Post-transplant Lymphoproliferative Disorder Research Articles

A case of a systemic cancer-associated thrombosis successfully treated with multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy

Abstract Background Cancer-associated thrombosis (CAT) is one of the major complications during the treatment course of cancer, which often challenges clinicians in daily clinical practice despite anticoagulation therapy. Case summary A 57-year-old man with a history of a liver transplantation was diagnosed with post-transplant lymphoproliferative disorders. He developed severe systemic thromboses including a massive pulmonary embolism and was treated with anticoagulation therapy including a factor Xa inhibitor. However, the systemic thromboses worsened despite the anticoagulation therapy. During the acute treatment course of the thromboses, we administered anticancer drug therapy in hopes of an improvement in the activity of the cancer status leading to a favourable effect on the thrombosis status. Multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy successfully improved the systemic thrombosis. Discussion Anticoagulation therapy is a standard treatment for CAT; however, some cases of CAT do not successfully improve despite anticoagulation therapy, partly due to a highly active cancer status. Anticancer drug therapy might increase the risk of a thrombosis, whereas it could improve the activity of the cancer status leading to a decreased risk of a thrombosis. A multi-disciplinary therapy might be a reasonable option especially for CAT with a highly active cancer status.

FDG PET/CT Findings of Renal Cell Carcinoma Arising From a Transplanted Kidney in a Pediatric Patient.

A 12-year-old girl presented with a history of kidney transplant complicated by posttransplant lymphoproliferative disease. A solid mass was found in the lower pole of the transplanted kidney, concerning for posttransplant lymphoproliferative disease. However, biopsy confirmed papillary renal cell carcinoma. FDG PET/CT showed increased activity in the known renal cell carcinoma in the renal allograft.

Case report on prolonged kidney graft survival without immunosuppressive therapy after allogeneic hematopoietic stem cell transplantation

Background. The possibility of inducing immunological tolerance in allogeneic organ transplant recipients is a research goal of the transplantology community, as it will ensure the likelihood of complete engraftment of a foreign organ. However, such a task presently remains difficult to accomplish.Objective: to demonstrate longterm kidney graft survival without signs of acute rejection and without immunosuppressive therapy in a patient who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a haploidentical donor for post-transplant lymphoproliferative disorder (PTLD).Methods and materials. Recipient’s graft function was assessed using clinical, laboratory, instrumental and pathomorphological examination methods. Results. With no immunosuppressive therapy for more than four years, the kidney recipient showed stable, satisfactory graft function.Conclusion. The described clinical case demonstrates the development of immunological tolerance to a kidney graft in a recipient of allogeneic hematopoietic stem cells (HSCs).

Medium-term Outcomes in Pediatric Heart Transplant Recipients Managed Using a Steroid Avoidance Immune Suppression Protocol.

Short-term outcomes using steroid avoidance immune suppression are encouraging in pediatric heart transplant (HT) recipients at low risk of antibody-mediated rejection. We assessed medium-term outcomes in pediatric HT recipients initiated on a steroid avoidance protocol at our institution using surveillance biopsies. All primary HT recipients during 2006-2020 who did not have a donor-specific antibody were eligible for immune suppression consisting of 5-d Thymoglobulin/steroid induction followed by a tacrolimus-based, steroid-free regimen. We assessed freedom from graft failure (death or retransplant), acute rejection, posttransplant lymphoproliferative disease, and cardiac allograft vasculopathy. Overall, 150 of 181 primary HT recipients were eligible for steroid avoidance regimen. Their median age was 8.7 y, 41% had congenital heart disease, 23% were sensitized, and 35% were on a mechanical support. The median follow-up was 6.1 y. Eleven patients (8%) were on maintenance steroids at discharge and 13% at 1 y. Graft survival was 94% at 1 y and 87% at 5 y. Freedom from rejection was 73% at 1 y and 64% at 5 y. Freedom from posttransplant lymphoproliferative disease was 96% at 1 y and 95% at 5 y. Freedom from moderate cardiac allograft vasculopathy was 94% at 5 y. Eight patients developed diabetes. Estimated glomerular filtration rate was <60 mL/min/1.73 m2 in 5% of the cohort at 5 y. Pediatric HT recipients at low risk of antibody-mediated rejection have excellent medium-term survival and relatively low incidence of posttransplant morbidities when managed using a steroid avoidance immune suppression protocol.

Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children

IntroductionPaediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood....

S3805 EBV-Negative Post-Transplant Lymphoproliferative Disorder Presenting as Multiple LI- RADS M Lesions on MRI

S3805 EBV-Negative Post-Transplant Lymphoproliferative Disorder Presenting as Multiple LI- RADS M Lesions on MRI

S3477 Uncommon Presentation of Post-Transplant Lymphoproliferative Disorder in a Liver Transplant Recipient

S3477 Uncommon Presentation of Post-Transplant Lymphoproliferative Disorder in a Liver Transplant Recipient

Programmed cell death ligand 1 expression associated with subtypes of post-transplant lymphoproliferative disorder among pediatric kidney transplant recipients.

Programmed cell death ligand 1 (PD-L1) expression on tumor cells engages the PD-1 receptor on T cells, inhibiting anti-tumor responses. PD-L1 has been detected in cases of post-transplant lymphoproliferative disorder (PTLD) but reports are limited. Here we examine PD-L1 expression and evaluate for clinical correlations. Twenty-one cases of PTLD were identified among pediatric kidney transplant recipients at our institution from February 1996 to April 2017. Using paraffin-embedded tissue biopsies, we examined 21 primary tumors for expression using PD-L1 monoclonal antibody performed with PAX5 as a double stain. We scored expression of PD-L1 on lesional B-cells as a percentage of positive cells. Clinical course and outcome were obtained from retrospective chart review. Applying revised 2017 WHO PTLD classification showed five non-destructive, nine polymorphic, and seven monomorphic cases. Average PD-L1 expression based upon PTLD subtype was: non-destructive 11%, polymorphic 43%, and monomorphic 73% (p=.01). Two patients transferred shortly after diagnosis, five received chemotherapy, and three died from PTLD. Among the fatalities, all showed monomorphic PTLD and 90% of lesional B-cells expressed PD-L1. In this case series, significant differences in PD-L1 expression were seen among different subtypes, and monomorphic PTLD demonstrated the highest expression. Study of a larger cohort is needed, and if the correlation of PD-L1 expression and PTLD subtype is confirmed, this may highlight the potential utility of checkpoint inhibitor therapy in cases of severe or refractory disease among kidney transplant recipient in whom the risk of allograft loss is acceptable given the option of chronic dialysis.

The pathobiology of select adolescent young adult lymphomas.

Lymphoid cancers are among the most frequent cancers diagnosed in adolescents and young adults (AYA), ranging from approximately 30%-35% of cancer diagnoses in adolescent patients (age 10-19) to approximately 10% in patients aged 30-39 years. Moreover, the specific distribution of lymphoid cancer types varies by age with substantial shifts in the subtype distributions between pediatric, AYA, adult, and older adult patients. Currently, biology studies specific to AYA lymphomas are rare and therefore insight into age-related pathogenesis is incomplete. This review focuses on the paradigmatic epidemiology and pathogenesis of select lymphomas, occurring in the AYA patient population. With the example of posttransplant lymphoproliferative disorders, nodular lymphocyte-predominant Hodgkin lymphoma, follicular lymphoma (incl. pediatric-type follicular lymphoma), and mediastinal lymphomas (incl. classic Hodgkin lymphoma, primary mediastinal large B cell lymphoma and mediastinal gray zone lymphoma), we here illustrate the current state-of-the-art in lymphoma classification, recent molecular insights including genomics, and translational opportunities. To improve outcome and quality of life, international collaboration in consortia dedicated to AYA lymphoma is needed to overcome challenges related to siloed biospecimens and data collections as well as to develop studies designed specifically for this unique population.

