Early Post Transplant Research Articles

P.238: Nephrotic syndrome early post kidney transplantation - rare manifestation of acute rejection.

P.238: Nephrotic syndrome early post kidney transplantation - rare manifestation of acute rejection.

Outcomes of Early Thrombotic Microangiopathy in Renal Transplantation.

Alternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post-transplant, coupled with a lack of follow-up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4months post-transplantation, and explore any differences in follow-up surveillance biopsies compared to a non-TMA group. This is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4months post-transplantation were compared to a propensity matched non-TMA group. Thirty-one patients developed TMA within 4months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four-month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non-TMA group. However, at 1year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non-TMA, p=0.083); however, death censored graft survival was significantly lower in the TMA group (p<0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4months and at 1year as compared to the non-TMA group. Early onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.

#1274 Post kidney transplant parvovirus disease presenting as refractory anemia—case series of 21 patients

Abstract Background and Aims Kidney transplant recipients (KTRs) are susceptible to a wide range of infections, one of which includes Parvovirus B19 (PVB19). It usually presents in the first year after transplant, with anemia and causes increased morbidity and risk of graft dysfunction. Method Charts of patients undergoing kidney transplant between May 2013 and March 2022 were reviewed. 21 patients had PVB19. Their clinical presentation, laboratory parameters and outcome was studied. The diagnosis of PVB19 was established by PVB19 polymerase chain reaction (PCR) and by bone marrow examination(BME) in 6 patients. Results Prevalence of PVB19 disease was 1.9% (21/1164) with a median time to onset was 39 days post-transplantation. Clinical presentation included fever, generalized weakness, dyspnea, and myalgia in 47%, 76%, 23%, and 33% of patients respectively. Anemia, leukopenia, and thrombocytopenia were present in 100%, 14%, and 9.5% of patients respectively. Graft dysfunction was observed in 61.9% (13/21) patients. 20/21 (95%) patients had a positive PVB19 PCR and one patient had a typical viral inclusion on BME. Immunosuppression especially antiproliferative was reduced in all patients. 8 patients received IVIG, 8 received packed cell blood transfusion and 7 received Erythropoietin therapy. All patients recovered with median time to normalization of hemoglobin was 30 days. One patient had graft loss secondary to non-responsive graft rejection. Conclusion PVB19 is a rare but clinically significant cause of refractory anemia during the early post-transplantation. Any kidney transplant patient in first 4 months who has unexplained normocytic normochromic refractory anemia with or without graft dysfunction should be screened for PVB19 by DNA PCR or BME to rule out PVB19 infection. The use of PCR for diagnosis and reduction in immunosuppressants particularly antiproliferative drugs is the mainstay of treatment.

#1731 Clinico-epidemiological characteristics of early versus late onset cytomegalovirus disease among renal transplant recipients: two decade experience

Abstract Background and Aims The epidemiology of the Cytomegalo virus (CMV) disease among renal transplant recipients has changed with the advent of effective antiviral prophylaxis usually occurs in the later part of the post transplant period. To study the difference between CMV infections occurring in early versus late post renal transplant period with respect to nature of immunosuppressive medications (induction agents, maintenance agents and heightening of immunosuppression), type of CMV infection and occurrence of biopsy proven rejection post CMV infection. Method A single centre retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between 1st January, 2002 and 31st December, 2021. CMV disease was classified as early or late depending on detection before or after 90 days post transplant. The differences in clinical presentation between early and late onset CMV disease, use of immunosuppression, and the impact on graft outcomes were studied. Results Total number of recipients with CMV disease was 156 (7.2%) out of total 2164 renal transplant recipients. Twenty-five (16%) patients had early CMV while one hundred and thirty one (84%) had late CMV. The two groups did not differ with respect to induction or use of maintenance immunosuppressive agents. Proportion of CMV syndrome was more among early CMV group (56.0% vs 26.7%, p = 0.01) while tissue invasive disease was more frequent among late CMV group (44.0% vs. 73.3%, p = 0.01). Diarrhoea was more frequent in late (63.4%) versus early CMV (36%) (p = 0.01). Graft loss occurred in 4.0% of early and 25.2% of late CMV cases (p = 0.03). However, both groups did not differ with respect to occurrence of biopsy proven rejection post infection. Conclusion Early CMV presents more frequently as CMV syndrome while late CMV usually manifests as tissue invasive disease. Graft loss is more common in patients with late onset disease.

