Admissions for posttransplant lymphoproliferative disorder: a 9-year longitudinal analysis of the National (Nationwide) Inpatient Sample.

Background: Posttransplant lymphoproliferative disorder (PTLD), a term that encompasses a wide array of malignancies that occur after transplant, can be one of the most devastating transplant complications. While there have been major advancements in care, especially after the landmark PTLD-1 trial in 2012, there is a paucity of information on hospitalizations for PTLD and the changes in hospitalizations over time. Methods: This retrospective cohort study used the National Inpatient Sample to identify hospitalizations for PTLD that occurred between 2009 and 2018. We extracted data for hospitalizations with a primary or secondary diagnosis of PTLD and examined a range of variables, including age, gender, race, hospital type, hospital location, and disposition status. We also collected data on hospital region, median household income, insurance status, and bed size. Results: There was a statistically significant increase in the number of hospitalizations from 2009 to 2019 and an increasing rate of hospitalizations over the study period. Hypertension, electrolyte imbalances, renal failure, and anemia were among the most common comorbidities. We found an increased mortality rate, but this was not statistically significant. Conclusion: Our study provides insight into the changes in hospitalizations for PTLD over nearly a decade, showing an increase in hospitalizations and reports of comorbidities.

The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD).

BACKGROUND: The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example. RESULTS: Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel. CONCLUSIONS: The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.

Posttransplant Lymphoproliferative Disorder in a Patient With Alpha-1 Antitrypsin Deficiency: A Case Report.

A 13-year-old male with a past medical history of receiving a whole liver transplant secondary to alpha-1 antitrypsin deficiency (AATD) with subsequent inferior vena cava thrombosis nine years prior presented to the emergency department with abdominal distension, shortness of breath, coughing, and left superficial cervical lymphadenopathy. He had seen his pediatrician the day before where he tested negative for group A Streptococcus, influenza, and severe acute respiratory syndrome coronavirus 2. Additionally, the patient reported having elevated liver function tests noted from the results of lab tests taken earlier that day. The patient was admitted to the hospital. While at the hospital, a lymph node biopsy was performed, and pathology from that biopsy revealed infectious mononucleosis-like nondestructive posttransplant lymphoproliferative disorder (PTLD). Due to the patient's liver transplant nine years prior, the patient was on an immunosuppressant medication: tacrolimus 2 mg. To treat the PTLD, the tacrolimus was reduced, then stopped, and then subsequently restarted at 1 mg. He also was given ganciclovir and prednisone. Two months after recovering from the PTLD, the patient's Epstein-Barr-virus (EBV) viral load continued to fluctuate, and he was treated with three doses of the monoclonal antibody drug rituximab. After treatment with rituximab, his EBV viral load remained stable. This case report gives insight into the treatment of PTLD and can serve as a reminder to be aware of the possibility of PTLD in a pediatric patient with AATD multiple years after a transplant.

Primary cutaneous EBV+ extranodal NK/T-cell lymphoma of gamma/delta T-cell lineage in the posttransplantation setting.

Posttransplantation primary cutaneous T-cell lymphomas (PT-CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT-CTCLs are typically EBV- and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75-year-old individual who developed skin lesions 30 years after liver transplantation. Pathologic evaluation of the skin biopsy revealed involvement by a clonal, EBV+ T-cell population of gamma/delta lineage with no evidence of systemic disease. Comprehensive genomic profiling was performed, confirming focal one-copy loss of 6q23.3, altogether consistent with the extremely rare and unusual diagnosis of primary cutaneous EBV+ extranodal NK/T-cell lymphoma of gamma/delta T-cell lineage in the posttransplantation setting.

Impact of prophylaxis with rituximab on EBV-related complications after allogeneic hematopoietic cell transplantation in children.

Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.

Investigation of atypical serological profiles for Epstein-Barr virus (EBV).

BACKGROUND: Commercial immunoassays that detect IgG and IgM directed toward VCA and IgG EBNA are used in combination to assess EBV immune status. However, this strategy does not always confirm/exclude recent/past EBV infection or absence of immunity. OBJECTIVES: The aim of our study was to perform complementary investigations on samples with atypical EBV serological profiles, in order to identify the clinical situation they correspond to. STUDY DESIGN: EBV serology was performed using EBV VCA IgM/IgG and EBNA IgG LXL® DiaSorin assay. Complementary investigations included ELISA IgM VCA, immunoblots, CMV IgM/IgG and CMV IgG avidity, and EBV PCR. RESULTS: In our study, 12810 EBV serological results were analyzed, and 3580 atypical profiles were detected (28 %). Among these latter, isolated VCA IgG represented 42.9 %, the three positive markers accounted for 29.1 %, isolated EBNA IgG represented 18.5 %, isolated VCA IgM accounted for 6.4 % and positive VCA IgM & positive EBNA IgG represented 3.1 %. VCA IgG detected alone were specific in 100 % cases and EBNA IgG detected alone were specific in 91.7 % cases. VCA IgM detected alone were false positive or due to a cross reaction with CMV in 52.8 % cases. The pattern positive VCA IgM and positive EBNA IgG correspond to a false positive in VCA IgM, EBNA IgG or both in 83.4 % cases. Positive EBV VCA IgM/IgG and EBNA IgG were unreliable to detect active EBV infection in 66.7 % cases. DISCUSSION: Atypical EBV serological profiles may correspond to several clinical situations and complementary investigations allow to determine the immune status in more than 98.5 % cases.

T-Cell Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Systemic Review.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Comparative analysis of tabelecleucel and current treatment in patients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease following hematopoietic cell transplant or solid organ transplant.

AIMS: With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. METHODS: In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. RESULTS: 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25-0.88) and adjusted HR of 0.37 (95% CI 0.20-0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. CONCLUSIONS: In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience.

BACKGROUND: Monomorphic post-transplant lymphoproliferative disorder (mPTLD) is a major cause of morbidity/mortality following solid organ transplant (SOT), with infection, mPTLD progression and organ rejection presenting equal risks. Balancing these risks is challenging, and the intensity of therapy required by individual patients is not defined. Although an increasing body of evidence supports the use of a stepwise escalation of therapy through reduction in immunosuppression (RIS) to rituximab monotherapy and low-dose chemo-immunotherapy, many centres still use B-cell non-Hodgkin lymphoma (B-NHL) protocols, especially when managing Burkitt/Burkitt-like (BL) PTLD. This study sought to define outcomes for children managed in the UK or Spanish centres using low-intensity first-line treatments. PROCEDURE: Retrospective data were anonymously collected on patients younger than 18 years of age, with post-SOT mPTLD diagnosed between 2000 and 2020. Only patients given low-intensity treatment at initial diagnosis were included. RESULTS: Fifty-six patients were identified. Age range was 0.9-18 years (median 10.7). Most (62.5%) had early-onset PTLD. Haematopathological analysis showed 75% were diffuse large B-cell like, 14.3% were BL and nine of 33 (27%) harboured a MYC-rearrangement. Stage III-IV disease was present in 78.6%. All but one had RIS, 26 received rituximab monotherapy and 24 low-dose chemo-immunotherapy, mostly R-COP. Intensified B-NHL chemotherapy was required in 10/56 (17.9%). There were a total of 13 deaths in this cohort, three related to PTLD progression. The 1-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 92.8%, 78.6% and 80.2%, respectively. CONCLUSIONS: R-COP provides an effective low-dose chemotherapy option. Escalation to more intensive therapies in the minority of inadequately controlled patients is an effective strategy.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant.

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.

A Case of Epstein-Barr Virus-Negative Post-transplant Lymphoproliferative Disorder in a Solid Organ Transplant Recipient With Untreated Chronic Hepatitis C.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies affecting solid organ transplant recipients. The disease is frequently associated with Epstein-Barr virus (EBV) infection (70% of cases) and cases are often delineated by EBV positivity status. The oncogenesis of EBV-positive PTLD is well-described in the literature; however, the etiology of the EBV-negative subtype is poorly understood. This report describes a case of EBV-negative PTLD developing in a combined kidney-pancreas transplant recipient with an incidental finding of untreated chronic hepatitis C virus (HCV). Our experience suggests an association between HCV and EBV-negative PTLD. Additional well-designed studies are needed to further investigate this association.

Global research productivity of post-transplant lymphoproliferative disorder: a bibliometric study.

Background: Post-transplant lymphoproliferative diseases (PTLD) are a heterogeneous collection of neoplasms that occur after solid organ transplants (SOT). In the past 20 years, there has been a rise in PTLD research. This study aims to investigate the global research output and interest regarding PTLD using a bibliometric approach. Material and methods: On 28 November 2022, the Web of Science Core Collection documents on PTLD published between 2000 and 2022 were collected and analyzed using bibliometric techniques. The VOSviewer application was utilized to visualize the annual number of publications, authors, organizations, countries, published journals, citations, and most occurring keywords. Results: A total of 2814 documents were retrieved, and a screening process included 1809 documents. The total number of citations was 45 239, and the average number per item was 25. Most articles (n = 747) and citations (n = 25 740) were produced in the United States. Based on citations, most of the top 10 institutions that contributed were in the United States of America. The University of Pittsburgh topped the list with 2700 citations and 64 articles. The vast majority of articles were published in Pediatric Transplantation (n = 147), Transplantation (n = 124), and the American Journal of Transplantation (n = 98). Transplantation has received the most citations, 6499, followed by the American Journal of Transplantation with 5958 citations and Blood with 4107 citations. Conclusion: With ongoing debates over optimal classification, Epstein-Bar virus involvement, and treatment, this topic has received significant interest from researchers in recent years. Our results can be used as a guide for future research in the field and as a framework for a more in-depth look at the scientific progress of PTLD.

Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch.

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.

Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?

Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.

Epstein Barr virus-directed T-cell therapy for refractory EBV-PTLD in a toddler post Orthotopic heart transplantation.

Epstein-Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post-transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV-directed T cells in rituximab-refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV-PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV-directed T-cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV-directed T-cell therapy for management and associated pitfalls.