Gastrointestinal Involvement of Posttransplant Lymphoproliferative Disorder in Lung Transplant Recipients: Report of a Case

PURPOSE Lymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immuno-suppression. The gastrointestinal manifestations of posttransplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized. METHODS Case presentation and 16 previously reported cases of posttransplant lymphoproliferative disorder with gastrointestinal involvement are reviewed. RESULTS Patient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1–109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10–85) days. CONCLUSIONS Posttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.     

Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication

Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.     

Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy. Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than adults. The clinical presentation of PTLD varies from isolated lymphadenopathy to systemic disease; common sites involved are gastrointestinal tract, lung or airway, and cervical lesions. Timely and accurate diagnosis based on histological examination of biopsy tissue is essential for early intervention. Immunostaining for EBV and evaluation for clonality are needed. For prophylaxis when EBV viral loads are increasing or for initial treatment of early lesions or polymorphic PTLD, a reduction in immunosuppressive treatment is a key component of therapy, but caution is needed for possible rebound allograft rejection. Chemotherapy is indicated for patients with poor response to reduced immunosuppression and for highly aggressive monomorphic PTLD. The use of rituximab in combination with chemotherapy is effective. For the time being, avoiding excessive immunosuppression is the most effective strategy for reducing the incidence of PTLD. Calcineurin inhibitor (CNI) minimization with proliferation signal inhibitors (PSIs) or conversion from a CNI to a PSI might be useful for preventing both development of PTLD and allograft rejection.     

Diagnostic dilemma in pancreatic lymphoma

Summary Non-Hodgkin's lymphoma predominantly involving the pancreas is a rare tumor of the gastrointestinal tract. Diagnosis can be difficult, since lymphoma may mimic carcinoma or pancreatitis. Lymphoproliferative diseases induced by immunosuppressive therapy frequently occur in the gastrointestinal tract of posttransplant patients. However, pancreatic involvement of posttransplant lymphoma is an exceptional condition. We present the case of a cyclosporin-treated renal transplant recipient with pancreatic lymphoma mimicking carcinomatous or inflammatory tumors. The diagnostic difficulties and treatment options of pancreatic lymphoma as well as lymphoproliferative disorders in immunosuppressed renal recipients are discussed in light of the current literature.     

A low incidence of posttransplant lymphoproliferative disorder in 109 lung transplant recipients

STUDY OBJECTIVES: The incidence of posttransplant lymphoproliferative disorder (PTLD) has been reported to range from 6.4 to 20% in lung transplant (LT) recipients. Postulated contributing factors include Epstein-Barr virus (EBV) infection and the use of immunosuppression, particularly muromonab-CD3 (OKT3)(Orthoclone OKT-3; Ortho Biotech; Raritan, NJ). We sought to examine these PTLD risk factors in 109 LT recipients at our institution who survived > 1 month. DESIGN: Retrospective review of EBV serology of all LT recipients at our institution. Our standard transplant protocol includes OKT3 for induction and refractory rejection, as well as lifelong acyclovir for herpes prophylaxis. We do not perform EBV donor-recipient matching. SETTING: A university-based LT center. RESULTS: We found that 5 of 109 patients were serologically negative for EBV prior to lung transplantation, and all of these patients converted following lung transplantation. The mean time to conversion was 151 days (range, 11 to 365 days). One fatal case of PTLD was documented in an EBV seroconverter (one of five patients) 12 weeks status posttransplantation for lymphangioleiomyomatosis. One nonfatal extrathoracic PTLD was documented in a seropositive patient (1 of 104 patients) 33 months posttransplantation. CONCLUSIONS: We conclude the following: (1) PTLD in LT recipients may have a lower incidence (2 of 109 patients; 1.8%) than previously reported, despite an aggressive immunosuppressive regimen; and (2) the incidence of PTLD is higher in patients with primary EBV infection (20% vs 1%).     

Activation and adoptive transfer of Epstein–Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease

The treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD. These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.     

Epstein-Barr viral load and disease prediction in a large cohort of allogeneic stem cell transplant recipients.

