Epstein-Barr Virus-associated Post-transplant Lymphoproliferative Disorder Research Articles

Outcomes of children treated for multiple Epstein-Barr virus-associated post-transplant tumors.

After solid organ transplantation, children are at risk for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. Little is known about the clinical course, Epstein-Barr viral load variations, and optimal treatment for such patients. We set forth to understand the course of repeated episodes of post-transplant lymphoproliferative disorder and smooth muscle tumors. We performed a retrospective chart review of patients up to 21 years old with solid organ transplantation and post-transplant lymphoproliferative disorder at the Children's Hospital of Philadelphia from January 2003 through June 30, 2020. Six patients had multiple episodes of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. When the second episode was discovered, only one patient was symptomatic. Histology differed from diagnosis in four patients. Treatment included viral-specific T-lymphocytes (2), rituximab (3), reduction in immunosuppression alone (1). Five patients had complete response, and one had stable disease, but three patients developed a subsequent tumor. Two patients developed Epstein-Barr virus-associated smooth muscle tumors. Of these six patients, four are alive. The deaths were not related to their tumors. Despite a complete response to initial therapy, children are at risk for repeated episodes of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and smooth muscle tumors. Histology and location were not typically consistent with initial diagnosis, suggesting these are second primaries rather than recurrences. Disease may be managed with individualized treatment plans but EBV-specific T cells need further study in such tumors.

Idiopathic Pulmonary Fibrosis Lung Transplant Recipients are at Increased Risk for Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorder

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single-center retrospective study to evaluate the risks for PTLD in LTRs over a seven-year period. All LTRs transplanted from 2010 to 2016 were included. LTRs who died within 3 months or were lost to follow-up were excluded. Sex, age, EBV serostatus, induction agent, indication agent, and survival were collected via chart review. The primary outcome was development of PTLD. Secondary endpoints were early and late PTLD and survival. Primary and secondary outcomes were assessed using Kaplan-Meier methods and Cox proportional hazards models. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed an increased rate of PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (p<0.02). Multivariable Cox proportional hazards modeling found IPF (HR 3.51, 95% CI 1.33-8.21, p=0.01), alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, p=0.03), and EBV mismatch (HR: 34.43, 95% CI: 15.57-76.09, p<0.0001) as risk factors for PTLD. Early PTLD (first-year) was associated with alemtuzumab use (p=0.04), whereas IPF was a predictor for late PTLD (after first-year) (p=0.002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF-LTRs compared to other LTRs (p=0.04). The use of alemtuzumab in EBV-mismatch was found to particularly increase PTLD risk. IPF-LTRs are at increased susceptibility for PTLD compared to non-IPF LTRs. LTRs who received alemtuzumab induction were at increased risk for PTLD, particularly those who were EBV mismatches. Ongoing studies are being conducted to understand the mechanisms driving PTLD in IPF-LTRs and develop strategies to mitigate risk.

Repeat Endoscopy Affects Patient Management in Gastrointestinal Graft-Versus-Host Disease

Graft versus host disease (GVHD) of the gut is associated with significant morbidity and mortality after allogeneic hematopoietic cell transplant (allo-HCT). No guidelines exist regarding repeat endoscopy after failure of first-line treatment with steroids. We aimed to study if repeat endoscopic biopsy can be helpful in these patients to guide treatment decisions. We retrospectively reviewed medical records of all patients who underwent repeat endoscopy for clinical suspicion of gastrointestinal (GI) GVHD after allo-HCT. Of the 318 patients, 24 underwent endoscopy twice after allo-HCT. At first endoscopy, 20 patients (80%) showed abnormal findings: 16 with GVHD alone, 1 with GVHD plus Cytomegalovirus (CMV), and 3 with GVHD plus infectious colitis. On repeat endoscopy in these 20 patients with GVHD, 6 showed improvement leading to de-escalation of therapy, 8 showed worsening of GVHD including detectionof CMV in 2 patients, and 2 hadno histological changes. One patient with simultaneous GVHD and CMV diagnosed on first biopsy, displayed significant improvement leading to de-escalation of therapy. Three patients with GVHD along with infectious colitis on biopsy subsequently showed improvement on repeat biopsy leading to de-escalation of therapy. Among 4 patients with normal findings on first endoscopy, 3 had GVHD and 1 had epstein-barrvirus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) on repeat procedures. This study supports the usefulness of repeat endoscopy in persistently symptomatic patients when there is no improvement after the initial treatment based on the results of the first endoscopy. Repeat endoscopy may guide therapy without significant complications.

Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival.

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (EBV-PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single-center retrospective study to evaluate the risks for PTLD in LTRs over a 7-year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (P<.02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33-8.21, P=.01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, P=.03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57-76.09, P<.0001). Early PTLD (first year) was associated with alemtuzumab use (P=.04), whereas IPF was a predictor for late PTLD (after first year) (P=.002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P=.04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorder revealed by autopsy

Epstein-Barr virus-associated post-transplant lymphoproliferative disorder revealed by autopsy

Rapamycin ameliorates the CTLA4-Ig–mediated defect in CD8+ T Cell Immunity During Gammaherpesvirus Infection

Latent viral infections are a major concern among immunosuppressed transplant patients. During clinical trials with belatacept, a CTLA4-Ig fusion protein, patients showed an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder, thought to be due to a deficient primary CD8(+) T cell response to the virus. Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus-specific CD8(+) T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4-Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen-specific CD8(+) T cells. However, the addition of rapamycin to the CTLA4-Ig regimen was able to quantitatively and qualitatively restore the antigen-specific CD8(+) T cell response to the virus. This improvement was physiologically relevant, in that CTLA4-Ig treated animals exhibited a greater viral burden following infection that was reduced to levels observed in untreated immunocompetent animals by the addition of rapamycin. These results reveal that modulation of T cell differentiation though inhibition of mTOR signaling can restore virus-specific immune competence even in the absence of CD28 costimulation, and have implications for improving protective immunity in transplant recipients.

Epstein-Barr virus-associated posttransplant lymphoproliferative disorder after allogeneic stem cell transplantation.

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder is an increasingly life-threatening complication after allogeneic stem cell transplantation with the use of more complex transplant procedures. Reduced intensity conditioning regimens in combination with in-vivo or ex-vivo T-cell depletion are particularly important risk factors. Prospective monitoring of EBV viremia by real-time quantitative polymerase-chain reaction (PCR) should be performed after high-risk allogeneic stem cell transplantation. However, lack of standardization and concerns about sensitivity and low positive-predictive value challenge the interpretation of PCR monitoring. Preemptive treatment is feasible and can reduce EBV-related mortality but may lead to overtreatment in some patients. Readily available rituximab and methods of adoptive transfer of T-cells are valuable tools. Rituximab is probably the most attractive agent showing the most robust data in this setting. Rituximab seems to offer a good balance between efficacy and toxicity for the treatment of established EBV-associated posttransplant lymphoproliferative disorder. But most often there is a need to combine with adoptive immunotherapy with T-cells to maintain long-term disease control, with either simple unmanipulated donor lymphocyte infusion or more specific and complex adoptive EBV-specific cytotoxic T-cells. EBV-associated posttransplant lymphoproliferative disorder can often be prevented or treated, especially in earlier stages. The specific role and timing of the different treatment strategies need to be defined.

Epstein-Barr virus-associated posttransplant lymphoproliferative disorder involving the central nervous system following autologous hematopoietic stem cell transplantation for neuroblastoma.

IntroductionPosttransplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ or hematopoietic stem cell transplantation (HSCT). Although extranodal involvement of PTLD is common, its isolated involvement in the central nervous system (CNS) is extremely rare. To date, primary CNS-PTLD has been reported in 13 patients who underwent allogeneic HSCT, but no cases have been reported in autologous HSCT recipients.Case DescriptionHerein, we report the first report of a patient with neuroblastoma that progressed to CNS-PTLD after autologous peripheral blood stem cell transplantation (auto-PBSCT). A 27-month-old boy with stage IV neuroblastoma of the left adrenal gland received auto-PBSCT after intensive chemotherapy, tumor resection, and radiation of tumor bed and regional lymph node. An intracranial tumor in his left parietal lobe was detected by magnetic resonance imaging 99 days posttransplantation, and the tumor was completely resected. The histological diagnosis of the intracranial tumor was diffuse large B-cell lymphoma with latency type III Epstein-Barr virus infection. The patient has maintained tumor free status 3 years after auto-PBSCT.Discussion and EvaluationGiven the rarity of CNS-PTLD, there is no consensus on the optimal treatment. Historically, the outcome of CNS-PTLD has been very poor. However, our patient remains free from PTLD after only total resection. The prognosis for PTLD following auto-HSCT may depend upon the underlying malignancy, immune state, EBV immune status, and treatments.ConclusionsThe outcome of PTLD following auto-HSCT is not necessarily poor prognosis. Further research is required to establish the optimal treatment strategy for CNS-PTLD.

The emergence of CD20−/CD19− tumor cells after rituximab therapy for Epstein–Barr virus-associated post-transplant lymphoproliferative disorder complicated with hemophagocytic lymphohistiocytosis

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized aggressive disease commonly associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although rituximab (RTX) is incorporated into the first-line therapy for EBV-PTLD patients, the outcome of the clinically overt disease is still not optimal mainly due to the regrowth of tumor cells. The proliferation of CD20-/CD19+ tumor cells is increasingly reported in RTX-treated EBV-PTLD patients, whereas the emergence of CD20-/CD19- tumor cells is barely recognized. Here, we report a fatal case of an 18-year-old patient who developed EBV-PTLD after allogeneic HSCT for anaplastic large-cell lymphoma. On day 60 after HSCT, the patient developed abdominal pain, watery diarrhea, and low-grade fever. Colon biopsy revealed the proliferation of CD20+/CD19+/EBV-encoded RNA (EBER)+ tumor cells, and an increase of EBV DNA was detected in peripheral blood (PB). He was treated with RTX for EBV-PTLD and was cleared of EBV DNA in PB. However, he manifested high-grade fever, pancytopenia, and elevated soluble interleukin-2 receptor with a prominent hemophagocytosis in bone marrow aspirates and was treated with etoposide for hemophagocytic lymphohistiocytosis (HLH) complication. He then developed EBV DNA positivity in PB and finally died of Bacteroides fragilis sepsis subsequent to bloody stool and ileus on day 163. Autopsy revealed erosion and bleeding in the whole colon with the proliferation of CD20-/CD19-/EBER+ tumor cells. Immunohistochemical analysis uncovered the CD3-/CD56-/CD79a+/CD79b+ B-cell origin of tumor cells. This case clinically demonstrates the removal of both CD20 and CD19 antigens from EBER+ B cells in an RTX-treated EBV-PTLD patient with HLH complication.

Epstein–Barr virus-associated post-transplant lymphoproliferative disorders after allogeneic peripheral blood stem cell transplantation for Hodgkin-like adult T-cell leukemia/lymphoma

A 56-year-old woman with Hodgkin-like adult T-cell leukemia/lymphoma was treated with allogeneic peripheral blood stem cell transplantation on 17 April 2009. She manifested a moderate fever on day 41. CT scanning and other examinations detected slightly swollen lymph nodes, and pathological findings of right axillary lymph nodes revealed an Epstein-Barr virus-associated post-transplant lymphoproliferative disorder. She was successfully treated with rituximab.

