Post Transplant Research Articles

Prostaglandin E1 administration post liver transplantation and renal outcomes: A retrospective single center experience.

Prostaglandin E1 (PGE1), or alprostadil, is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation (LT). However, the benefits of PGE1 on renal function after LT have not yet been well described. To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant. This retrospective study included all patients who underwent liver or liver-kidney transplant at our institution from January, 2011 to December, 2021. Patients were classified based on whether they received PGE1. PGE1 was administered post-LT to those with transaminases > 1000 U/L in the immediate postoperative period. Demographics, post-LT treatments and/or complications, renal function, and survival were analyzed. Multivariable logistic regression analysis was performed, and a two-tailed P value < 0.05 was considered statistically significant. A total of 145 patients underwent LT, with 44 (30%) receiving PGE1. Baseline patient characteristics were comparable, except the PGE1 group had significantly higher aspartate aminotransferase (AST) (1961.9 U/L ± 1862.3 U/L vs 878 U/L ± 741.4 U/L, P = 0.000), alanine aminotransferase (1070.6 U/L ± 895 U/L vs 547.7 U/L ± 410 U/L, P = 0.000), international normalized ratio on post-LT day 1 (2 ± 0.74 vs 1.8 ± 0.4, P = 0.03), a longer intensive care unit stay (8.1 days ± 11.8 days vs 3.8 days ± 4.6 days, P = 0.003), more vasopressor use (55.53 hours ± 111 hours vs 16.33 hours ± 26.3 hours, P = 0.002), and higher immediate postoperative complications (18.6% vs 4.9%, P = 0.04). The PGE1 group also had a significantly higher 90-day readmission rate (29.6% vs 13.1%, P = 0.02) and lower 1-year liver graft survival (87.5% vs 98.9%, P = 0.005). However, 30-day readmission (31.6% vs 27.4%, P = 0.64), LT complications (hepatic artery thrombosis, biliary complications, rejection of liver graft, cardiomyopathy), 1-year patient survival (96.9% vs 97.8%, P = 0.77), overall liver graft survival, and overall patient survival were similar between the two groups (95.4% vs 93.9%, P = 0.74 and 88.4% vs 86.9%, P = 0.81 respectively). Although the PGE1 group had a significantly lower glomerular filtration rate (eGFR) on post-LT day 7 (46.3 mL/minute ± 26.7 mL/minute vs 62.5 mL/minute ± 34 mL/minute, P = 0.009), the eventual need for renal replacement therapy (13.6% vs 5.9%, P = 0.09), the number of dialysis sessions (0.91 vs 0.27, P = 0.13), and eGFR at 1-month (37.2 mL/minute ± 35.9 mL/minute vs 42 mL/minute ± 36.9 mL/minute, P = 0.49), 6-months (54.8 mL/minute ± 21.6 mL/minute vs 62 mL/minute ± 21.4 mL/minute, P = 0.09), and 12-months (63.7 mL/minute ± 20.7 mL/minute vs 62.8 mL/minute ± 20.3 mL/minute, P = 0.85) post-LT were similar to those in the non-PGE1 group. In patients who received PGE1 for ischemia-reperfusion injury, despite immediate acute renal injury post-LT, the renal function at 1-month, 6-months, and 12-months post-LT was similar compared to those without ischemia-reperfusion injury. Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.