Diagnostic Challenge in Renal Transplantation: Splenosis vs. Post-Transplant Lymphoproliferative Disorder—A Case Report

Splenosis is a benign, acquired condition characterized by the auto-implantation of focal deposits of splenic tissue throughout the peritoneal cavity, most commonly occurring after splenic injury and/or splenectomy. Post-Transplant Lymphoproliferative Disorder (PTLD) is a well-known complication of solid organ transplantation that results from unregulated B-cell proliferation due to chronic immunosuppression. Given their clinical and radiologic similarities, these two entities may pose a diagnostic dilemma in select solid-organ transplant recipients. We present the case of a 54-year-old kidney-transplant recipient presenting with abdominal pain and found to have a retroperitoneal soft-tissue mass concerning for PTLD. He underwent a CT-guided biopsy of the mass, and histopathological studies revealed lymphoid tissue consistent with splenic tissue, thus ruling out PTLD. The patient subsequently underwent symptomatic management, with the eventual resolution of his symptoms. The early diagnosis of PTLD is paramount, as prompt intervention has a substantial impact on the high rate of morbidity and mortality associated with this condition. Additionally, the diagnosis of splenosis in the setting of a retroperitoneal mass is critical in order to avoid invasive diagnostic and therapeutic procedures that may result in significant complications. A detailed surgical history, including prior splenic trauma and/or splenectomy, should raise clinical suspicion for splenosis and guide further diagnostic and therapeutic decision making.

A pediatric case series of catastrophic gastrointestinal complications of posttransplant lymphoproliferative disease with increasing incidence, high association with coronavirus disease 2019, higher mortality, and a plea for early endoscopy to prevent late fatal outcome

BackgroundPosttransplant lymphoproliferative disorder is one of the most severe complications after transplantation, caused by uncontrolled proliferation of Epstein–Barr virus-positive B-cells in the setting of chronic immunosuppression. As one of the biggest transplant centers worldwide, we observed a potential increase in the number of patients with posttransplant lymphoproliferative disorder presenting with gastrointestinal symptoms in 1 year, during the coronavirus disease 2019 pandemic. There is limited information about dysregulation of the immune system following coronavirus disease 2019 infection, which may lead to Epstein–Barr virus reactivation in Epstein–Barr virus-positive B-cells and development of posttransplant lymphoproliferative disorder. Furthermore, there is no consensus in literature on a modality that can help in early diagnosis of posttransplant lymphoproliferative disorder with nonspecific gastrointestinal presentations before late and fatal complications occur.Case presentationOur case series includes five Iranian (Persian) patients, three female (2, 2.5, and 5 years old) and two male (2 and 2.5 years old), who developed gastrointestinal posttransplant lymphoproliferative disorder after liver transplantation. All of our patients were on a similar immunosuppressant regimen and had similar Epstein–Barr virus serologic status (seronegative at time of transplantation but seropositive at time of posttransplant lymphoproliferative disorder diagnosis). Four patients had either a positive coronavirus disease 2019 polymerase chain reaction test or exposure within the family. Although all of our patients presented with nonspecific gastrointestinal symptoms, four patients developed late posttransplant lymphoproliferative disorder complications such as bowel perforation and obstruction. All five patients with gastrointestinal posttransplant lymphoproliferative disorder received chemotherapy, but only two survived and currently are continuing the therapy. In one of the surviving patients, prompt endoscopic investigation resulted in early diagnosis of posttransplant lymphoproliferative disorder and a better outcome.ConclusionSince 80% of our patients had exposure to coronavirus, a potential relationship might be suggested between the two. Furthermore, as we witnessed in one case, urgent endoscopic investigation in immunocompromised patients presenting with gastrointestinal symptoms can improve the clinical outcomes and therefore should be considered for early diagnosis of posttransplant lymphoproliferative disorder.

More than four decades of graft survival in pediatric kidney transplant recipients.

Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40years of graft survival currently alive with a functioning first graft. We reviewed all pediatric (age < 18years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions. We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0years (IQR: 43.1, 48.1)). The median age at transplant was 13.8years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30years, 67.7 (IQR: 63.2, 91.8); and at 40years, 80.3ml/min/1.73 m2 (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease). Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.

Immunosuppression-Free Life after Pediatric Liver Transplant: A Case-Control Study from the Society of Pediatric Liver Transplant (SPLIT) Registry

To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. This was a retrospective case-control study. SPLIT participants <18years of age, ≥4years after isolated LT, and off IS for ≥1year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.