Isolated cerebral manifestation of Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: a case of clinical and diagnostic challenges

We present the case of a 49-year-old male patient with Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) limited to the brain that occurred 6 months after allogeneic hematopoietic stem cell transplantation (HSCT). Clinical symptoms included mental confusion, ataxia, and diplopia. Magnetic resonance imaging (MRI) revealed cerebellar and periventricular lesions consistent with an inflammatory process. Cerebrospinal fluid (CSF) analysis, but not peripheral blood, was positive for EBV-DNA, but no malignant cells were found. Brain biopsy was not feasible because of low platelet counts. As we considered a diagnosis of either EBV-associated encephalitis or PTLD, the patient was treated with rituximab combined with antiviral therapy. However, the cerebral lesions progressed and follow-up CSF testing revealed immunoglobulin H clonality as evidence of a malignant process. Subsequent treatment attempts included 2 donor lymphocyte infusions (DLI). Despite treatment, the patient died from autopsy-proven PTLD within 8 weeks of the onset of symptoms. This case demonstrates the clinical and diagnostic challenges of primary cerebral PTLD in a patient following allogeneic HSCT.

同種造血幹細胞移植後の小腸穿孔で診断されたEpstein-Barr virus関連移植後リンパ増殖性疾患

同種造血幹細胞移植後の小腸穿孔で診断されたEpstein-Barr virus関連移植後リンパ増殖性疾患

Isolated central nervous system Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorder

Pediatric Blood & CancerVolume 56, Issue 5 p. 871-872 Letter to the Editor Isolated central nervous system Epstein–Barr virus-associated post-transplant lymphoproliferative disorder Akihiro Watanabe MD, Corresponding Author Akihiro Watanabe MD aki-wata@niigata-cc.jp Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanDepartment of Pediatrics, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan.===Search for more papers by this authorSakiko Yoshida MD, Sakiko Yoshida MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorYasushi Kasahara MD, Yasushi Kasahara MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorTakayuki Takachi MD, Takayuki Takachi MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorAtsushi Ogawa MD, Atsushi Ogawa MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorKeiko Asami MD, Keiko Asami MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this author Akihiro Watanabe MD, Corresponding Author Akihiro Watanabe MD aki-wata@niigata-cc.jp Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanDepartment of Pediatrics, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan.===Search for more papers by this authorSakiko Yoshida MD, Sakiko Yoshida MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorYasushi Kasahara MD, Yasushi Kasahara MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorTakayuki Takachi MD, Takayuki Takachi MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorAtsushi Ogawa MD, Atsushi Ogawa MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this authorKeiko Asami MD, Keiko Asami MD Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, JapanSearch for more papers by this author First published: 28 November 2010 https://doi.org/10.1002/pbc.22910Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume56, Issue5May 2011Pages 871-872 RelatedInformation

Post-transplant lymphoproliferative disorder involving the ovary as an initial manifestation: a case report

IntroductionBecause the normal ovary is assumed to be devoid of lymphoid tissue, it is unusual for it to be an initial manifestation of malignant lymphoma. This case is the first report, to our knowledge, of post-transplant lymphoproliferative disorder involving the ovary as an initial manifestation.Case presentationTwenty-nine weeks after a living renal transplantation, a 38-year-old Japanese female, whose ethnic origin was Asian, presented with abdominal pain and a chronic high fever. Computed tomography revealed a right ovarian tumor and liver metastases. The patient underwent oophrectomy based on the clinical diagnosis of liver metastasis from the primary ovarian tumor. The pathological diagnosis was Epstein-Barr Virus-associated post-transplant lymphoproliferative disorder. While ovarian malignant lymphoma has a poor prognosis, complete remission of liver involvement in this case was achieved only with a reduction of immunosuppressants.ConclusionClinicians should remember that malignant lymphoma could initially involve the ovary, especially if the patient is immunosuppressed after transplantation therapy.

Cytomegalovirus and Epstein–Barr virus-associated post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation

Cytomegalovirus and Epstein–Barr virus-associated post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation

Increased Risk of Epstein-Barr Virus Associated Post-Transplant Lymphoproliferative Disorder (EBV-PTLD) after Anti-Thymocyte Globulin (ATG) Non-Myeloablative (NMA) Conditioning for Umbilical Cord Blood Transplantation (UCBT).