Fearsome four- Fungal infections in renal transplant recipients

To study the clinical presentation, diagnostic methods, treatment and outcomes of Invasive Aspergillosis Cryptococcal infection, Mucormycosis and Histoplasmosis in renal transplant recipients. : We performed a retrospective analysis of renal transplant recipients with four major fungal infections from January 2000 until December 2022 at a tertiary care centre in Southern India. This study was approved by the institutional ethical committee. We have identified these cases from the electronic records of the microbiology department and renal transplant outpatient clinic. A total of 1970 patients underwent renal transplantation at this institute during study period. A total of 25 patients were diagnosed as having invasive Aspergillosis - 20 patients had pneumonia, three had right maxillary sinusitis, one each had left chronic suppurative otitis media, and skull base osteomyelitis). There were 20 patients with cryptococcal infection of which eight had disseminated infection, seven had meningitis, four had cutaneous cryptococcosis and one had pulmonary cryptococcosis. Mucormycosis was diagnosed in 14 patients, twelve of which had pulmonary mucormycosis, one had oculo-cerebral mucormycosis and one patient had acute invasive fungal maxillarysinusitis. Histoplasmosis was diagnosed in four patients, two of whom had disseminated histoplasmosis and two had cutaneous histoplasmosis. In this study, mortality was highest with mucormycosis (57%) followed by 33.3% with invasive Aspergillosis and 20% with Cryptococci infection. Currently, there is no standard serological test available for the routine identification of invasive fungal infections in patients. Initial cultures may yield negative results due to slow fungal growth and variations in colony appearance. Therefore, it is essential to pursue aggressive sampling methods when fungal infection is suspected. Invasive procedures such as bronchoscopic lavage and abscess aspiration play a crucial role in reaching a diagnosis. In summary, maintaining a high level of suspicion and employing thorough investigations in post-renal transplant recipients are vital for early diagnosis, prompt treatment initiation, prevention of disease spread, and reduction of mortality risk.

Combination Therapy for Cryptosporidiosis in Immunocompromised Patients: A Systematic Review

Cryptosporidium sp. is a pathogen that causes gastroenteritis and may increase mortality and morbidity in immunocompromised patients. Cryptosporidium became widely recognized as a human pathogen. Diarrhea is a common problem in AIDS patients and about 30%–60% of patients in developed countries and 90% in developing countries experience diarrhea. This study was conducted using a systematic review design. Two articles with cohort design and two with case report design were selected based on the eligibility criteria. Three of these studies used a combination of nitazoxanide with azithromycin as an intervention, one in cohort design and two in case report design. One cohort study used a nitazoxanide and fluoroquinolone combination as an intervention. 54 samples participated in this study were post kidney transplantation patients and one sample was with acute lymphoblastic leukemia (ALL). Nitazoxanide and fluoroquinolone combination is a better therapy for cryptosporidiosis in immunocompromised patients compared to nitazoxanide and azithromycin combination. The(OR) for stool clearance was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.65, 95% CI: 0.34, 0.92, P= 0.01), and the OR for diarrhea stopped was significantly lower with nitazoxanide alone compared to that of nitazoxanide and fluoroquinolone (OR: 0.45, 95% CI: 0.21, 0.81, P= 0.004). The OR for stool clearance was lower with nitazoxanide and azithromycin than monotherapy (OR 0.27, 95% CI: 0.01, 5.77), but P=0.24, which means not statistically significant.

Thrombotic complications post liver transplantation: Etiology and management.

Liver transplantation (LT) is the life saving therapeutic option for patients with acute and chronic end stage liver disease. This is a routine procedure with excellent outcomes in terms of patient survival and quality of life post LT. Orthotopic LT (OLT) patients require a critical care as they are prone to variety of post-operative vascular, cardiovascular, biliary, pulmonary and abdominal complications. Thrombotic complications (both arterial and venous) are not uncommon post liver transplant surgery. Such vascular problems lead to increased morbidity and mortality in both donor and graft recipient. Although thromboprophylaxis is recommended in general surgery patients, no such standards exist for liver transplant patients. Drastic advancements of surgical and anesthetic procedures have improvised survival rates of patients post OLT. Despite these, haemostatic imbalance leading to thrombotic events post OLT cause significant graft loss and morbidity and even lead to patient's death. Thus it is extremely important to understand pathophysiology of thrombosis in LT patients and shorten the timing of its diagnosis to avoid morbidity and mortality in both donor and graft recipient. Present review summarizes the current knowledge of vascular complications associated with LT to highlight their impact on short and long-term morbidity and mortality post LT. Also, present report discusses the lacunae existing in the literature regarding the risk factors leading to arterial and venous thrombosis in LT patients.

Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation

IntroductionAcute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.MethodsTo evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).ResultsThe median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).ConclusionsThis retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.

