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications.

Late nephrectomy in infants with congenital nephrotic syndrome of the Finnish type.

Bilateral nephrectomy is commonly performed in patients with congenital nephrotic syndrome of the Finnish type. The optimal timing of nephrectomy is unclear. Growth, thromboembolic events, infections, transplant-related complications and ability to eat were compared between infants with early (Group 1, n = 13) and late (Group 2, n = 10) nephrectomy. 'Early' was defined as nephrectomy at 7-kg body weight followed by peritoneal dialysis and 'late' as nephrectomy at ≥10 kg followed by 3-4 weeks of haemodialysis and kidney transplantation. Patients were followed until the end of the first post-transplant year. Dialysis time was significantly longer in group 1 than in group 2. Late nephrectomy did not increase the risk for thromboembolic events or septicaemia but decreased tube feeding dependency (group 1 69% vs. group 2 20%, p = 0.019). Motor development at transplantation was considered normal in 80% of the infants with late nephrectomy compared to 31% in the early nephrectomy group (p = 0.019); however, the difference between the groups disappeared by the end of the follow-up. Infants with late nephrectomy have comparative outcome but less feeding tube dependency and better motor development during the first post-transplant months compared to infants with early nephrectomy.

Mesenchymal stromal cells in the treatment of pediatric hematopoietic cell transplantation-related complications (graft vs. host disease, hemorrhagic cystitis, graft failure and poor graft function): a single center experience.

To describe mesenchymal stromal cells (MSCs) in the treatment of hematopoietic stem cell transplantation (HSCT) complications and to assess its safety and efficacy. Single-center retrospective study (2016-2023). Patients under 20 years who received MSCs for the treatment of HSCT-related complications were included. Thirty patients (53.7% boys), median age at transplant 11 years (range 2-19) were included. MSCs indications were: graft-vs.-host disease (GVHD) in 18 patients (60%), of them 13 had acute GVHD (43.3%) and 5 chronic GVHD (16.7%); Grade 3-4 hemorrhagic cystitis (HC) in 4 (13.3%); poor graft function (PGF) in 6 (20%), 5 of them receiving MSCs with a CD34 stem cell-boost coinfusion; graft failure (GF) in 2 (6.7%), to enhance engraftment after a subsequent HSCT. Infusion-related-adverse-events were not reported. Overall response (OR) was 83% (25/30); 44% of responders (11/25) showed complete response (CR). OR for GVHD, HC, PGF and GF was 83.3%, 100%, 66.7% and 100% respectively. Response rate was 40% (95% CI: 20-55) and 79% (95% CI: 57-89) at 15 and 30 days. With a median follow-up of 21 months (IQR11-52.5), overall survival (OS) was 86% (95% CI: 74-100) and 79% (95% CI: 65-95) at 6 and 12 months post-MSCs infusion. In our study, the most frequent indication of MSCs was refractory aGVHD (43.3%). Response rates were high (OR 83%) and safety profile was good.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3+CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3-CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.

Allogeneic hematopoietic stem cell transplantation after mogamulizumab in T-cell lymphoma patients: a retrospective analysis

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapy for patients with T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL), adult T-cell lymphoma (ATL), and peripheral T-cell lymphoma (PTCL). Mogamulizumab is an anti-CCR4 antibody that has been associated with an increased risk of transplant-related complications in retrospective analyses of ATL, particularly when administered within 50 days before transplantation. This post hoc analysis of 3 clinical trials examined safety and outcome data for 32 patients with CTCL (n = 23), ATL (n = 7), or PTCL (n = 2) who underwent allo-HSCT after mogamulizumab treatment. Overall, 22 patients (69%) were known to have graft-versus-host disease (GVHD), 8 patients (25%) did not report GVHD, and 2 patients (6%) had unknown GVHD status. Fourteen patients with known GVHD underwent transplantation between 50 and 365 days after their last dose of mogamulizumab, while 2 underwent transplantation within 50 days after treatment. Based on this limited evidence, GVHD was not associated with the time interval from last mogamulizumab dose to transplantation.

Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Application of Mass Cytometry Platforms to Solid Organ Transplantation.

Transplantation serves as the cornerstone of treatment for patients with end-stage organ disease. The prevalence of complications, such as allograft rejection, infection, and malignancies, underscores the need to dissect the complex interactions of the immune system at the single-cell level. In this review, we discuss studies using mass cytometry or cytometry by time-of-flight, a cutting-edge technology enabling the characterization of immune populations and cell-to-cell interactions in granular detail. We review the application of mass cytometry in human and experimental animal studies in the context of transplantation, uncovering invaluable contributions of the tool to understanding rejection and other transplant-related complications. We discuss recent innovations that have the potential to streamline and standardize mass cytometry workflows for application to multisite clinical trials. Additionally, we introduce imaging mass cytometry, a technique that couples the power of mass cytometry with spatial context, thereby mapping cellular interactions within tissue microenvironments. The synergistic integration of mass cytometry and imaging mass cytometry data with other omics data sets and high-dimensional data platforms to further define immune dynamics is discussed. In conclusion, mass cytometry technologies, when integrated with other tools and data, shed light on the intricate landscape of the immune response in transplantation. This approach holds significant potential for enhancing patient outcomes by advancing our understanding and facilitating the development of new diagnostics and therapeutics.

Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association.

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide

BackgroundRecombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. ObjectiveWe aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). Study DesignSAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. ResultsAll 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein–Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. ConclusionrhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?

The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates. Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality. Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups. Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.

Immunological Landscapes in Lung Transplantation: Insights from T Cell Profiling in BAL and PBMC.

Lung transplant recipients frequently encounter immune-related complications, including chronic lung allograft dysfunction (CLAD). Monitoring immune cells within the lung microenvironment is pivotal for optimizing post-transplant outcomes. This study examined the proportion of T cell subsets in paired bronchoalveolar lavage (BAL) and peripheral PBMC comparing healthy (n = 4) and lung transplantation patients (n = 6, no CLAD and n = 14 CLAD) using 14-color flow cytometry. CD4+ T cell proportions were reduced in CD3 cells in both PBMC and BAL, and positive correlations were discerned between T cell populations in peripheral PBMC and BAL, suggesting the prospect of employing less invasive PBMC sampling as a means of monitoring lung T cells. Furthermore, regulatory T cells (Tregs) were enriched in BAL when compared to peripheral PBMC for transplant recipients. A parallel positive correlation emerged between Treg proportions in BAL and peripheral PBMC, underscoring potential avenues for monitoring lung Tregs. Finally, the most promising biomarker was the Teff (CD8+Granzyme B+)-Treg ratio, which was higher in both the PBMC and BAL of transplant recipients compared to healthy individuals, and increased in the patients with CLAD compared to no CLAD and healthy patients. Conclusions: Distinct T cell profiles in BAL and peripheral PBMC underscore the significance of localized immune monitoring in lung transplantation. The Teff (CD8+granzyme B+)-Treg ratio, particularly within the context of CLAD, emerges as a promising blood and BAL biomarker reflective of inflammation and transplant-related complications. These findings emphasize the imperative need for personalized immune monitoring strategies that tailored to address the unique immunological milieu in post-transplant lungs.