BACKGROUND: We wanted to determine the clinical significance and predictability of Epstein-Barr virus (EBV) infections among a large cohort of recipients of allogeneic, unselected stem cell transplants. METHODS: During 1988-1999, a total of 5479 consecutive serum samples obtained during 406 transplantations performed in Helsinki, Finland, were retrospectively analyzed by quantitative polymerase chain reaction for the presence of EBV DNA. RESULTS: Overall, EBV DNA was noted in at least 1 serum sample for 57 patients (14.0%), of whom 22 (5.4%) were found to have progressively increasing and ultimately high (>50,000 copies/mL) EBV DNA levels (median level, 179,000 copies/mL). In addition, 16 patients (4.0%) had low EBV DNA levels (median level, 3260 copies/mL) in isolated sera before death. Among the transplant recipients who survived, transient EBV DNAemia (median level, 3110 copies/mL), which apparently corresponded to asymptomatic EBV infection, was noted in 19 patients (4.7%). CONCLUSIONS: Low-level EBV DNA positivity in serum occurs relatively frequently after stem cell transplantation and may subside without specific treatment. However, high EBV DNA levels (i.e., >50,000 copies/mL) are strong predictors for the development of posttransplantation lymphoproliferative disease, are not spontaneously reversible, and should be treated immediately. If the EBV DNA level is >or=50,000 copies/mL, the patient can be classified as having life-threatening EBV infection.     

Dynamic EBV gene loads in renal, hepatic, and cardiothoracic transplant recipients as determined by real-time PCR light cycler

BACKGROUND: Epstein-Barr virus (EBV) is recognised as one of the causative agents for most cases of post-transplant lymphoproliferative disease (PTLD). Elevated levels of EBV DNA are known to be associated with the onset of PTLD, but little information is available regarding how EBV loads change with time in asymptomatic transplant recipients following transplantation. Our aims were to study the trend of EBV loads in renal (RTx), hepatic, and cardiothoracic transplant recipients and to compare their EBV loads with other healthy and patient controls. METHODS: A prospective study was performed using a real-time TaqMan polymerase chain reaction technique to measure EBV DNA loads from three types of organ transplant recipients and haemodialysis patients (HD). Their results were then compared with those from the healthy controls (HC); monospot test negative (MN-) and infectious mononucleosis positive (IM+) patients; patients who were previously treated for PTLD (pPTLD); those who were currently diagnosed to have PTLD (PTLD+); and patients who had a stable renal, hepatic, or cardiothoracic graft for more than a year. RESULTS: Post-transplant EBV loads were significantly higher than the pre-transplant levels. Asymptomatic transplant recipients were differentiated from the PTLD+group at 600 genome copies of EBV/mug DNA, and from IM+group at 100 genome copies. Both HC and MN- groups had significantly lower EBV loads than the three transplant groups. The dynamic change of EBV loads in RTx was greater in the first post-transplant month when compared with the HD group. All transplant recipients had transient rises of EBV loads whereas EBV load continued to rise in one suspected PTLD patient. CONCLUSIONS: Asymptomatic transplant recipients had higher baseline post-transplant EBV levels than the non-transplant and MN- groups. The rising post-transplant EBV load in these transplant recipients did not seem to be sustained for longer than 2 weeks. However, in a PTLD+patient the rising EBV load continued over a period of 4 weeks. Hence, the dynamic pattern of EBV loads is more important than absolute EBV DNA measurements alone in identifying those who might go on to develop PTLD.     

