Complication Of Transplantation Research Articles

Incidence and Management of Posttransplantation Lymphoproliferative Disorder After Pediatric Solid Organ Transplantation: The Norwegian Experience.

Posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation (SOT) due to immunosuppression. In 2023, a pediatric PTLD register was established in Norway because of a perceived increase in the incidence of pediatric PTLD. This study aimed to analyze population-based data on the incidence and management of pediatric PTLD after SOT using the pediatric PTLD registry in Norway. This retrospective quality assurance study collected the data of pediatric patients with PTLD after SOT in Norway from January 1, 1995, to December 31, 2023. For comparison and calculation of incidence rates, SOT patients without PTLD required a minimum of 1 year posttransplant follow-up to be included. A total of 457 patients underwent SOT (57% males) and 22 (4.8%) developed PTLD (73% males). The median age at transplant in the SOT and PTLD groups were 9.5 (interquartile range, 2.4-14.5) and 4.3 (1.1-12.5) years, respectively. Twenty patients with PTLD (91%) were Epstein-Barr virus naive at the time of transplantation. Eighteen (82%) and four (18%) patients developed early and late PTLD, respectively. Ten patients had monomorphic PTLD (45%). All patients received a reduction in immunosuppression, 15 received rituximab, and six required chemotherapy. Six patients (27%) died after PTLD, five of whom had active PTLD disease at the time of death. None of the patients experienced graft loss. Our findings regarding the incidence, EBV status, sex, and age at transplantation align with those of previous studies.

Role of vesicoureteral reflux on pediatric kidney allograft function.

Vesicoureteral reflux (VUR) is a common urologic complication of pediatric kidney transplant, though there is little data on the effect of VUR on histologic graft changes or graft survival. All pediatric patients who received a kidney transplant from 2007 to 2020 were selected for retrospective chart review. All participants underwent a voiding cystourethrogram (VCUG) at a 6-month post-transplant. Patients were then categorized into two groups based on vesicoureteral reflux grade: no/low-grade VUR (grades 0-2) and high-grade VUR (grades 3-5). Outcomes collected included graft failure rates, graft function, urinary tract infections(UTIs), proteinuria, and Banff scores at 3- and 12-month post-transplant surveillance kidney biopsies. There were 74 pediatric patients who received a kidney transplant in the designated time-period, and of those 39 had no/low-grade VUR and 35 had high-grade VUR. There was no difference in graft failure among the two groups over time when stratified for age (p = 0.389, CI 0.53-5.08). Patients with high grade VUR had a higher risk of UTI development overall (RR 1.89, 95%CI 1-3.6, p = 0.041), mostly accounted for from increased development of febrile UTI (RR 1.66, 95%CI 1.1-2.6, p = 0.038). Unselected pediatric kidney transplant recipients with high-grade vesicoureteral reflux on VCUG at a 6-month post-kidney transplant are more likely to have febrile UTI compared to those in the low-grade VUR group. There is no difference in graft survival among the two groups.

How We Diagnose and Manage Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infection After Hematopoietic Cell Transplantation.

Herpes simplex virus (HSV) infection is a clinically significant complication in hematopoietic cell transplant (HCT) recipients. Refractory and resistant (R/R) HSV infections may occur in this patient population, particularly after prolonged exposure to anti-HSV agents. To provide a comprehensive review of the diagnostic approach and the treatment options for R/R HSV mucocutaneous infections in HCT recipients and to highlight future treatment strategies. We searched the PubMed Central Database and Embase to identify published studies on R/R HSV infections in HCT recipients. We used the search terms "herpes simplex virus," "resistant*," OR "refractory," "immunocompromised," "immunosuppress*," and "immunodeficien*," and screened the results for articles reporting R/R HSV infections among HCT recipients. We chose an HCT recipient with a complicated refractory HSV infection as a representative clinical case. A clear clinical definition of refractory HSV infection is currently not available, which can lead to delays in diagnosis and treatment, negatively impacting patient care. Apart from two small randomized controlled trials in the 1990s that looked at treatment with systemic foscarnet and topical cidofovir in patients living with human immunodeficiency virus, all treatment recommendations for R/R HSV infections are based on observational studies and case reports. The use of alternative treatment options often comes with serious side effects, such as kidney toxicity. This underscores the urgent need for safer and effective treatment options. Pritelivir, a new oral antiviral medication, is currently being studied in a phase 3 trial for R/R HSV infections in immunocompromised patients. Limited data from the Early Access Program, which allows compassionate use, suggests that pritelivir holds promise as a treatment option for HCT recipients with R/R HSV infections. The proposed R/R HSV mucocutaneous infection diagnostic and treatment algorithm guides the appropriate management of these difficult-to-treat infections, potentially improving patient outcomes.