Effects of Tobacco Smoking on Post-Liver-Transplant Outcomes

Background/Objectives: Our study examined 5-year patient and graft survival outcomes among non-smokers, former smokers, and active smokers at the time of liver transplantation (LT) and immediate post-operative complications and short-term outcomes following LT. Methods: This was a retrospective study that examined all liver transplants occurring at Cleveland Clinic Main Campus between January 2015–October 2022. Kaplan–Meier curves examined survival outcomes, and Cox’s multivariate regression analysis was performed. Results: Over the 5-year period, patient survival did not differ statistically between patient groups (all p-values &gt;0.05). However, graft survival was significantly lower in active smokers (p = 0.012). In the multivariate analysis, age (HR = 1.03, 95% CI 1.01–1.05, p = 0.002) and admission to the ICU (HR 1.68, 95% CI 1.13–2.50, p = 0.01) were positively associated with overall mortality. Immediate and short-term complications did not differ statistically between patient groups. Cardiovascular disease (22.5%) was the most common cause of death among all patients. Conclusions: Though our study did not show decreased patient survival outcomes, our findings are in line with previous studies that have shown that pre-transplant smoking is associated with overall reduced graft survival. Combined with the risk for de novo malignancy and cardiovascular events post transplant, smoking cessation before LT should be encouraged to ensure graft longevity.

Prevalence, risk factors, and severity of erectile dysfunction following renal transplantation.

Sexual dysfunction is common among dialysis and transplant patients. Our study evaluated the prevalence, risk factors, and severity of erectile dysfunction (ED) post-transplant in a single center. We conducted a single-centre, observational, non-interventional study of adult male renal graft recipients. Sociodemographic and clinical data were collected, and erectile function was assessed with the International Index of Erectile Function (IIEF) questionnaire. 179 patients transplanted between 1995 and 2021 were enrolled (170 answered the questionnaire). Mild, moderate, and severe ED was noted in 33.5%, 20.6% and 10.6% of cases, respectively. ED prevalence increased with age (42.6% of patients < 40, 47.4% of patients aged 40-60, 78.9% of patients > 60). The total mean IIEF score was 16.32 ± 6.93 (erectile function 19.22 ± 7.9, orgasmic function 6.8 ± 2.9, sexual desire 6.43 ± 2.1, intercourse satisfaction 8.96 ± 3.7, overall satisfaction 6.78 ± 2.6). Age, alcohol consumption, type, time on dialysis pre-transplant, and donor type were significantly associated with erectile dysfunction (p < 0.05). Most patients (93.5%) were treated for comorbidities in addition to immunosuppression. Severe ED was significantly more common among patients taking alpha blockers and non-steroidal anti-inflammatory drugs. Self-reported erectile dysfunction post renal transplantation seems influenced by age, alcohol intake, dialysis history, donor type and certain drugs, but not by comorbidities (hypertension, diabetes, heart disease).

The prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

Effect of Parathyroidectomy After Renal Transplantation on Grafted Kidney Function Within One Year: A Meta-Analysis

Objective: Secondary hyperparathyroidism (sHPT) is a common symptom of chronic kidney disease (CKD), and at the time of transplantation, more than two-thirds of patients with end-stage renal disease have secondary hyperparathyroidism. After kidney transplantation, parathyroid function is normalized in some kidney transplant recipients, but up to 50% of kidney transplant recipients develop tertiary hyperparathyroidism (tHPT) one year after kidney transplantation. The effect of parathyroidectomy on the grafts is currently unclear, so we conducted a meta-analysis of these studies to assess the changes in graft function one year after parathyroidectomy after kidney transplantation to investigate the resection in renal transplant recipients. Methods: A thorough exploration was conducted across Embase, PubMed, Web of Science, and the Cochrane Library databases to gather pertinent literature spanning from January 1, 2000, to December 31, 2023. The search criteria encompassed terms such as "kidney transplantation," "parathyroidectomy," and "hyperparathyroidism." Results: Twelve studies were scrutinized to assess alterations in graft functionality at 1, 3, 6, and 12 months post-parathyroidectomy. The meta-analysis unveiled a notable decline in overall glomerular filtration rate and a concurrent elevation in serum creatinine one year post-parathyroidectomy, signifying an impairment in graft function compared to the preoperative phase. Significant heterogeneity was observed among the studies. Conclusion: Following parathyroidectomy in renal transplant recipients one year post-surgery, calcium and parathyroid hormone levels normalized. Nonetheless, there was evident impairment in graft function and an elevated risk of graft loss. Hence, the safety of parathyroidectomy in patients with secondary hyperparathyroidism post-renal transplantation necessitates meticulous consideration.