Long-term changes in cardiac remodelling in prevalent kidney graft recipients

BackgroundApproximately 15% of kidney transplant (KT) recipients develop de novo heart failure after KT. There are scarce data reporting the long-term changes in cardiac structure and function among KT recipients. Despite the improvement in renal function, transplant-related complications as well as immunosuppressive therapy could have an impact on cardiac remodelling during follow-up. We aimed to describe the long-term changes in echocardiographic parameters in prevalent KT recipients and identify the clinical and laboratory factors associated with these changes. MethodsA centralised blinded review of two echocardiographic examinations after KT (on average after 17 and 39 months post-KT respectively) was performed among 80 patients (age 50.4 ± 16.2, diabetes 13.8% pre-KT), followed by linear regression to identify clinico-biological factors related to echocardiographic changes. ResultsLeft atrial volume index (LAVI) increased significantly (34.2 ± 10.8 mL/m2vs. 37.6 ± 15.0 mL/m2, annualised delta 3.1 ± 11.4 mL/m2/year; p = 0.034) while left ventricular ejection fraction (LVEF) decreased (62.1 ± 9.0% vs. 59.7 ± 9.9%, annualised delta −2.7 ± 13.6%/year; p = 0.04). Male sex (β = 8.112 ± 2.747; p < 0.01), pre-KT hypertension (β = 9.725 ± 4.156; p < 0.05), graft from expanded criteria donor (β = 3.791 ± 3.587; p < 0.05), and induction by anti-thymocyte globulin (β = 7.920 ± 2.974; p = 0.01) were associated with an increase in LAVI during follow-up. Higher haemoglobin (>12.9 g/dL) at the time of the first echocardiography (β = 6.029 ± 2.967; p < 0.05) and ACEi/ARB therapy (β = 8.306 ± 3.161; p < 0.05) were associated with an increase in LVEF during follow-up. ConclusionThis study confirms the existence of long-term cardiac remodelling after KT despite dialysis cessation, characterised by an increase in LAVI and a decrease in LVEF. A better management of anaemia and using ACEi/ARB therapy may prevent such remodelling.

Pediatric patients on veno-arterial extracorporeal membrane oxygenation undergoing cardiac rehabilitation have better outcomes

BackgroundThe importance of physical rehabilitation in optimizing outcomes in critically ill patients is recognized. However, the frequency and benefit of mobilization in pediatric patients undergoing veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is unclear. This study evaluates a cohort of pediatric VA-ECMO patients to characterize the spectrum of mobility and evaluate associations of mobilization with clinical outcomes. MethodsWe analyzed 688 patients (8-18yrs) who underwent primary ECMO runs and had mobilization data collected in the Extracorporeal Life Support Organization (ELSO) Registry. Demographics, pre-ECMO support, location and duration of support, and outcomes including survival to hospital discharge, heart transplant, and ECMO related complications were collected. Propensity score modeling was performed with entropy weighting to compare outcomes between mobile and non-mobile patients. ResultsOf the 688 patients included, 10% achieved some degree of mobility (69/688); the majority of those exercised in bed. After propensity score matching, mobility was associated with an increased likelihood of being discharged alive (OR 1.16, 95% CI 1.04, 1.30) and receiving a heart transplant (OR 1.15, 95% CI 1.02, 1.29), and a lower likelihood of dying on ECMO (OR 0.90, 95% CI 0.81, 1.00). There was no association between mobility and ECMO being discontinued due to complication (OR, 1.03 95% CI 0.97, 1.10). ConclusionMobilization in a pediatric VA-ECMO cohort was achieved by 1/10 patients, is associated with heart transplant and survival to hospital discharge and is not associated with ECMO related adverse events. Mobility in certain pediatric VA-ECMO patients is feasible and may represent an opportunity to improve outcomes.

Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn's Disease

Background & aimsDurable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications. MethodsDNA from patients and their HLA-matched unrelated donors was genotyped and Polygenic Risk Scores calculated. Donor marrow was infused following non-myeloablative conditioning. Patient symptoms and endoscopic findings were documented at intervals after transplant. ResultsWe screened 807 patients, 143 of whom met eligibility criteria; 2 patients received allografts. Patient 1 had multiple complications and died at day 332 from respiratory failure. Patient 2 had resolution of CD symptoms until day 178 when CD recurred, associated with persistent host chimerism in both peripheral blood and intestinal mucosa. Withdrawal of immune suppression was followed by dominant donor immune chimerism in peripheral blood and resolution of CD findings. Over time, mucosal T-cells became donor-dominant. At 5 years after allografting, Patient 2 remained off all medications but had mild symptoms related to a jejunal stricture that required stricturoplasty at 6 years. At 8 years, she remains stable off medications. ConclusionsThe kinetics of immunologic chimerism after allogeneic marrow transplantation for CD patients depends on the intensity of the conditioning regimen and the magnitude of immune suppression. One patient achieved durable improvement of her previously refractory CD only after establishing donor immunologic chimerism in intestinal mucosa. Her course provides proof-of-principal for allografting as a potential treatment for refractory CD, but an immunoablative conditioning regimen should be considered for future studies.(ClinicalTrials.gov, NCT01570348)