Post-transplant Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation that significantly impacts graft and patient survival, occurring in 0.8-15% of transplant recipients. TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury due to endothelial damage and microthrombi formation in small vessels. However, clinical features can range from a renal-limited form, diagnosed only on a kidney biopsy, to full-blown systemic manifestations, which include neurological, gastrointestinal, and cardiovascular injury. TMA can arise due to genetic or acquired defects such as in complement-mediated TMA or can occur in the context of other conditions like infections, autoimmune diseases or immunosuppressive drugs, where complement activation may also play a role. Recurrent TMA after kidney transplant is almost always complement-mediated, although complement overactivation may also play a role in de novo post-transplant TMAs associated with ischemia-reperfusion injury, immunosuppressive drugs, antibody-mediated rejection, viral infections, and relapse of autoimmune diseases such as, antiphospholipid antibody syndrome. Differentiating between a complement-mediated process and one triggered by other factors is often challenging but critical to minimize allograft damage since the former is non-responsive to supportive therapy, needs long-term anti-complement therapy and has a high risk of recurrence. Given the central role of complement and impact of genetic defects on the risk of recurrence in many forms of post-transplant TMA, genetic testing for complement disorders is key for proper diagnosis and management. Given that complement activation may also play a role in a subset of TMAs associated with other conditions, prompt recognition and timely initiation of anti-complement therapy is equally important. Additionally, TMA associated with non-complement genes, often part of a broader syndromic process with distinct clinical features, has also been described. Early identification and treatment are essential to prevent graft failure and other severe complications. This review explores the pathophysiological mechanisms underlying various post-transplant TMAs.

Predictors of Posttransplant Lymphoproliferative Disease in Pediatric Patients.

Posttransplant lymphoproliferative disorder (PTLD) is a complication of pediatric solid organ transplantation. Benign adenotonsillar lymphoid hyperplasia confounds the ability to diagnose PTLD. Our aim was to identify factors that predict the presence of PTLD to inform decision-making regarding adenotonsillectomy. The electronic medical records at a quaternary children's hospital were queried over a 23-year period (2000-2023) for solid organ transplant patients that underwent tonsillectomy and/or adenoidectomy. Demographics, clinical presentation, and EBV serologies were analyzed to determine factors associated with presence of PTLD on final pathology. A total of 114 patients met inclusion criteria for analysis. Thirty-two of the 114 patients (28.1%) who underwent tonsillectomy and/or adenoidectomy had PTLD. Age at transplant, age at biopsy, sex, race, and type of organ transplanted were not found to be associated with development of PTLD. Patients with PTLD were more likely to have smaller tonsils, sore throat, fever, and tonsillar exudate; they were less likely to experience sleep disordered breathing. The immunosuppression agent used for induction and the number of maintenance immunosuppressive medications were not associated with the development of PTLD. Increased Epstein-Barr Virus (EBV) PCR copy number correlated to increased risk of developing PTLD (p < 0.003). Tonsillar hypertrophy and sleep disordered breathing are not necessarily indicative of the presence of PTLD. Suspicion for adenotonsillar PTLD should be based on symptomatology, clinical exam, EBV serologies, and degree of EBV PCR positivity. Sore throat, fever, tonsillar exudates, and significant elevation in EBV PCR copy number are particularly concerning for PTLD. 3 Laryngoscope, 2025.

Histopathological evaluation of renal allograft biopsies: a single center study in Dhaka, Bangladesh

Background: Renal transplantation is gradually increasing in Bangladesh due to introduction of live transplantation procedure in some of the urology centers in Dhaka. Graft dysfunction followed by graft failure is one of the worst complications of renal transplantation and graft biopsy is the gold standard to evaluate the cause of failure in addition to clinical parameters. This study was designed to evaluate the causes of graft dysfunction according to Banff classification and correlation with clinical and laboratory parameters. Methods: All the renal graft biopsy samples received at Armed Forces Institute of Pathology during the period from July 2020 to June 2022 were included in the study. Standard histological procedure for renal biopsy including special stains (PAS, Masson Trichrom, Silver) and DIF (IgG, IgA, IgM, C3, C1q, Kappa, Lambda) were applied for all the cases. Immunohistochemistry for C4d and CD3 were also performed for each case. Polyoma virus marker could not be evaluated due to unavailability. BANFF classification was done with the available findings. Results: Total 23 cases were included in this study. All the cases were from live related donors. Mean age of the patients was 34.39 years with male: female ratio 2.28. Time of kidney biopsy from renal transplantation varied from 7 days to 130 months with the average 27.66 months. Graft dysfunction was the indication of the biopsy with average serum creatinine 4.23 mg/dl (range 1.15 to 12.4 mg/dl). Ten (43.48%) of the patients had proteinuria ranging from 1.5 gm to 3 gm/24 hours and 7 (30.43%) patients had haematuria. Among all the cases, 10 (43.48%) came out as Banff category 2 (antibody mediated rejection, ABMR) among them 9 was acute ABMR and one was chronic ABMR. The next common Banff category was Banff 6 (6, 26.09%), which includes IgA nephropathy (2), MPGN (1), CNI toxicity (1), crystal nephropathy (1) and RCN (1). Three (13.04%) were diagnosed as Banff-4 (T cell mediated rejection, TCMR), one (4.34%) was Banff-3 (borderline) and one (4.34%) was Banff-5 (IFTA). Mixed category was observed in 2 cases (Banff-2 + Banff-6). None of the case was diagnosed as Banff-1. Mean age of ABMR was 34.92 years, average duration since transplantation was 20.93 months and mean serum creatinine level was 3.67 mg/dl. Mean age of patients having TCMR was 38.33 years, average duration from transplantation was 59.33 months and mean serum creatinine level 4.71 mg/dl. CNI toxicity was found in a female of 16 years after 10 days of transplantation. One 55 years diabetic male developed graft dysfunction due to crystal nephropathy. One 28-year-old male developed anuria after 7 days of transplantation and diagnosed as post transplant RCN. A 45-year-old male had graft dysfunction after 5 years of transplantation with very high serum creatinine level (12.4 mg/dl) diagnosed as IFTA. Conclusion: Acute ABMR was found to be the prime cause of graft rejection in this study which occured mostly within 2 years of renal transplantation. TCMR occured mostly after 3 years of transplantation. Graft dysfunction due to other than rejection covered 30.43% cases. BIRDEM Med J 2025; 15(1): 28-33

Steroid-resistant nephrotic syndrome due to renal-limited thrombotic microangiopathy and membranous nephropathy after allogeneic hematopoietic stem cell transplantation successfully treated with calcineurin inhibitors.

Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown. Herein, we report three cases of renal-limited TMA after allo-HSCT that presented with nephrotic syndrome, in which renal biopsy showed TMA and concurrent membranous nephropathy. All patients were refractory to glucocorticoid monotherapy and the addition of CNIs led to complete remission of nephrotic syndrome. Renal-limited TMA after allo-HSCT may present as nephrotic syndrome with distinct pathophysiological features from renal-limited TMA in non-allo-HSCT recipients. Previous reports have suggested that renal-limited TMA after allo-HSCT is associated with renal graft-versus-host disease, and thus optimizing immunosuppressive therapy, including CNI treatment, may be useful. CNI treatment may be an option even in the presence of renal-limited TMA after allo-HSCT accompanied by concurrent membranous nephropathy.