Epstein-Barr-Virus-Infektion nach pädiatrischer Nierentransplantation

Due to its mild cytopathic effects, Epstein-Barr virus (EBV) rarely causes severe clinical symptoms in immunocompetent hosts. While infants often remain asymptomatic during EBV infections, young immunocompetent adolescents and adults typically develop signs of infectious mononucleosis. Also, immunocompromised pediatric renal transplant recipients exhibit mostly mild acute EBV-related clinical symptoms. However, immunosuppressive therapy after pediatric renal transplantation may lead to an uncontrolled malignant proliferation of EBV infected B cells, due to the lack of T cell-specific regulation, and thus to post-transplant lymphoproliferative disease (PTLD). Pediatric patients bear an increased risk of PTLD, as they are often EBV seronegative at the time of transplantation and develop EBV primary infection after receiving an EBV positive kidney. The EBV-specific serology and EBV viral load constitute insufficient surrogate markers for the risk assessment of PTLD. An uncritical reduction of immunosuppressive therapy, based solely on the presence of a high, persistent EBV load, may put patients at risk of transplant rejection and subsequent graft failure and should therefore be avoided. Treatment of PTLD comprises reduction of immunosuppression, administration of rituximab in cases of CD20 antigen expression and possibly chemotherapy. The 5-year survival rate after PTLD amounts to approximately 61–87%, with involvement of the bone marrow and/or central nervous system being a risk factor for poor survival. An EBV vaccine is currently not available. An antiviral chemoprophylaxis with (val-)ganciclovir, however, reduces the incidence of EBV primary infection in patients with a high-risk seroconstellation (donor EBV positive, recipient EBV negative) and, hence, potentially the rate of PTLD.     

Diffuse lymphoproliferative disease after renal transplantation and its relation with Epstein-Barr virus. Experience at one center

Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients which appear to be related to Epstein Barr Virus (EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and CMV disease have been identified as risk factors that may tigger development of PTLD. We have studied the incidence of PTLD and its relationship with EBV in 588 adult renal transplant recipients who were transplanted in our hospital from 1988 to 2001. We have also evaluated the diagnostic and therapeutic methods used, the risk factors and outcome of the patients who developed PTLD. We identified 8 recipients (4 males and 4 females), range from 18 to 67 years (mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years (0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had CMV disease, two of them (25%) had been treated with hight doses of prednisolone, another was EBV seronegative, but the rest of them (50%) had no risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was based on the histology of biopsy and the last one by CT scans of chest-abdomen and cytology. The presence of EBV in the lymphoproliferative cells was assessed in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was poor. Five out of 8 patients died shortly after diagnosis as a direct consecuence of PTLD and another of an infectious complication of the treatment (75%). The 2 patients alive started dialysis and 1 of them died 2 years later of a non-related cause. In conclusion, PTLD is a relatively frequent disease with a poor prognosis in renal transplant patients. It seems to have a close relationship with EBV and can develop in the absence of the classical risk factors.     

Post‐transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review

Post‐transplant lymphoproliferative disorder (PTLD) is one of the life‐threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein–Barr virus (EBV). We herein report 2 cases of EBV‐associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced‐stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV‐associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.     

The biology of Epstein–Barr virus in post-transplant lymphoproliferative disease

Post-transplant lymphoproliferative disease (PTLD) is a B cell proliferative disorder that is associated with Epstein–Barr virus (EBV), an ubiquitous herpesvirus. EBV-seronegative organ transplant recipients are at highest risk. EBV infection in PTLD lesions exists in a latent rather than lytic state, making tumor regression in response to antiviral agents unlikely. Viral latency proteins drive proliferation of T cells but also allow T cells to target PTLD lesions for destruction. Augmentation of the cellular immune response via the infusion of EBV-specific cytotoxic T cells has yielded promising results in the prevention and treatment of PTLD in bone marrow transplant recipients. Efforts to extend this strategy to solid organ transplant recipients are ongoing. Editor’s comment: The spectrum of post-transplant lymphoproliferative disease includes both B- and T-cell malignancies. While the vast majority are EBV-associated, there is a growing subset without obvious EBV markers. Given the present state of the art, which is summarized in this paper, we are incapable of stratifying patients in terms of prognosis or the likelihood of clinical response to reduction in immune suppression or to chemotherapy. The goal for multicenter trials must include the development of uniform definitions for the clinical and virologic manifestations of PTLD, as well as further attempts to define the natural history of this group of diseases. Jay A. Fishman, M.D.     

Subacute immune response to primary EBV infection leading to post‐transplant lymphoproliferative disease in a renal transplant patient

A 23‐year‐old man sero‐negative for Epstein–Barr virus (EBV) developed recurrent sore throats 3 and 6 months after a renal transplant from an EBV sero‐positive donor. Tonsillar biopsy at 9 months post‐transplant showed post‐transplant lymphoproliferative disease (PTLD) caused by EBV. Following reduction of immunosuppressive treatment, he developed further signs and symptoms, and serological evidence of infectious mononucleosis followed by resolution of lymphadenopathy. This case emphasizes the difficulty in interpreting EBV serology in immunosuppressed patients and the importance of pre‐transplant EBV serology.     