Impact of Kidney Transplantation-related Complications on Patient and Graft Outcomes in Early Period

Böbrek nakli sonrası erken dönem hasta ve graft sağkalımı, birbiriyle ilişkili birçok karmaşık faktöre bağlıdır. Bu çalışmada; canlı ve kadaverik vericiden böbrek nakli yapılan hastalarda intra- ve post-operatif gelişen medikal ve cerrahi komplikasyonların sıklığı ve bu komplikasyonların erken dönemde hasta ve graft sağkalımı üzerine olan etkileri araştırıldı. Tek merkezde on yıllık dönemde böbrek nakli yapılan 498 hasta verileri retrospektif olarak incelendi. Alıcıların demografik, diyaliz ve nakil bilgileriyle, intra- ve post-operatif komplikasyonlar tıbbi kayıtlardan elde edildi. Komplikasyon gelişimi ile hasta ve graft sağkalımını etkileyen risk faktörler değerlendirildi. Çalışmamızda, canlı vericili nakillerde intra-operatif cerrahi komplikasyon, kadaverik vericili nakillerde post-operatif medikal ile post-operatif medikal ve cerrahi komplikasyon sıklığı anlamlı olarak yüksek saptandı. Gündüz çalışma saatleri dışında yapılan operasyonlarda post-operatif medikal komplikasyonlar daha sık görüldü. Post-operatif cerrahi komplikasyon ile post-operatif medikal ve cerrahi komplikasyon görülmesi ise istatistiksel olarak graft sağkalım süresini ve hasta sağkalım süresini anlamlı olarak kısalttı. İntra-operatif medikal ve cerrahi komplikasyon gelişiminde; verici yaşındaki 1 birimlik artış komplikasyon riskini 1.027 kat arttırdı. Nakil öncesi diyaliz modalitesinin hemodiyaliz olması, periton diyalizi olmasına kıyasla intraoperatif medikal ve cerrahi komplikasyon gelişme riskini 3.816 kat arttırdı. Sonuç olarak, gözlemlerimiz erken dönemde medikal ve cerrahi komplikasyonların sık görüldüğünü ve bu komplikasyonların hasta ve graft sağkalımını etkileyebileceğini düşündürmektedir.

Meta-analysis of decitabine pretreatment-based allogeneic hematopoietic stem cell transplantation affecting transplantation-related complications and prognosis in patients with malignant hematological disease.

Malignant hematological diseases (MHD) are a kind of bone marrow hematopoietic system disease caused by malignant clonal proliferation, including leukemia, lymphoma, myelodysplastic syndrome, etc. At present, there are too few meta-analyses on the effect of decitabine pretreatment-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) on transplantation-related complications and prognosis of MHD patients. A systematic search of PubMed, MEDLINE, Science Direct, The Cochrane Library, CNKI, and CBM was performed. The relevant literature on decitabine pretreated allo-HSCT for the treatment of MHD was screened, and the screening time was up to May 1, 2023. After extensive investigation, only 5 articles met the criteria. Result: The results of this article showed that the odds ratio of mortality after decitabine conditioning treatment was 2.35, the incidence of complications after transplantation was 1.07, and the survival rate following transplantation was 0.82. Decitabine-based conditioning regimen can reduce the incidence of transplantation-related complications and improve the prognosis of MHD patients receiving allo-HSCT. Although it has limitations, it still has very important clinical implications.