P-2274. Incidence and Microbiology of Postoperative Pleural Space Infections among Lung Transplant Recipients

Abstract Background Pleural space infections (PSI) represent a known complication of lung transplantation (LT) in the early posttransplant period. Within the historical literature, PSIs, and empyemas in particular, have been associated with an increased risk for death, with 29-43% 1-year mortality. However, these studies were small and conducted prior to advances in anti-infective prophylaxis and treatment strategies. Therefore, the purpose of this investigation was to characterize the microbial profile and outcomes of early PSI among lung transplant recipients (LTRs) within the modern era.Figure 1.Isolated organisms from pleural fluid of lung transplant recipients from present study (Panel A, 66 isolates, 2017-2022 transplants) and historical literature (Panel B, 4 studies, 55 isolates, 1983-2005 transplants) Methods This study was approved by the Institutional Review Board of St. Joseph’s Hospital and Medical Center (SJHMC). Included LTRs were transplanted between 2017-2022 at SJHMC with ≥ 1 pleural fluid culture positive for an organism within 90 days of LT. LTRs at SJHMC received cefepime, vancomycin, and levofloxacin in the immediate postoperative period, or targeted antibiotic therapy based on donor and recipient airway cultures. During the index transplant hospitalization, LTRs received prophylaxis with inhaled amphotericin and tobramycin. Additional opportunistic infection prophylaxis throughout the study period included valganciclovir, itraconazole, and trimethoprim/sulfamethoxazole. Results Among 554 total LTRs, 250 (45%) had pleural effusion cultures, and 54 (54/250, 22%) had ≥ 1 pleural culture positive for an organism (Table 1). Over 95% of effusions were exudative and 53% were neutrophil predominant. Of the 66 organisms isolated (Figure 1), 40 (61%) were Gram-positive bacteria, 21 (32%) were fungi (15 Candida species, 6 molds), 4 (6%) were Gram-negative bacteria, and 1 (2%) was unspeciated acid-fast bacilli. Infection was typically managed via effusion drainage and 4-6 weeks of pathogen-directed antimicrobial therapy. All-cause 1-year mortality was 7.4%, lower than national LTR 1-year mortality rates over the study period (∼10-12%). Conclusion In a large investigation of LTRs with early posttransplant PSIs, Gram-positive bacteria were isolated most frequently, with isolation of Candida also common. Gram-negative bacteria comprised a smaller proportion of infections than reported in prior literature. PSIs did not appear to predispose LTRs to poor posttransplant survival. Disclosures Michael D. Nailor, Pharm.D., InflaRx: Advisor/Consultant|Shionogi: Advisor/Consultant

Elderly Patients With Aplastic Anemia: Treatment Patterns and Outcomes in the Real World.

We retrospectively analyzed a large international cohort of 1113 patients with aplastic anemia to evaluate treatment choice and outcome in elderly patients as compared with a younger population. Overall, 319 (29%) patients were > 60 years old at diagnosis (60-64 years (n = 85), 106 65-69 years (n = 106), and 128 > 70 years (n = 128)). Elderly patients showed a more severe thrombocytopenia at onset and a significantly lower overall response (complete plus partial) to first-line therapy at 6 months as compared to younger patients (47% vs. 65%, p < 0.0001), irrespective of treatment modality (ATG or CyA combinations, eltrombopag, or androgens); 27 (8%) received transplant as second line therapy and 11 (41%) died, mainly due to transplant complications. The rate of evolution to MDS was greater in elderly patients (12% vs. 7% in younger AA, p = 0.002), whilst the rate of evolution to AML was similar (1.8 vs. 1.3%). By multivariable analysis, older age remained the main factor associated with mortality [HR 1.64 (95% CI 1.5-1.7), p < 0.001], followed by disease severity by Camitta classification [HR 2.24 (95% CI 1.6-3.1) for severe AA; HR 3.8 (95% CI 2.4-6) for very severe AA], and male gender [1.45 (95% CI 1.1-1.8), p < 0.001]. In this large study, elderly AA was associated with inferior outcome even in the TPO-RA era, highlighting the need for further optimization of clinical management.

P-2317. Risk Factors Associated with post-Hematopoietic Stem Cell Transplant Mortality: Two-Year Cohort in a Public Hospital in Perú

Abstract Background In Latin America, Hematopoietic Stem Cell Transplants have experienced significant growth in recent years, both in terms of quantity and quality. Specialized hospitals and high-level medical centers have been established in several countries, including Perú, to carry out these procedures. The availability of compatible donors, the experience of the medical team, the condition of the recipient, the stage of the disease, the resources available for monitoring and surveillance of transplant complications are some of the factors involved in the success of the transplant. This study aims to describe the characteristics and factors associated with mortality in hematopoietic transplant recipients in patients post hematopoietic stem cell transplant attended at a hospital in Peru sociodemographic characteristics Methods Retrospective cohort study, conducted at a hospital in Peru between April and May 2024. We included all patients who underwent hematopoietic stem cell transplant between 2017 and 2022. We evaluated death at one hundred days of follow-up and at two years. Survival at 100 days post transplant Results We evaluated 342 medical records, median age 23 years, 53.5% were women. The most common diagnosis for the transplant was leukemia 83.6%. Mortality in the first 100 days post TPH was 8.2%, and at two years was 30.4%. In the multivariate model and at one hundred days, sepsis HRa: 24.72 (7.95 to 76.85) was associated with death and engraftment to survival HRa: 0.26 (0.07 to 0.93). Regarding mortality at two years, haploidentical transplant HRa:1.92 (1.20 to 3.08), sepsis HRa: 5.36 (2.98 to 9.63), and disease relapse HRa: 4.32 (2.80 to 6.66) were associated with death and engraftment to survival HRa: 0.12 (0.06 to 0.25). 2-year post-transplant survival Conclusion Sepsis was the primary risk factor associated with death in the first one hundred days post-transplant. At two years of follow-up, disease relapse and sepsis were the risk factors for death. Hematopoietic stem cell transplant in Peru is performed in few specialized centers and this initial report identifies the need for further interventions to reduce the risk of infection. Disclosures All Authors: No reported disclosures

Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial)

IntroductionGraft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30–70% of patients (representing 800 new patients per year in the UK). The risk is higher...

Genital graft versus host disease in women after allogeneic hematopoietic stem cell transplantation - a single center experience.

Chronic Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), affecting the female genital tract in 25-66% of the patients. This condition, referred to as Genital GVHD is an underdiagnosed gynecologic comorbidity, that can significantly impair quality of life. We aimed to describe the prevalence and management of genital GVHD following HSCT. This retrospective analysis included women who underwent allogeneic HSCT at a single Bone Marrow Transplantation Unit between 2015 and 2020 and were evaluated at a specialized Vulvo-Vaginal Clinic. Diagnosis and severity of genital GVHD were based on the recommendations by the National Institute of Health (NIH), therapeutic options included topical treatments and surgical interventions. Of the thirty-six patients evaluated, 19.4% were diagnosed with genital GVHD. Patients with genital GVHD were older than those with no-genital GVHD (58.42 vs 47.48years, p = 0.02), and most of them had concurrent multi-organ chronic GVHD (85.71%). Genital GVHD was mostly symptomatic in our cohort (71.42%), clinical findings at the time of diagnosis corresponded with NIH grade 3 (severe disease) in 57.1% of cases. Topical treatments were initiated for all patients with genital GVHD, one required surgical intervention. Genitourinary syndrome of menopause (GSM) was diagnosed among 100% of patients with genital GVHD and among 58.62% of patients without genital GVHD (p = 0.08). In the genital GVHD group, adherence to clinical follow up was limited (43.85%). Genital GVHD should be considered as part of chronic GVHD evaluation after allogeneic HSCT. It is associated with advanced age and the presence of chronic systemic GVHD. Impaired quality of life and limited follow-up within this population emphasize the need for increased awareness and early evaluations.