Mucormycosis-Associated Colon Perforation in the Early Postrenal Transplant Period

The incidence of colon perforation in the posttransplant period is 1.3% based on various single-center studies. We report the case of a 32-year-old male, a known case of chronic kidney disease and end-stage renal disease who received a live-related ABO-compatible transplant. The patient was started on tacrolimus, mycophenolate mofetil, and steroids; no induction was given. The patient had a delayed graft function, and his creatinine was persistently high. Hence, a biopsy was done on postoperative day 4, which revealed an acute tubular injury with features of calcineurin inhibitor toxicity. His tacrolimus dose was reduced and his output improved until day 13, after which his renal function worsened. The repeat tacrolimus level was low. Hence, the patient was started on pulse steroids and discharged after the patient improved symptomatically (discharge creatinine: 2.1). The patient was readmitted 3 days after discharge with severe abdominal pain. The patient’s blood pressure was 90/30 mmHg; he was drowsy and tachypneic. His abdomen was distended. Computed tomography of the abdomen revealed pneumoperitoneum, and the patient was subjected to an explorative laparotomy. There was colonic perforation. The peritoneum and colon revealed multiple punched-out lesions and a right hemicolectomy was done. A biopsy revealed suppurative inflammation involving all three layers with multiple giant cells, and tissue staining revealed ribbon-like aseptate hyphae with 90° angulation suggestive of mucormycosis. The patient expired in the immediate postoperative period. The final diagnosis of mucormycosis-associated colon perforation was made. Only one such case has been reported previously.

Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.

The Burden and Impact of Early Post-transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005-2021.

Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score-weighted sensitivity, and subgroup analyses were performed. Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%-1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31-0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21-8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92-55.5; subdistribution aHR, 7.15; 95% CI, 0.95-53.7). A similar trend was seen in the subgroup and sensitivity analyses. MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.

Prognostic value of ultrasound in early arterial complications post liver transplant.

Liver transplantation is the primary therapeutic intervention for end-stage liver disease. However, vascular complications, particularly those involving the hepatic artery, pose significant risks to patients. The clinical manifestations associated with early arterial complications following liver transplantation are often nonspecific. Without timely intervention, these complications can result in graft failure or patient mortality. Therefore, early diagnosis and the formulation of an optimal treatment plan are imperative. Ultrasound examination remains the predominant imaging modality for detecting complications post liver transplantation. This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these conditions. Overall, ultrasound offers the advantages of convenience, safety, effectiveness, and non-invasiveness. It enables real-time, dynamic, and precise evaluation, making it the preferred diagnostic method for post-liver transplantation assessments.

Analysis of high-risk factors for early pulmonary bacterial infection after lung transplantation and their correlation with long-term mortality.

To investigate the high-risk factors for early pulmonary bacterial infection following lung transplantation and their association with long-term mortality. A retrospective analysis was conducted on 142 lung transplant recipients treated at Wuxi People's Hospital between January 2018 and July 2022. After applying predefined inclusion and exclusion criteria, 111 cases were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for early pulmonary infection post-transplantation. Additionally, univariate and multivariate Cox regression analyses were used to identify independent prognostic factors affecting one-year survival post-transplantation. Univariate analysis identified age, bacterial infection in donor lungs, and operation duration as risk factors for early pulmonary infection (all P < 0.05). Multivariate analysis was confirmatory for these as independent risk factors (all P < 0.05). Univariate analysis also showed that intraoperative blood loss and oxygenation index impacted one-year survival (P < 0.05). Multivariate analysis was confirmatory for these as independent risk factors (P < 0.05). Early pulmonary bacterial infection was not found to be an independent factor affecting 1-year survival. However, substantial intraoperative blood loss and a reduced oxygenation index were identified as independent risk factors associated with increased mortality within 1 year post-transplantation.

Identification and surveillance of rare relapse-initiating stem cells during complete remission after transplantation

AbstractRelapse after complete remission (CR) remains the main cause of mortality after allogeneic stem cell transplantation for hematological malignancies and, therefore, improved biomarkers for early prediction of relapse remains a critical goal toward development and assessment of preemptive relapse treatment. Because the significance of cancer stem cells as a source of relapses remains unclear, we investigated whether mutational screening for persistence of rare cancer stem cells would enhance measurable residual disease (MRD) and early relapse prediction after transplantation. In a retrospective study of patients who relapsed and patients who achieved continuous-CR with myelodysplastic syndromes and related myeloid malignancies, combined flow cytometric cell sorting and mutational screening for persistence of rare relapse-initiating stem cells was performed in the bone marrow at multiple CR time points after transplantation. In 25 CR samples from 15 patients that later relapsed, only 9 samples were MRD-positive in mononuclear cells (MNCs) whereas flowcytometric-sorted hematopoietic stem and progenitor cells (HSPCs) were MRD-positive in all samples, and always with a higher variant allele frequency than in MNCs (mean, 97-fold). MRD-positivity in HSPCs preceded MNCs in multiple sequential samples, in some cases preceding relapse by >2 years. In contrast, in 13 patients in long-term continuous-CR, HSPCs remained MRD-negative. Enhanced MRD sensitivity was also observed in total CD34+ cells, but HSPCs were always more clonally involved (mean, 8-fold). In conclusion, identification of relapse-initiating cancer stem cells and mutational MRD screening for their persistence consistently enhances MRD sensitivity and earlier prediction of relapse after allogeneic stem cell transplantation.

106.6: Spatial transcriptomic analysis on the liver of pig-to-NHP islet transplantation recipient reveals increased adipogenesis and non-alcoholic fatty liver disease pathway in early post-transplantation

106.6: Spatial transcriptomic analysis on the liver of pig-to-NHP islet transplantation recipient reveals increased adipogenesis and non-alcoholic fatty liver disease pathway in early post-transplantation

Thrombolysis for acute myocardial infarction in early post-renal transplant period: A case report

Cardiovascular disease is a major contributor to morbidity and has become the leading cause of death among renal transplant patients. This paper presents a case of acute myocardial infarction occurring three weeks after a renal transplant. A 45-year-old male recipient experienced acute chest pain, hypotension, and atrial fibrillation, leading to a diagnosis of inferior-posterior wall myocardial infarction. Thrombolysis with Tenectaplase was administered, resulting in the development of a perinephric hematoma six hours later. The patient underwent transfusions and pigtail drainage of the hematoma. Following hematoma resolution, the pigtail catheter was removed, and the patient was started on dual anti-platelets. Upon discharge, the patient exhibited stable renal function. In conclusion, thrombolysis in the early post-transplant period poses significant risks. This case highlights the use of thrombolytic therapy during this period and the successful management of associated complications.

Initial dosage optimisation of cyclosporine in Chinese paediatric patients undergoing allogeneic haematopoietic stem cell transplantation based on population pharmacokinetics: a retrospective study

ObjectiveImproved understanding of cyclosporine A (CsA) pharmacokinetics in children undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) is crucial for effective prevention of acute graft-versus-host disease and medication safety. The aim...

Circulating “Neutrophils extra-cellular traps” during the early post-renal transplant period and correlation with graft dysfunction and rejection

BackgroundNeutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI. MethodsProspectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome. ResultsCirculating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01–0.19) to 0.51 (0.22–0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12–0.27) to 0.38 (0.19–0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18–0.72) and 0.35 (0.26–0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13–0.31) to 0.38 (0.28–1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74–12.56) μM to 17.37 (9.11–22.25) μM; p = 0.03 in group-A, and 8.7 (6.04–10.30) μM to 14.66 (13.39–21.63) μM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64–13.90) μM and 11.11 (9.15–17.54) μM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both. ConclusionCirculating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.

Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients.

Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI. We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.

Intestinal Permeability in Patients Early after Kidney Transplantation Treated with Two Different Formulations of Once-Daily Tacrolimus.

Adequate tacrolimus blood exposure is crucial in the early post-renal transplant period and a gut epithelial barrier integrity may play a role. We prospectively investigated several markers of intestinal permeability in recent kidney transplant recipients (KTRs) treated with different tacrolimus extended-release formulations. Within each of the 49 KTR pairs that received grafts from the same donor, an early randomized conversion was performed from twice-daily (Prograf) to once-daily tacrolimus formulation: Advagraf or Envarsus. Plasma zonulin, calprotectin, circulating lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (FABP-2), and CD-14 levels were measured. There was no difference in the recipient age, dialysis vintage, BMI, and residual diuresis between Advagraf and Envarsus groups. FABP-2 and LPS levels were significantly associated with tacrolimus trough level, 3-h level, and area under the curve (AUC) in the Envarsus but not in the Advagraf group. AUC was independently increased by LPS and decreased by age, FABP-2 concentration, and the use of Envarsus formulation as compared with Advagraf. Functional changes of gastrointestinal tract in patients treated with Envarsus may influence intestinal tacrolimus absorption to a greater extent than in Advagraf-treated KTRs and may lead to inadequate variability of tacrolimus exposure early after kidney transplantation.

Single-cell transcriptomics of human-skin-equivalent organoids

Several methods for generating human-skin-equivalent (HSE) organoid cultures are in use to study skin biology; however, few studies thoroughly characterize these systems. To fill this gap, we use single-cell transcriptomics to compare invitro HSEs, xenograft HSEs, and invivo epidermis. By combining differential gene expression, pseudotime analyses, and spatial localization, we reconstruct HSE keratinocyte differentiation trajectories that recapitulate known invivo epidermal differentiation pathways and show that HSEs contain major invivo cellular states. However, HSEs also develop unique keratinocyte states, an expanded basal stem cell program, and disrupted terminal differentiation. Cell-cell communication modeling shows aberrant epithelial-to-mesenchymal transition (EMT)-associated signaling pathways that alter upon epidermal growth factor (EGF) supplementation. Last, xenograft HSEs at early time points post transplantation significantly rescue many invitro deficits while undergoing a hypoxic response that drives an alternative differentiation lineage. This study highlights the strengths and limitations of organoid cultures and identifies areas for potential innovation.

Dynamic comparison of early immune reactions and immune cell reconstitution after umbilical cord blood transplantation and peripheral blood stem cell transplantation.

Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and non-malignant refractory hematological diseases. However, the differences in the immune cell reconstitution and the immune reactions during initial stages post-transplantation are not well established between UCBT and PBSCT. Therefore, in this study, we analyzed the differences in the immune reactions during the early stages (days 7-100 post-transplantation) such as pre-engraftment syndrome (PES), engraftment syndrome (ES), and acute graft-versus-host disease (aGVHD) and the immune cell reconstitution between the UCBT and the PBSCT group of patients. We enrolled a cohort of patients that underwent UCBT or PBSCT and healthy controls (n=25 each) and evaluated their peripheral blood mononuclear cell (PBMC) samples and plasma cytokine (IL-10 and GM-CSF) levels using flow cytometry and ELISA, respectively. Our results showed that the incidences of early immune reactions such as PES, ES, and aGVHD were significantly higher in the UCBT group compared to the PBSCT group. Furthermore, in comparison with the PBSCT group, the UCBT group showed higher proportion and numbers of naïve CD4+ T cells, lower proportion and numbers of Tregs, higher proportion of CD8+ T cells with increased activity, and higher proportion of mature CD56dim CD16+ NK cells during the early stages post-transplantation. Moreover, the plasma levels of GM-CSF were significantly higher in the UCBT group compared to the PBSCT group in the third week after transplantation. Overall, our findings demonstrated significant differences in the post-transplantation immune cell reconstitution between the UCBT and the PBSCT group of patients. These characteristics were associated with significant differences between the UCBT and the PBSCT groups regarding the incidences of immune reactions during the early stages post transplantation.

Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). To date, few studies have examined risk factors for AKI at engraftment, or the relationship between AKI and clinical outcomes. This study examined the incidence and risk factors for periengraftment AKI, as well as the association between AKI and overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of adult patients undergoing reduced-intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Periengraftment (day 0 to day 30) AKI incidence and severity were defined using modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Factors associated with periengraftment AKI risk were examined using Cox regression analysis. The impact of periengraftment AKI on OS and NRM (defined as death without recurrent disease after HCT), was evaluated using Cox regression and the Fine and Gray competing risks model, respectively. Kidney recovery, defined as a return of serum creatinine (SCr) to within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 post-HCT. Periengraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days (interquartile range, 4 to 30 days) post-transplantation. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.20 to 2.03; P < .001), fludarabine/melphalan conditioning (HR, 1.35, 95% CI, 1.01 to 1.81; P=.05, compared to fludarabine/busulfan and fludarabine, cyclophosphamide, and total body irradiation), HCT Comorbidity Index ≥4 (HR, 1.43; 95% CI, 1.14 to 1.79; P=.002), albumin <3.4 g/dL (HR, 2.04; 95% CI, 1.33 to 3.12; P=.001), hemoglobin ≤12 (HR, 1.96; 95% CI, 1.38 to 2.78; P < .001), supratherapeutic tacrolimus (HR, 1.45; 95% CI, 1.07 to 1.95; P=.02), and baseline SCr >1.1 mg/dL (HR, 1.87; 95% CI, 1.48 to 2.35; P < .001). Periengraftment AKI was associated with worse OS (HR, 1.40; 95% CI, 1.16 to 1.71; P < .001) and NRM (subdistribution HR, 2.10; 95% CI, 1.52 to 2.89; P < .001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, stage 2, and stage 3 AKI without KRT, respectively, and 4 of 16 patients (25%) were liberated from KRT. Periengraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for periengraftment AKI. Its association with worse OS and NRM underscores the importance of timely recognition and management.

Once-Daily Foscarnet Is Effective for Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Transplantation

Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients.