Prevention Of Post-transplant Lymphoproliferative Disease Research Articles

Intravenous Immunoglobulin G (IVIg) and Ganciclovir or Valganciclovir for the Treatment of Ebstein Barr Virus (EBV) Viremia and Prevention of Post-Transplant Lymphoproliferative Disease (PTLD) in Pediatric Heart Transplant Recipients

<h3>Purpose</h3> EBV viremia can progress to a potentially fatal PTLD. Data on the use of IVIg and antiviral agents such as ganciclovir or valganciclovir for the treatment (Rx) of this condition are limited. This study retrospectively evaluated the efficacy of IVIg with the combination of antiviral therapy in reducing EBV viral load and preventing PTLD in pediatric heart transplant patients (pts). <h3>Methods</h3> All pts transplanted since December 2007 were included. IVIg plus antiviral was implemented as empiric Rx in clinically significant EBV viremia polymerase chain reaction (PCR) > 100,000 copies/mL). Pts who were refractory to this tx and had EBV PCR > 250,000 copies/mL received rituximab. The pts were divided into two groups, those that received empiric Rx and those that did not. Pts who did not receive empiric Rx never had EBV viremia or only had EBV viremia at the time of PTLD diagnosis. The change from baseline EBV PCR values over time was evaluated, and the actuarial freedom from PTLD was compared between the two groups. <h3>Results</h3> There were 88 pts in the non-Rx group and 18 pts in the empiric Rx group. In the empiric Rx group, 9 pts received rituximab. The median time of initial EBV viremia incident was 27.7 months after transplantation. Pts on empiric Rx experienced an initial decrease in EBV viral load (p = 0.009) and maintain an acceptable EBV PCR level compared to baseline. None of the treated pts, including those who were refractory, developed PTLD. In the non-Rx group, 5 pts developed PTLD (p = 0.272). <h3>Conclusion</h3> A clinically important finding was observed when EBV viremia was identified with steps implemented to minimize viral load by utilizing IVIg, antivirals, and rituximab. It appeared that PTLD may be avoided though our data did not yet reach statistical significance. A large prospective clinical trial is indicated to support the use of this empiric Rx for the prevention of PTLD.

A RARE CAUSE OF CRAZY PAVING: POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Crazy paving on computed tomography (CT) is defined as interlobular septal thickening with areas of ground glass attenuation. It can be caused by a variety of pathologies. Here we describe an unusual cause of crazy paving in an immunosuppressed patient. CASE PRESENTATION: A 58-year old man presented for syncope. His past medical history included acute myelogenous leukemia in complete remission post stem cell transplant, and complicated by cytomegalovirus colitis. Upon arrival to the emergency department, he was found to be obtunded and was intubated. Home medications included tacrolimus, ganciclovir, sulfamethoxazole-trimethoprim, and voriconazole. Vital signs were significant for a blood pressure of 62/38mmHg and heart rate of 138/minute. Laboratory studies revealed a white blood cell count of 13.6K/mm3, with 15% lymphocytes, 5% atypical lymphocytes, 34% plasmacytes, and 44% neutrophils. Lactic acid was 10.8mmol/L, bicarbonate 15mmol/L, and creatinine 3mg/dL. Arterial blood gas was consistent with metabolic acidosis. Tacrolimus level was 6ng/mL (goal 5-10). Computed tomography (CT) of the chest (Images 1-3) revealed interlobular septal thickening with ground glass opacities, and prominent mediastinal, cervical, and axillary lymphadenopathy. The patient required vasopressor support and was started on broad spectrum antibiotics, antivirals, antifungals. Bronchoalveolar lavage showed 38% neutrophils, 52% monocytes, and 10% lymphocytes. Gram stain, cultures, stain for acid fast bacilli, cytology, galactomannan, fungal cultures, and viral respiratory panel were negative. Serum flow cytometry revealed plasmacytoid cells with positive Epstein-Barr virus (EBV) in situ hybridization. Serum EBV PCR showed >39,000,000 copies/mL. These findings were consistent with post-transplant lymphoproliferative disease (PTLD). DISCUSSION: PTLD is a category of lymphoid disorders that arise after solid organ or hematopoietic transplants in the setting of active immunosuppression, most commonly with active EBV infection. Severity is graded as early, polymorphic, or monomorphic. Treatment can involve decreasing immunosuppression, rituximab in CD20+ disease, chemotherapy (with surgery if localized disease), or EBV-targeted cytotoxic T-cell instillation. Prevention of PTLD in transplant patients has included rapid tapering of immunosuppression as appropriate, and close monitoring of EBV viral levels, with elevations prompting reduction in immunosuppression or initiation of rituximab. Given its in vitro inhibition of EBV replication, ganciclovir has been suggested prophylactically, but there is no consensus regarding antiviral prophylaxis. CONCLUSIONS: Our patient rapidly decompensated and went into multiorgan system failure; he was made comfort care and expired. This case demonstrates the need for a high index of suspicion for PTLD in all transplanted patients with crazy paving present on imaging. Reference #1: Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease: risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013 September; 8(3): 173-183. Reference #2: Rossi SE, Erasmus JJ, Volpacchio M, et al. "Crazy Paving” pattern at thin-section CT of the lungs: radiologic-pathologic overview. Radiographics 2003; 26 (6): 1509-1519. Reference #3: AlDabbagh, MR, Gitman MR, Kumar D et al. The Role of Antiviral Prophylaxis for the prevention of Epstein-Barr virus-associated posttransplant lymphoproliferative disease in solic organ transplant recipients: a systematic review. Am J Transplant. 2017; 17: 770-781. DISCLOSURES: No relevant relationships by Payam Nabizadeh, source=Web Response No relevant relationships by Paul Simpson, source=Web Response

The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.

The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients.

Everolimus Associated with Activated Vitamin D for Post-Transplant Increase Epstein-Barr-Virus Load Treatment. Two Case Reports

Post-transplant lymphoproliferative disease (PTLD) is an uncommon but life-threatening complication of solid-organ and blood stem-cell transplants. It is caused by an uncontrolled expansion of B lymphocytes infected with Epstein-Barr virus (EBV). It responds poorly to therapy, including reduction of immunosuppression, interferon, antivirals or chemotherapy. Therefore the optimal strategy for management is currently focused on prevention. Some centers have already introduced chemoprophylaxis and/or preemptive strategies using EBV viral load as a surveillance. Some experimental studies suggest that mTOR inhibitors inhibits growth of human EBV-transformed B lymphocytes and vitamin D had an immune response to EBV. We report two cases of an increased of blood BKV viral load after renal transplantation that were successfully treated with everolimus in association with calcitriol. This report suggests that everolimus associated with calcitriol could be an effective and safe treatment for the prevention of PTLD in transplant recipients.

Epstein-Barr Virus???DNA Load Monitoring Late After Lung Transplantation: A Surrogate Marker of the Degree of Immunosuppression and a Safe Guide to Reduce Immunosuppression

Posttransplant lymphoproliferative disease (PTLD) is a serious complication after lung transplantation and its relation with Epstein-Barr virus (EBV) is well recognized. It has been postulated that preemptive reduction of immunosuppression guided by EBV-DNA load may lead to a significantly lower incidence of PTLD, because of the reconstitution of T-cell control. In this report, we describe the feasibility of this approach in terms of safety with regard to the risk of acute as well as chronic allograft rejection in 75 lung transplant recipients transplanted between 1990 and 2001 and followed for this study from June 1, 2001 until January 1, 2006. From all patients visiting our outpatient clinic, EBV-DNA load was measured at least twice a year during the study period. In patients with positive results, measurements were repeated every two to four weeks. EBV reactivation was defined as two consecutive EBV-DNA load measurements with a rising trend; with the last measurement exceeding 10.000 copies/mL under stable immunosuppression. In such case, immunosuppression was reduced. EBV reactivation was observed in 26/75 patients (35%). One (1.5%) of these patients developed PTLD during the study period. Acute rejection, acceleration of chronic allograft rejection, or worse survival were not observed after reduction of immunosuppression. Preemptive reduction of immunosuppression after lung transplantation guided by EBV-DNA load appears to be a safe approach for the prevention of PTLD in lung transplant recipients late after transplantation.

Posttransplant lymphoproliferative disease: pathogenesis, monitoring, and therapy.

The spectrum of transplant-related lymphoproliferative diseases is expanding to include a variety of neoplasias that typically occur late after transplant including Epstein-Barr virus (EBV)-negative B- and T-cell lymphomas, EBV-positive T-cell lymphoma, myeloma, plasmacytoma, and Hodgkin's disease. New approaches to diagnosis and monitoring based on quantitative polymerase chain reaction for EBV DNA are being explored. What exactly is being measured (the source and character of the viral DNA) remains to be determined, as does the compartment that should be assayed (whole blood, serum, plasma, or lymphocytes). These questions not withstanding, there is an emerging consensus that these technologies will facilitate rapid diagnosis and therapeutic monitoring in the future. A myriad of therapeutic interventions are or will become available. Rituximab, alone or in addition to other therapies, promises a profound change in the landscape with regard to the treatment and perhaps the prevention of posttransplant lymphoproliferative disease. New approaches to adoptive cellular immunotherapy, including use of EBV-specific products from unrelated donors, nonspecifically activated autologous products, and genetically engineered T cells, are all being explored.