New Onset Diabetes After Organ Transplantation: Risk Factors, Treatment, and Consequences

New onset diabetes mellitus after organ transplantation (NODAT) is a frequent and serious complication of solid organ transplantation. It significantly impacts graft function, patient survival, and quality of life. NODAT is diagnosed based on the criteria for type 2 diabetes, with the oral glucose tolerance test (OGTT) serving as the gold standard for diagnosis. The development of NODAT is influenced by a range of risk factors, which are classified into modifiable and non-modifiable categories. Post-transplant, regular glycemic monitoring at specific intervals is essential for timely diagnosis and initiation of therapy. Early intervention can help prevent or delay the onset of diabetes-related complications. The treatment strategy for NODAT involves lifestyle modifications and pharmacological interventions. These include medications such as metformin, sulfonylureas, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and insulin. Adjusting immunosuppressive therapy—either by reducing dosages or substituting drugs with lower diabetogenic potential—is a common preventative and therapeutic measure. However, this must be performed cautiously to avoid acute graft rejection, which poses a greater risk to the patient compared to NODAT itself. In addition to managing diabetes, addressing comorbidities such as hypertension and dyslipidemia is crucial, as they elevate the risk of cardiovascular events and mortality. Patients with NODAT are also prone to developing common diabetes-related complications, including diabetic nephropathy, neuropathy, retinopathy, and peripheral vascular disease. Therefore, regular follow-ups and appropriate treatment are vital to maintaining quality of life and improving long-term outcomes.

GRINA alleviates hepatic ischemia‒reperfusion injury-induced apoptosis and ER-phagy by enhancing HRD1-mediated ATF6 ubiquitination.

Hepatic ischemia‒reperfusion injury (HIRI) is a critical complication of liver surgery and transplantation that contributes significantly to severe organ failure. GRINA, a calcium-regulating endoplasmic reticulum (ER) protein, plays an essential role in controlling the unfolded protein response; however, its role in HIRI remains unclear. The aim of this study was to investigate the function of GRINA in HIRI and explore its potential as a therapeutic target. Liver tissues from patients undergoing hepatectomy, alongside a mouse model of partial HIRI, were used to assess GRINA expression levels. Hepatocyte-specific Grina knockout and transgenic mouse models were generated to explore the effects of GRINA on HIRI. Key markers of inflammation, apoptosis, ER stress, and autophagy were evaluated via real-time PCR, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. RNA sequencing, mass spectrometry, coimmunoprecipitation and ubiquitination assays were used to elucidate the underlying molecular mechanisms. GRINA expression was markedly reduced in hepatocytes from both patients and mice with HIRI, and its expression was inversely correlated with the severity of liver damage. Hepatocyte-specific Grina overexpression mitigated liver injury, the inflammatory response, and hepatocyte apoptosis following HIRI, whereas GRINA deficiency exacerbated these outcomes. Mechanistically, GRINA interacted directly with ATF6 and recruited HRD1 to form a multiprotein complex that catalyzed ATF6 polyubiquitination, thereby promoting its degradation. This process suppressed ER autophagy (ER-phagy), providing cellular protection following HIRI. The inhibition of ATF6 degradation attenuated the protective effects of GRINA in HIRI. Our study highlights the critical role of the GRINA-HRD1-ATF6 complex in regulating ER stress and autophagy during HIRI. These findings provide new insights into therapeutic strategies to alleviate HIRI. HIRI represents a multifaceted pathophysiological challenge commonly encountered during liver surgeries, yet its underlying molecular mechanisms remain inadequately understood. In this study, we revealed a significant negative correlation between GRINA levels and the severity of liver damage in patients with HIRI. Our findings demonstrate that GRINA alleviates endoplasmic reticulum stress by enhancing HRD1-mediated ubiquitination of ATF6, thereby maintaining calcium homeostasis and inhibiting ER-phagy. This study provides novel insights into the role of GRINA in protecting liver cells under HIRI, offering fresh perspectives for clinical prevention and management strategies for HIRI.

Telomere shortening in donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation: a case report.

Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes. Donor origin of APL cells was validated by conventional karyotyping, florescence in situ hybridization, and single-nucleotide polymorphisms-based chimerism analysis. Targeted sequencing of both the donor and the recipient demonstrated newly-acquired PML::RARA fusion only in the recipient's cells after transplantation, without additional genetic abnormalities. The telomere length was measured at multiple timepoints before and after transplantation. The analysis revealed markedly shortened telomere length at APL onset, which reflect both stem cell expansion following transplantation and expansion of APL cells. Our first-ever report of telomere dynamics in DCL cases provides evidence for the involvement of telomere attrition in DCL pathogenesis.

The relationship between surgical difficulty and postoperative complications in kidney transplantation: establishment of a preoperative prediction model.

Introduction This study aims to investigate the relationship between surgical difficulty and postoperative complications in kidney transplantation, as well as to develop a preoperative prediction model for assessing surgical difficulty. Methods This is a prospective cohort included 122 kidney transplant adult recipients. The subjective score for operative difficulty, ranging from 1 to 3 points, served as the quantitative measure of surgical difficulty. Analysis of Variance (ANOVA) and Chi-square tests were employed to investigate the differences in postoperative complications. Additionally, Pearson and Spearman correlation analyses were conducted to assess the relationship between preoperative data and surgical difficulty scores, while multiple linear regression analysis was utilized to develop a prediction model. Results With the increase of surgical difficulty, the incidence and severity of postoperative complications of kidney transplant recipients increased significantly (1 vs 2, P=0.009; 1 vs 3, P=0.004; 2 vs 3, P=0.004). The incidence of delayed graft function (DGF) and graft loss was relatively high(1 vs 2, P<0.001; 1 vs 3, P<0.001; 2 vs 3, P=0.131). The source of donor kidney, number of arteries after donor kidney trimming, end resistance index of in vitro perfusion, vascular anastomosis mode of recipient, BMI, and calcification of the vessels to be anastomosed were influencing factors of surgical difficulty. The results of linear regression analysis showed that the difficulty of surgery =0.30 (donated by relatives) +0.48× the number of arteries +0.58× end resistance index of isolated perfusion +0.24× the mode of arterial anastomosis+0.02×BMI+0.17 (calcification of the vessel). Conclusion Higher levels of difficulty in kidney transplantation are associated with increased incidence and severity of postoperative complications, as well as prolonged recovery times. Concurrently, we developed a predictive model to quantify the difficulty of kidney transplantation and validated its accuracy.

Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol. A multicenter, retrospective chart review of adult acute leukemia patients who received ≥1 dose of GO or InO at DFCI/some of the Harvard Cancer Centers during 4-year period (9/1/2017-9/1/2021). Acute promyelocytic leukemia patients and post-GO or InO HSCT-recipients (100-day follow-up period) were excluded. Descriptive summaries are provided, direct comparisons were made using Student T-test (continuous variables) and Fisher's exact test (categorical variables). In our population (N = 82), 87.8% received ursodiol and 12.2% did not. There were no significant differences in baseline to peak hepatic labs. The No-Ursodiol Group had higher incidence of Grade 3 aspartate aminotransferase (AST) transaminitis vs. the Ursodiol Group (60% vs. 20.8%; p = 0.015), and a trend towards shorter mean time to Grade 3 AST transaminitis (18.5 vs. 23.8 days; p = 0.30). Moreover, 4.2% of Ursodiol Group developed SOS/VOD vs. 0% in the No-Ursodiol Group (NS). Three patients developed SOS/VOD: 2 received GO, 1 received InO, and 2 were alive by the end of the follow-up period. In our cohort, ursodiol prophylaxis in adults receiving GO/InO is not associated with lower incidences of hepatotoxicity, SOS/VOD, or time to Grade 3 AST transaminitis, but is associated with decreased incidence of AST elevations.

Incidence, risk factors, and outcomes of transplant-associated thrombotic microangiopathy in pediatric patients after allogeneic hematopoietic cell transplantation: a single-institution prospective study.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication in hematopoietic cell transplantation (HCT). Given the rarity of prospective pediatric studies on TA-TMA, this study aimed to evaluate the incidence, survival outcomes, and risk factors for predicting early the development of TA-TMA in a pediatric population following allogeneic HCT. We conducted a prospective analysis of 173 pediatric patients to evaluate the incidence, survival outcome, and risk factors of TA-TMA. The cumulative incidence of TA-TMA at one-year post-HCT was 4.7% (95% CI, 2.2-8.6%). Patients with TA-TMA showed significantly poorer 1-year overall survival (OS) rate, 50.0% ± 17.7% compared to 85.4% ± 2.8% in those without TA-TMA (p = 0.008). Additionally, the non-relapse mortality (NRM) rate was higher in the TA-TMA group at 12.5% (95% CI, 3.7-55.8%) versus 7.0% (95% CI, 2.8-10.1%) (p = 0.598). A urine protein/creatinine ratio ≥ 1 mg/mg on day 30 post-HCT was significantly associated with TA-TMA occurrence (adjusted HR, 9.5; [95% CI], 1.28-70.39; p = 0.028). This study showed the significantly unfavorable clinical outcomes associated with TA-TMA in pediatric patients and emphasized the importance of early identification of patients at risk. Further research is needed to explore additional strategies for early detection and intervention to improve outcomes.

Primary Graft Dysfunction after Heart Transplantation: Current Evidence and Implications for Clinical Practice.

This review summarizes the current literature on primary graft dysfunction highlighting the current definition, reviewing epidemiology, and describing donor, recipient, and perioperative risk factors in the contemporary era. PGD, in its most severe form, complicates 8% of heart transplants and portends a 1-year mortality of close to 40%. PGD is multifactorial and heterogeneous with contributions from donor and recipient risk as well as organ recovery and preservation modalities. Biomarkers may enhance risk stratification and lend insight into the underlying mechanism of PGD. Temperature-controlled storage and hypothermic oxygenation perfusion systems, in particular, may have significant potential to mitigate PGD risk. PGD is a devastating early complication of heart transplantation that is both complex and multifactorial. Despite its incidence and impact the underlying biology of PGD remains poorly understood. Future studies mechanistic studies are needed to address the underlying pathophysiology of PGD to develop targeted prophylactic and/or therapeutic interventions.

BK Polyomavirus-associated nephropathy - diagnostic and treatment standard.

BK polyomavirus (BKPyV) is recognised as a significant viral complication of kidney transplantation. Prompt immunosuppression reduction reduces early graft failure rates due to BK polyomavirus-associated nephropathy (BKPyVAN), however modulation of immunosuppression can lead to acute rejection. Medium-to-long term graft outcomes are negatively impacted by BKPyVAN, likely due to a combination of virus-induced graft damage and host immune responses against graft alloantigens potentiated by immunosuppression reduction. Kidney biopsy remains the gold-standard diagnostic test, however false negative findings are common due to the focal nature of BKPyVAN. BKPyV DNAemia, as measured by quantitative polymerase chain reaction (qPCR), is established as a screening test but there is at present no (inter)national standardisation of these assays to allow collation and comparison of data between centres. Randomised controlled trials are lacking both in terms of optimal immunosuppression reduction strategies, and for the medications variably used to attempt treatment in clinical practice. Much of the fundamental biology of BKPyV is not yet understood, and further elucidation is required to promote rational direct-acting antiviral drug design. Insights into the role of adaptive immunity in control of BKPyV have informed the design of novel treatments such as adoptive immunotherapies and neutralizing antibodies which require evaluation in clinical studies. Here, we review the current standards of diagnosis and treatment of BKPyVAN and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management.