Clinical Features of Myeloid Neoplasms with Germline GATA2 Mutations–a Systematic Review of Clinical Studies Retrieved through Extensive Searching

Aims: Recent findings increasingly find individuals are being recognized as having germline predisposition to myeloid malignancies. GATA2 mutation is one of the most extensively studied germline mutations. However, until recently most of studies have focused on the mechanism of how GATA2 as one of the driver mutations causes malignancies. As regards the clinical features, such as the treatment and prognosis of myeloid neoplasms associated with germline GATA2 mutations, only small studies published, based on which they were insufficiently studied. Therefore, we did the systematic review to summarize the diagnosis, therapeutic methods and prognosis of myeloid malignant diseases associated with germline GATA2 mutations. Methods: Two reviewers independently comprehensively searched Pubmed and hand searched the professional journals and the reference lists of related and included articles from Jan 1 st, 1990 until May 1 st, 2023. They also independently screened and evaluated the retrieved records and then extracted data of included studies. Studies reported clinical materials on the diagnosis, treatment and prognosis of myeloid malignant patients with germline GATA2 mutations will be included and the clinical data will be summarized. Searching strategies were as follows: #1 germline or predispo* or somat* or famil* or germ line or congenit* or altera* or non-tumor; #2 gene* or genom* or sequenc* or muta* or SNP or abnormal* or translocat* or chromosom* or frameshift* or exom* or GATA; #3 “acute myeloid leukemia” “Leukemia, Myeloid, Acute” “Myelodysplastic Syndromes” “refractory anemia” “myeloid or myeloblast*” or AML or MDS; #4 #1 and #2 and #3 Results: 2457 records were retrieved and 23 studies with 396 patients were included. Screening process was shown in Figure 1. Studies included were all small sample sized. The diagnosis age was from three to 78 years old, most of the median ages of included studies were less than 30 years indicated carriers would have symptoms in young age, on the other hand, there were also patients who began having symptoms in old age (the oldest 78 years) or remained asymptomatic carriers without getting sick in the whole life. There was no sex difference. Emberger syndrome which caused lymphedema and MonoMAC and/or DCML (dendritic cell, monocyte, B-lymphocyte and NK-lymphocyte) deficiency syndromes that caused cytopenia and infections were generally appeared earlier before myeloid malignancies. Myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) are common malignant diseases for patients with germline GATA2 mutations predisposition. The morbidity was not able to be calculated based on the data available. MDS was the most common myeloid neoplasm compared with AML and CMML which were always transformed from MDS. Other hematologic malignancies were rare. The disease transformation was shown from refractory cytopenia to malignant clonal hematopoiesis that caused MDS, and then transformed into leukemia. In total, 311/396 (78.5%) patients developed malignant myeloid diseases. Nine studies had done the family pedigree analysis and there were 162 family members who had the germline GATA2 mutations predisposition, in which there were 32 asymptomatic carriers (19.7%). 128 patients were reported to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT), 81 (63.3%) were alive and 44 (34.4%) died of relapse or transplantation related complications. Three patients' outcome was unknown. In study Michael A. Spinner et al, survival rate was 54% by 4 years after allo-HSCT (21 patients included). Nearly all patients (15/18) with myeloid malignancies who did not receive transplantation had died. The most common cytogenetic abnormalities were monosomy 7 and trisomy 8, and other abnormalities were also common. Conclusions: Most of germline GATA2 mutation carriers will have symptoms in young age and many of them will progress into malignant myeloid diseases. Allo-HSCT was effective to treat symptomatic patients, especially for patients with malignant hematologic diseases, and furthermore that is the only curative treatment. Asymptomatic carriers are not rare and for them regular tests are essential. More clinical studies on germline GATA2 mutations for myeloid neoplasms are needed to clarify the clinical features in this setting and improve its treatment and prognosis.

Bone Marrow Versus Peripheral Blood in HLA-Matched Sibling Transplantation: Does the Stem Cell Source Matter in Severe Aplastic Anemia?

Background Selecting a graft source is critical in HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HCT) for severe aplastic anemia (SAA). Since graft-versus-host-disease (GVHD) is the major cause of mortality after MSD-HCT, and SAA patients do not need the graft-versus-leukemia effect, the selection of a suitable source of stem cells becomes critical. Although bone marrow (BM) is the preferable stem cell source based on the registry-based studies, mobilized peripheral blood stem cells (PBSC) may offer faster engraftment with rapid immune reconstitution. Moreover, the recent advances in conditioning regimens have significantly reduced transplantation-related complications. Here, we compared the long-term outcomes of BM vs PBSC as a graft source in adult patients with SAA who received MSD-HCT with the reduced intensity conditioning (RIC) regimen. Method We conducted a retrospective analysis of 171 consecutive SAA adult patients who received MSD-HCT with Flu6/Cy2/ATG4 RIC regimen (Flu, 30 mg/m 2 IV for 6 days: Cy, 50 mg/kg IV for 2 days; rabbit ATG, 2.5 mg/kg IV for 4 days) or total nodal irradiation (TNI) of 750 cGy combined with ATG as GVHD prophylaxis (TNI-750/ATG) from March 2002 to March 2021 at Seoul St. Mary's Hospital, Seoul, Korea. BM was the primary graft source, but PBSC was used in donors who refused BM harvest, were unsuitable for general anesthesia, or received TNI-750/ATG conditioning. The primary endpoint of this study was to compare the overall survival (OS), and the secondary endpoints included speed of hematologic recovery, primary or secondary graft failure (GF), and failure-free survival (FFS) between the BM and PBSC group. Results The median patient age in the BM group was 38 years (range, 15 - 59) and 44 years (range, 19 - 64) in the PBSC group (p=0.005). There were no differences of baseline characteristics between the two groups except for a donor-to-recipient sex discrepancy (female to male, BM vs. PBSC; 16.4% vs. 30.9%, p=0.029). The majority of BM group (114/116, 98.2%) received the Flu6/Cy2/ATG4 RIC regimen, while 38.2% (21/55) of PBSC group received TNI-750/ATG for the conditioning (p&amp;lt;0.001). The PBSC contained a median 4.71 (range, 1.22 - 17.03) x 10 6/kg CD34 + cells and 368.82 (range, 25.12 - 1234.70) x 10 6/kg CD3 + cells which were about 1.7-fold (BM 2.80 x 10 6/kg CD34 + cells; range, 0.25 - 10.05) and 10-fold (BM 39.61 x 10 6/kg CD3 + cells; range, 1.34 - 463.68) higher than the BM graft (p&amp;lt;0.001). Consequently, the PBSC group exhibited faster engraftment of neutrophils (median 13 vs. 11 days, p&amp;lt;0.001) and platelets (median 18 vs. 12 days, p=0.012). However, there were no differences in the incidence of secondary GF (19.0% vs. 12.7%, p=0.386) and donor-type aplasia (4.3% vs. 10.9%, p=0.178) between two groups. Furthermore, the incidence of acute grade I-II (8.6% vs. 10.9%, p=0.619) and moderate to severe chronic graft-versus-host disease (GVHD) (3.5% vs. 5.5%, p=0.542) were also not significantly different between two groups. However, the BM group has shown more CMV reactivation (44.0% vs. 24.9%, p=0.005), and higher incidence of respiratory infection (14.7% vs. 3.6%, p=0.037) than those of the PBSC group. The incidences of transplantation-related complications between the BM and PBSC group are summarized in Table. The 10-year OS (93.8% vs. 98.1%, p=0.246) and FFS (65.7% vs. 69.0%, p=0.455) were comparable (Figure). Moreover, there was no significant difference in FFS between BM and PBSC group by potential risk factors of patient and donor age at MSD-HCT, sex incompatibility, ABC mismatch, PNH clone presence, HCT-CI ≥3, infused CD34 + cell count, interval from diagnosis to transplant, prior IST history, heavy transfusion before allo-HCT, or severity of AA. Conclusions Our results suggest that survival outcomes of MSD-HCT showed no difference between BM and PBSC as graft sources, and using PBSC may be an efficient alternative offering faster engraftment without significant difference in graft failure or transplantation-related adverse events such as GVHD, and survival. Current analysis and results were drawn from the Asian population with a fludarabine-based conditioning regimen and therefore, need to validate in the Western population. In addition, well-designed prospective studies in a larger cohort are required to confirm our findings.