PD-L1 and PD-1 expression in pediatric post-transplant Burkitt lymphoma and other monomorphic post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorders (PTLD) develop as a consequence of immune suppression. Programmed death protein 1 (PD-1), a regulator of host immune activation, binds to programmed death-ligand 1 (PD-L1) to suppress the T-cell immune response. PD-1/PD-L1 pathway may play a role in PTLD. The objective was to describe intratumoral expression of PD-L1 and PD-1 in pediatric monomorphic PTLD, and assess if density of these cells is associated with progression-free survival (PFS) and overall survival (OS). Clinical variables and outcome data were collected on B-cell monomorphic PTLD treated in Toronto, Canada between 2000 and 2017. Diagnostic area from tumor tissue was identified to count CD3-positive or PD-1-positive cells and CD3-negative lymphoma B cells or PD-L1-positive cells. CD3+ , PD-1+ , and PD-L1+ cell densities were compared between cases of PTLD. OS and PFS were analyzed. We identified 25 cases of B-cell monomorphic PTLD; majority Burkitt lymphoma (32%) and diffuse large B-cell lymphoma (56%). All cases had CD3+ cells infiltrating the tumor, and median percentage of CD3+ cells was 14% (interquartile range: 6.2%-25%). Twelve cases (48%) had PD-1+ cell infiltrating (range: 1%-83%) and 13 cases (52%) had no PD-1+ cells infiltrating. Sixteen cases (64%) had PD-L1+ cells present; however, there was no PD-L1 expression on any Burkitt lymphoma tissue. When comparing PD-1 and PD-L1 expression, there was no difference in OS or PFS. Intratumoral presence of PD-1+ and PD-L1+ cells varied in pediatric patients with monomorphic PTLD; however, no relationship to OS and PFS was identified.

Primary sclerosing cholangitis and other risk factors for post-transplant lymphoproliferative disease after liver transplantation in adults.

Post-transplant lymphoproliferative disease (PTLD) is a rare but serious complication of liver transplantation (LT) with morbidity and mortality. The risk factors for PTLD in adults are ill-defined. This study aimed to assess the risk factors for PTLD after LT in adults. All adult LT recipients between 1986 and 2016 from 2 centers in the Netherlands were included, with follow-up until 2020. PTLD was diagnosed according to the World Health Organization (WHO) classification. Potential risk factors for PTLD were assessed using multivariate Cox regression analysis. A total of 1281 patients were included, of whom 29 (2.3%) developed PTLD. Results show that independent risk factors for PTLD after LT in adults were no Epstein-Barr virus load monitoring strategy, primary sclerosing cholangitis as an indication for LT, era (historic era linked to more intense long-term immunosuppression), and Epstein-Barr virus-seronegative recipient. No other independent risk factors were identified in this study. Of the 207 patients with primary sclerosing cholangitis as an indication for LT, 13 (6.3%) developed PTLD versus 16 out of 1074 (1.5%) patients with other underlying liver diseases (log-rank p <0.001). The yearly PTLD incidence was higher in the first year than in the later years after LT (2.4%/y vs. 0.6%/y) for primary sclerosing cholangitis, but not for other indications (0.16%/y). In Epstein-Barr virus-seronegative recipients PTLD occurred earlier after LT, while in 97% of seropositive recipients it could occur very late after LT.

Abstract 2 Results of an Open Label Expanded Access Study of Omidubicel-onlv for Allogeneic Transplantation (allo-HCT) in Patients with Hematologic Malignancies

Abstract Introduction Omidubicel, a nicotinamide expanded allogeneic hematopoietic progenitor cell therapy derived from umbilical cord blood (UCB) was recently FDA approved for use as a sole donor source in allo-HCT based on phase III study results showing improved hematopoietic recovery and decreased infection rate compared to standard UCB. Objectives Open label, single arm expanded access program (EAP) evaluating clinical outcomes for patients with hematologic malignancies following omidubicel allo-HCT. Methods Eligible patients (&amp;gt;12 years) received myeloablative conditioning with supportive care per institutional guidelines. Patients were followed for engraftment, infections, graft versus host disease (GVHD), and two year post-transplantation outcomes. Results Between July 2020 and April 2023, 36 patients were enrolled at 5 US centers, and 29 (18 male, 11 female) were transplanted; median age was 38 years (range: 20-73); 55.2% white, 17.2% Black, 20.7% Asian, 10.3% other. Diagnoses included AML (37.9%), ALL (27.6%), MDS (20.7%) and other (13.8%). Median transplanted CD34+ cell dose was 5.6x106 cells/kg and HLA match was 4/6 in 51.7%, 5/6 in 44.8%, and 6/6 in 3.5%. Median follow-up was 6.25 months (range 0.33-27.7). At 100 and 365 days post-transplant, PFS rates were 95.5% and 82.9%, and OS rates were 96.3% and 84.4%, respectively. No infusion reactions were reported. Median neutrophil (&amp;gt;500/µl x3 days) and platelets (&amp;gt;20,000/µl x7 days) engraftment times were 12 and 33 days, respectively. Primary graft failure occurred in 2 (6.9%) patients, both alive &amp;gt;100 days after second transplant. Incidence of first grade 2 or 3 bacterial, viral, or invasive fungal infections through 100 days post-transplantation were 13.8%, 24.1% and 0%, respectively. Acute GVHD was reported in 13 (44.8%) patients (grade II: 34.5%, grade III: 10.3%) and mild chronic GVHD in 1 (3.5%). There were 4 deaths (13.8%): 2 due to relapse @275 and 381 days, 1 due to infection (day 135) and 1 due to pulmonary failure on day 10. Post-transplant lymphoproliferative disease was reported in one. Discussio In this real-world EAP setting, allo-HCT with omidubicel was well tolerated, and observed engraftment and infections consistent with published Phase 3 data. These data further support the role of omidubicel particularly for patients from diverse racial backgrounds.

Long-term management and outcome of lung transplantation in Japan.

The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.

ABCL-484 First Use of Upfront Polatuzumab Vedotin in Post-Transplant Lymphoproliferative Disorder

ABCL-484 First Use of Upfront Polatuzumab Vedotin in Post-Transplant Lymphoproliferative Disorder

A case of post renal transplant PTLD of lung.

Post Transplant Lymphoproliferative Disorder (PTLD) is a heterogeneous group of Lymphoid proliferative disorders that occur in patients post Hematogenous or Solid organ transplants. They are closely associated with Ebstein-Barr Virus and can range from polyclonal lesions to frank lymphomas. PTLD is usually a rare post-transplant complication, with the incidence being higher post Lung or Heart Transplantation and less commonly seen post-renal transplantation. The incidence post renal transplantation is less than 1%, with most of the cases being limited to the Gastro-Intestinal Tract and Lymph nodes, and incidence in the lungs being extremely rare. Here we present a case report of PTLD of the lung in a post-renal transplant recipient.

Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy.

The in vitro growth transformation of primary B cells by Epstein-Barr virus (EBV) is the initial step in the development of posttransplant lymphoproliferative disorder (PTLD). We performed electron microscopic analysis and immunostaining of primary B cells infected with wild-type EBV. Interestingly, the nucleolar size was increased by two days after infection. A recent study found that nucleolar hypertrophy, which is caused by the induction of the IMPDH2 gene, is required for the efficient promotion of growth in cancers. In the present study, RNA-seq revealed that the IMPDH2 gene was significantly induced by EBV and that its level peaked at day 2. Even without EBV infection, the activation of primary B cells by the CD40 ligand and interleukin-4 increased IMPDH2 expression and nucleolar hypertrophy. Using EBNA2 or LMP1 knockout viruses, we found that EBNA2 and MYC, but not LMP1, induced the IMPDH2 gene during primary infections. IMPDH2 inhibition by mycophenolic acid (MPA) blocked the growth transformation of primary B cells by EBV, leading to smaller nucleoli, nuclei, and cells. Mycophenolate mofetil (MMF), which is a prodrug of MPA that is approved for use as an immunosuppressant, was tested in a mouse xenograft model. Oral MMF significantly improved the survival of mice and reduced splenomegaly. Taken together, these results indicate that EBV induces IMPDH2 expression through EBNA2-dependent and MYC-dependent mechanisms, leading to the hypertrophy of the nucleoli, nuclei, and cells as well as efficient cell proliferation. Our results provide basic evidence that IMPDH2 induction and nucleolar enlargement are crucial for B cell transformation by EBV. In addition, the use of MMF suppresses PTLD. IMPORTANCE EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).