EBV-PTLD is a known complication of alternative donor hematopoietic stem cell transplantation (HSCT) particularly when used in combination with HSC T-cell depletion and ATG. Initial reports in the setting of UCBT suggested a low incidence of EBV-PTLD (2–5%). We reviewed 335 consecutive patients (pts) who underwent UCBT at our institution between 7/19/94 and 3/29/05. Median age, weight, and follow-up were 16 years (0.2–69), 53.7kg (3.8–134.0) and 1.2 years (77 days9.2 years), respectively. Equine ATG (ATGAM) was used as part of a myeloablative (MA, Cy 120 mg/kg and TBI 1320–1375 cGy ± Flu 75 mg/m2) and non-myeloablative (NMA, Cy 50 mg/kg, Flu 200 mg/m2 and TBI 200 cGy) preparative regimen in 175/240 and 30/95 patients, respectively. As previously reported the overall incidence of EBV viremia and EBV-PTLD remained low. Overall, use of ATG lead to an increase in the incidence of EBV viremia (defined as > 1,000 copies of EBV DNA per mL of whole blood) and EBV-PTLD (14/205 [7%] with vs. 1/130 [0.7%] without ATG [p=0.16]), but this was not statistically significant. In recipients of a MA preparative regimen, EBV viremia or EBV-PTLD was observed in 8/175 (5%) who received ATG and in 0/65 who did not (p=0.81). However, a higher risk of EBV viremia and PTLD was observed in recipients of ATG and a NMA preparative regimen. EBV viremia or EBV-PTLD after NMA preparative regimen was observed in 6/30 (20%) pts who received ATG and 1/65 (2%) who did not (p<0.01) For the whole group, median time to development of EBV-PTLD was 133 days (54–407) with no difference between the MA and NMA groups [132 days (92–407) vs. 133 days (54–247)]. Among 9 pts who developed EBV-PTLD, 5 are alive (2 MA and 3 NMA) 113-1668 days after UCBT. Therefore, we conclude that patients undergoing a NMA UCBT with ATG are at uniquely higher risk for the development of EBV reactivation or EBV primary infection and EBV-PTLD. Routine monitoring of EBV viral load and pre-emptive treatment of patients who develop a positive viral load must be considered for this group of patients.

Determination of risk factors for Epstein-Barr virus-associated posttransplant lymphoproliferative disorder in pediatric liver transplant recipients using objective case ascertainment.

Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD. Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression. Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%-14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21-7.92), as was age at transplantation as a continuous variable (parameter estimate -0.15, P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54-0.93) and 0.54 (95% CI: 0.40-0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases. Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.

Recurrent epstein-barr virus-associated post-transplant lymphoproliferative disorder: Report of a patient with histologically similar but clonally distinct metachronous abdominal and brain lesions

A liver transplant patient developed a single central nervous system (CNS) intraparenchymal lesion 5 months after the diagnosis of an intraabdominal diffuse large B-cell post-transplant lymphoproliferative disorder (PTLD). Biopsy of the new CNS lesion showed a diffuse large B-cell PTLD morphologically and immunohistochemically indistinguishable from the abdominal lesion. In addition, both lesions were positive for Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR) and for EBV-encoded RNA by in situ hybridization. Although these results were consistent with a metastatic origin for the CNS lesion, the finding of an intraparenchymal lesion without leptomeningeal or dural spread was suggestive of a new primary CNS lymphoma. Proof that the brain lesion was a second primary and not a metastasis was obtained by immunoglobulin gene rearrangement studies and assessment of EBV clonality. Multiple primary lymphoid neoplasms arise at higher frequency in the setting of immunosuppression, and molecular investigations of tumor clonality can provide clinically relevant staging and prognostic information.

Analysis of the complications of the piggy-back technique in 1112 liver transplants: Surgical technique

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