Control of Epstein-Barr virus load and lymphoproliferative disease by maintenance of CD8+ T lymphocytes in the T lymphocyte-depleted graft after bone marrow transplantation

Of 100 bone marrow transplant recipients, 30 (30%) received a CD4(+) lymphocyte-depleted graft (1x10(6) CD8(+) T lymphocytes/kg of body weight). Replication of Epstein-Barr virus (EBV) was observed in 40 patients (40%). The use of a CD4(+) lymphocyte-depleted graft was the only independent risk factor for replication of EBV (relative risk, 11.5; 95% confidence interval, 5.8-22.8; P<.0001). Nevertheless, EBV load in those patients was not higher than in the rest of patients, and the low EBV load prevented the development of lymphoproliferative disease. These results suggest that the presence of CD8(+) T lymphocytes in the bone marrow graft can control EBV load, thereby reducing the risk of developing lymphoproliferative disease.     

Identifying the patient at risk for post-transplant lymphoproliferative disorder

Abstract: Post-transplant lymphoproliferative disorders (PTLD) are a recognized complication of the immunosuppression required to prevent allograft rejection, occurring in 1–20% of recipients of solid organ transplants. Several factors greatly increase the risk of developing PTLD early post-transplant in any individual recipient. Epstein–Barr virus (EBV) infection is critical in the pathogenesis of the majority of these cases. Pre-transplant EBV seronegativity increases the incidence of PTLD 10- to 75-fold over that of EBV-seropositive recipients. Other risk factors include very young recipient age, cytomegalovirus infection or mismatching (donor positive–recipient negative), aggressive immunosuppression with conventional biologic agents, and the type of organ transplanted. In contrast, the risk of developing PTLD late in the post-transplant course does not appear to be influenced by the type of immunosuppressive agents employed, but rather by the duration of any immunosuppression. The role of EBV in late PTLD is also less certain, as a greater proportion of lesions are not associated with evidence of EBV infection. As the understanding of these risk factors has expanded, opportunities exist to target those populations at highest risk for the development of PTLD for aggressive monitoring and pre-emptive or prophylactic therapy. It is hoped that implementation of such strategies will render early PTLD a preventable complication of transplantation.     

Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus

Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are seen in immunocompromised hosts and in many lymphoid neoplasms associated with immunocompromise. The posttransplantation lymphoproliferative disorders (PT-LPDs) are a heterogeneous group of B-cell neoplasms that arise in the setting of immunosuppressive therapy, and are associated with EBV infection. Whether type A and/or type B EBV are associated with PT-LPDs is unknown. Therefore, we investigated 27 PT-LPD lesions from 22 solid- organ transplant recipients by polymerase chain reaction (PCR) at the EBNA-2 and EBNA-3c loci to detect sequence deletions that distinguish the two EBV families. Another locus, EBER, was examined by single- strand conformation polymorphism analysis (SSCP), in conjunction with direct sequencing in selected cases. Type A EBV was found in 24 of 27 cases (89%) as seen by amplification of the EBNA-2 and EBNA-3c regions. Four different EBER polymorphisms were detected, confirming the presence of different type A EBV isolates among these cases. Three cases were negative for infection by EBV. Surprisingly, despite the immunocompromised state of the hosts, none of the 27 PT-LPD lesions harbored type B EBV. Thus, although type B EBV may commonly infect peripheral blood lymphocytes in immunocompromised individuals, they do not appear to induce readily PT-LPD formation.     

Thoracic presentations of posttransplant lymphoproliferative disorders

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) are rare complications following transplantation. Although organ-specific cases have been reported, primary presentation in the thoracic cavity has not been fully characterized. METHODS: Eleven cases of PTLD with a primary thoracic presentation were identified among 3,085 solid-organ transplant patients and 1,662 bone marrow transplant patients from 1990 to 2001. RESULTS: There were eight men and three women with a mean age of 49 years. Transplanted organs included lungs (three patients), kidneys (three patients), kidney/pancreas (two patients), allogeneic bone marrow (two patients), and heart (one patient). The time to presentation ranged from 1 to 97 months (median time, 8 months). Six patients developed PTLD within 1 year of undergoing transplantation. Pretransplant serology for Epstein-Barr virus (EBV) and cytomegalovirus was negative in 80% and 78% of cases, respectively. Radiographic evaluation revealed mediastinal adenopathy in 45% of patients, and pulmonary parenchymal lesions in 55%. Fifty-five percent of patients also had extrathoracic involvement. Diagnosis was achieved by CT-guided transthoracic needle biopsy in eight patients, and by open biopsy in three patients. Pathologic analysis revealed monomorphic PTLD (ie, diffuse large B-cell lymphoma) in seven patients, polymorphic PTLD in two patients, anaplastic large cell lymphoma in one patient, and Hodgkin lymphoma in one patient. Eighty-four percent of the specimens evaluated for EBV were determined to be positive by in situ hybridization and/or immunohistochemistry. All patients were initially treated with a reduction in immunosuppression therapy, and six patients (55%) received adjuvant chemotherapy. The overall mortality rate was 64%. Four patients died from complications of PTLD (kidney, two patients; heart, one patient; bone marrow, one patient), and three patients (all lung transplant recipients) died from rejection or infectious complications. The median interval from diagnosis to death was 13 months (range, 1 to 42 months). CONCLUSIONS: Thoracic PTLD can occur in any transplant patient and must be regarded as a potentially fatal complication in the immunosuppressed patient. Heart and lung allograft recipients have the worst prognosis because of the mortality that accompanies rejection with subtherapeutic immunosuppression therapy. Earlier diagnosis and improvements in immunosuppression and chemotherapy may improve survival for these inherently high-risk patients.     

Epstein–Barr virus‐associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient

Epstein–Barr virus (EBV) is known to establish latent infections in B‐lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV‐associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post‐transplant lymphoproliferative disorder before the diagnosis of EBV‐PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV‐PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV‐PTSMT are discussed based on a comprehensive review of the literature.     

Mini-BEAM and autologous hematopoietic stem-cell transplant for treatment of post-transplant lymphoproliferative disorders

Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of lymphoid proliferative diseases seen as result of immunosuppression in recipients of solid organ or hematopoietic stem-cell transplantation. Options of treatment include reduction or discontinuation of immunosuppressive agents, antiviral drugs, rituximab, chemotherapy, and radiation. We report two unique cases of PTLD (CNS and plasmacytoma-like) treated successfully with salvage chemotherapy, mini-BEAM chemotherapy, and autologous stem-cell transplant. In both cases, patients were also treated with sirolimus and prednisone as immunosuppression, and neither patient rejected their solid organ transplants. With over 30 months of follow-up, both patients remain in complete remission with excellent allograft function.     

The changing face of adult posttransplant lymphoproliferative disorder: Changes in histology between 1999 and 2013

Posttransplant lymphoproliferative disorder (PTLD) typically presents with either polymorphic or monomorphic histology. While both are the end result of immunosuppressive therapies, their origins are felt to be different with different prognoses and responsiveness to therapy, resulting in 2 different malignancies. We attempted to confirm reports suggesting that the relative frequency of these 2 histologies is shifting over time. We analyzed 3040 adult PTLD cases in the UNOS OPTN database from 1999 to 2013. Changes in PTLD cases over time were analyzed for histology, time from transplant to diagnosis, and patient EBV serostatus. We found that the relative proportion of polymorphic versus monomorphic histology has changed with an increase in the proportion of monomorphic cases with time (1999‐2003, 54.9% vs. 45.1%; 2004‐2008, 58.3% vs. 41.7%; 2009‐2013, 69.7% vs. 30.3%; P = <.001). The change is driven by a gradual increase in the number of monomorphic PTLD with a steady number of polymorphic PTLD. The change is most strongly seen in transplant recipients who were EBV serostatus positive at the time of transplant. Potential causes are changes in immunosuppressive regimens with increased tacrolimus use (P = .009) and increased survival among transplant patients leading to later occurrence of PTLD (P = .001) that have occurred during the time frame analyzed. As organ transplantation has evolved over time, PTLD has coevolved. These changes in histology have important implications regarding the origin and clinical management of PTLD.