Sorafenib as maintenance therapy in FLT3+ acute myeloid leukemia post allogeneic transplantation: a case report.

This case report highlights sorafenib as maintenance therapy postallogeneic hematopoietic stem cell transplantation (allo-HSCT) in a young patient with acute myeloid leukemia (AML) with FMS-like tirosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation. Given the high relapse risk in FLT3-ITD-positive AML, the tyrosine kinase inhibitor sorafenib was administered. Several studies have shown that sorafenib improves survival in younger AML patients when combined with chemotherapy, though side effects can limit use in older patients. Sorafenib is increasingly significant after allo-HSCT maintenance, offering a promising option for high-risk AML cases. In this case, the patient achieved long-term remission with minimal side effects.

Prevalence and Impact of Cytomegalovirus Primary Infection and Reactivation on Graft Function in Post-Renal Transplant Recipients

Prevalence and Impact of Cytomegalovirus Primary Infection and Reactivation on Graft Function in Post-Renal Transplant Recipients

Rapamycin improves satellite cells autophagy and muscle regeneration during hypercapnia.

Both CO2 retention, or hypercapnia, and skeletal muscle dysfunction predict higher mortality in critically ill patients. Mechanistically, muscle injury and reduced myogenesis contribute to critical illness myopathy, and while hypercapnia causes muscle wasting, no research has been conducted on hypercapnia-driven dysfunctional myogenesis in vivo. Autophagy flux regulates myogenesis by supporting muscle stem cell -satellite cell- activation, and previous data suggests that hypercapnia inhibits autophagy. We tested whether hypercapnia worsens satellite cell autophagy flux and myogenic potential, and if autophagy induction reverses these deficits. Satellite cell transplantation and lineage tracing experiments showed that hypercapnia undermines satellite cells activation, replication, and myogenic capacity. Bulk and single cell sequencing analyses indicated that hypercapnia disrupts autophagy, senescence, and other satellite cells programs. Autophagy activation was reduced in hypercapnic cultured myoblasts, and autophagy genetic knockdown phenocopied these changes in vitro. Rapamycin stimulation led to AMPK activation and downregulation of the mTOR pathway, which are both associated with accelerated autophagy flux and cell replication. Moreover, hypercapnic mice receiving rapamycin showed improved satellite cells autophagy flux, activation, replication rate, and post transplantation myogenic capacity. In conclusion, we have shown that hypercapnia interferes with satellite cell activation, autophagy flux and myogenesis, and systemic rapamycin administration improved these outcomes.

GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation - successfully treated by extracorporeal photopheresis.

CAR T-cell therapy is highly effective, but also associated with unique toxicities. Because of the origin of T cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined. Sharing our retrospective experience and a mini-review of the literature, our aim is to better understand the frequency and risk of the potential occurrence of GVHD after CAR T cells, which are most likely underestimated. Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful long-term control of GVHD without causing relapse of the underlying disease. In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility, and the specific CAR construct used.

Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience

Introduction: Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure. Aim: To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients. Methods: Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed. Results: A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV Conclusion: Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.

November 2024 Medical Image of the Month: A Case of Short Telomeres

No abstract available. Article truncated after 150 words. A 50-year-old woman was referred to our institution for further evaluation of her ILD. Her history of present illness began during the COVID-19 pandemic, when she noticed that she had trouble climbing stairs while wearing a mask. She also had a slowly progressive cough which, at first, she attributed to seasonal allergies. Eventually her symptoms prompted pulmonary function testing at an outside institution, which showed moderately severe restriction with a DLco 40% of predicted. Chest x-ray (Figure 1) and chest CT (Figure 2) demonstrated findings of pulmonary fibrosis. The patient worked as an accountant and was a life-long nonsmoker. No concerning exposure history and no history of any medications associated with pulmonary fibrosis. Her family history is remarkable for a brother diagnosed with IPF at age 49, currently status post lung transplant. Her sister and father were both diagnosed with alpha-1-antitrypsin (both died in their 50’s). The patient also reports …

The incidence and clinical significance of monoclonal and oligoclonal protein bands in multiple myeloma patients after BCMA-CAR-T cell therapy: A retrospective study based on LEGEND-2.

The emergence of abnormal protein bands (APBs), also known as oligoclonal protein bands, has been documented in patients with multiple myeloma (MM) post hematopoietic stem cell transplantation. However, the incidence rate and clinical significance of APBs remain contentious. Few studies have explored the occurrence and prognostic implications of APBs in patients with MM treated with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR)-T therapy. In this retrospective study, we examined the frequency, isotypes, and duration of APBs, as well as their correlation with MM disease characteristics, treatment response, clinical outcomes, and immune signature in patients with relapsed/refractory MM who had received LCAR-B38M therapy at the Xi'an site of the phase 1 LEGEND-2 trial. Among 47 patients assessed, 23 (48.9%) developed APBs following CAR-T therapy, with IgG being the most common isotype. The median onset and duration of APBs post-CAR-T infusion were 3.6 and 5.8 months, respectively. Patients with APBs demonstrated significantly improved response to LCAR-B38M therapy, along with longer overall and progression-free survival. Furthermore, those with APBs exhibited enhanced recovery rates of immunoglobulins and higher absolute counts of white blood cells, neutrophils, and lymphocytes post-CAR-T treatment compared to those without APBs. However, no significant differences were observed between the two groups in the percentages of various T-cell subsets and natural killer cells. Overall, the presence of APBs in patients with MM following CAR-T treatment was associated with deeper remission and a more favorable prognosis, suggesting a robust humoral response and subsequent immune reconstitution.

Ibrutinib With Bendamustine and Rituximab for Treatment of Patients With Relapsed/Refractory Aggressive B-Cell Lymphoma.

Therapy for relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aB-NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single-center, single-arm, phase II clinical study, we investigated the efficacy of ibrutinib (560mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28-day cycles in their standard dose, to patients with R/R aB-NHL who were either transplant ineligible in first or second relapse or post-ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty-six patients (54% male, median age 69.7years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, p=0.024). Median overall survival (OS) was 11.6months (95% CI, 7.1-22.3) and median progression-free survival was 5.3months (95% CI, 2.5-7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2months, p<0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow-up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB-NHL.Trial Registration: ClinicalTrials.gov: NCT02747732.

OA06 Echoes of Hope: Navigating Pregnancy post heart transplant in the context of systemic sclerosis

OA06 Echoes of Hope: Navigating Pregnancy post heart transplant in the context of systemic sclerosis

Heart Transplant Rejection in the Setting of Glyphosate Herbicide Exposure; A Case Report

Glyphosate is a common herbicide utilized worldwide with known exposure related toxicities. Numerous adverse effects related to glyphosate exposure have been documented, specifically in non-human models, however literature is lacking on cardiotoxic effects specific to heart transplant patients. Rejection is the most common post-transplant complication and the diagnosis of such is vital in order to guide immediate and appropriate treatment. In addition to the endomyocardial biopsy, noninvasive genetic testing can aid in rejection diagnosis and distinguish between cell-mediated and antibody-mediated rejection. We describe a case of glyphosate exposure in a post orthotopic heart transplant and the subsequent heart transplant rejection, patient’s clinical course, treatment, and follow up.

Use of Hepatitis C Viremic Donors to Expand the Pediatric Donor Pool.

The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors.