Cases Of Post-transplant Lymphoproliferative Disorder Research Articles

Efficacy and safety of valganciclovir in liver-transplanted children infected with Epstein-Barr virus

Epstein-Barr virus (EBV) infection after liver transplantation (LT) is associated with increased risk of posttransplant lymphoproliferative disorder (PTLD). Lowering immunosuppression is the current method to prevent PTLD in LT children with a high viral load. The aim of this study was to assess the efficacy and safety of valganciclovir (VGCV) in children with EBV infection after LT. Forty-seven children showing detectable EBV-DNA (72% asymptomatic) were treated with VGCV (520 mg/sqm twice daily) with no immunosuppression decrease (except in 4 cases). VGCV treatment started 17 months (median) after the onset of EBV infection. A 30-day treatment applied to 26 patients led to undetectable EBV-DNA in 11/32 courses (34.3%), with 82% relapsing. A long VGCV treatment (median: 8 months) achieved undetectable EBV-DNA in 20/42 (47.6%), 60% of whom maintained response off therapy. There were no new PTLD cases. Symptoms worsened in 1 (2.1%) in whom PTLD was suspected but not confirmed in liver and jejunum biopsies. Factors associated with achievement of undetectable EBV-DNA were a longer time from LT and a lower rate of intervening infections in comparison with nonresponders. The safety profile for VGCV was excellent. Graft rejection occurred in 6%. In conclusion, in 47 LT children with a sustained increased EBV load treated with VGCV and unchanged immunosuppression, PTLD was suspected in 1 child (2.1%). A viral load decrease could be achieved as EBV-DNA was undetectable in 47% of patients under prolonged treatment.

Could other viruses cause pediatric posttransplant lymphoproliferative disorder?

Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.

Post-transplant lymphoproliferative disorders of oral cavity

Post-transplant lymphoproliferative disorders (PTLD) are long-term complications of immunosuppression after solid organ/bone marrow transplantation. In most cases, PTLD arises as a result of primary or reactivated Epstein-Barr virus infection in a host with impaired cellular immunity. PTLD is most often seen in the gastrointestinal tract, although it has also been reported in other organ systems, including the central nervous system and, rarely, in the head and neck. It is characterized histologically by abnormal lymphoid cell proliferation. Although many forms of PTLD do not meet all of the histologic criteria of lymphoma, they often behave clinically in a malignant fashion if left untreated. We present 3 rare cases of PTLD manifesting in the oral cavity as mucosal masses after solid organ transplantation. There are only 8 published reports of PTLD in the literature presenting as oral lesions. The clinical, pathologic, and therapeutic spectra of PTLD are discussed.

Post-transplant lymphoproliferative disorder (PTLD) presenting as painful lymphocele 12 years after a cadaveric renal transplant

We report a case of post-transplantation lymphoproliferative disorder presenting as a symptomatic lymphocele 12 years after cadaveric renal transplantation for IgA nephropathy. The presentation, imaging, and management are discussed. We review current literature concerning PTLD, posttransplantation lymphoceles, and state-of-the-art imaging techniques.

A Single-Centre Experience of Clinico-Pathological Features, Risk Factors and Treatment Outcome of Posttransplant Lymphoproliferative Disorders (PTLD) after Renal Transplantation.

Background: PTLD is a lymphoid proliferation that develops as a consequence of immunosuppression and represents monoclonal B-cell, or rarely T-cell proliferations, occurring in a setting of decreased T-cell immune surveillance. PTLD is a major complication after solid organ transplantation. The disease is often unpredictable and devastating of nature resulting in a high rate of morbidity and patient mortality.Methods: Between 1990 and 2005 872 renal transplantations in 793 patients were performed at Skejby University Hospital in Aarhus and 11 cases of PTLD were identified retrospectively. PTLD Patients were investigated according to transplantation procedure, patient characteristics, type of lymphoma, treatment and outcome.Results: 11 of 793 renal transplant recipients (1,4%) developed PTLD. Patients (7 male, 4 female) ranged from 19 to 73 years of age at the time of diagnosis (mean age: 42 years). 8 had a cadaveric renal transplant while 3 received a transplant from related donor. Lymphomas were classified as diffuse large B-cell lymphoma in 10 cases and as Burkitt lymphoma in 1 case. No cases were of T-cell origin or Hodgkins lymphomas. Six cases were EBV positive (54%). Out of 11 cases, 5 were diagnosed within 1 year after transplantation, among which 4 were EBV positive, whereas 6 had a latency period of more than 1 year, among which only 2 were EBV positive. The mean latency time between grafting and diagnosis of PTLD among the early lesions was 7 months and among late lesions 6 years and 2 months (ranging from 1 month to 10 years and 8 months). Sites involved in PTLD were renal graft in 2 cases (both early lesions), lungs in 1 case, bowel system in 4 cases, CNS in 1 case, isolated lymph nodes in 1 case, widespread disease in 1 case and uncertain location in 1 case. All patients were treated by tapering of the immunosuppressive regimen. Two were treated with additional surgery and 3 with chemotherapy - all 5 of them are alive and in complete remission. Among those 5 patients 3 have preserved graft function (60%) and 2 returned to dialysis. One patient was treated with anti-CD20 monoclonal antibody, 3 had both conventional chemotherapy and anti-CD20 immunotherapy and 2 did not receive additional treatment. All 6 were dead at the end of the study period. With a median follow-up period of 5 years and 2 months (ranging from 6 months to 11½ years) 5 patients of 11 PTLD cases (45%) were alive with no sign of lymphoma relapse.Conclusions: PTLD is a severe complication, usually running an aggressive course and the outcome remains poor. The incidence in our population-based regional study material is 1,4%. Overall survival after a median follow-up of 62 months was 45%, with 60% of survivors maintaining graft function.

Efficacy and Safety of Rituximab in Post Transplant Lymphoproliferative Disorders (PTLD): Pooled Analysis and Review of Literature.

PTLD are heterogeneous monoclonal or polyclonal neoplasm usually of B-cell origin with a variable incidence in allogenic bone marrow and solid organ transplant recipients. Due to immunosuppresion in transplant patients, PTLD follows an aggressive course with enhanced treatment-associated toxicity, leading to a overall poor clinical outcome and mortality. Rituximab is a chimeric monoclonal anti-CD20 antibody with known activity in B-cell PTLD and minimal toxicity. A few anecdotal uncontrolled studies and case reports have evaluated the use of rituximab-based therapy for PTLD. In order to define the efficacy and safety of rituximab single agent in the treatment of patients with PTLD we conducted a review of the current available literature and performed a pooled-analysis. We conducted a MEDLINE literature search using Pub med, Ovid software for the key words rituximab, anti-CD20 antibody, PTLD, hematopoetic stem cell transplant (HSCT), solid organ transplant (SOT) and lymphoproliferative disorders on all available published literature analyzed to date (January 1998 to June 30, 2007). Studies involving children (<18 years), individual case reports with less than 5 patients, patients who were treated with chemo-immunotherapy combination were excluded and our search was limited to those PTLD patients treated with rituximab single agent after failure to respond to withdrawal of immunosuppressants. References of each article were also reviewed for additional literature. Studies were also analyzed for duration of PTLD from time of transplantation, rituximab toxicity, and characteristics of responders. A total of 164 peer-reviewed publications were identified after the electronic search using the above keywords. After excluding patients based on above criteria, the pooled-analysis consisted of 308 patients described in 17 reports. Diagnosis of PTLD cases was based on histological examination and World Health Organization classification. Among the 17 reports, 3 studies included HSCT patients with n=24; the rest consisted of SOT patients. The mean age of the patients was 57; PTLD classified as late onset (>1 year) in most patients (∼70%). Rituximab was used as first line therapy after failure of immunosuppression withdrawal, and patients were initially treated with four weekly doses of rituximab at 375mg/m2. Rituximab was continued as maintenance therapy in responding patients in few studies. The complete response rate (International Workshop Criteria) was 58% (29%–78%), among SOT patients and 70% (66%–83%) among HSCT patients. Side effects were minimal and no treatment related deaths were attributed to rituximab. Long term follow up from 2 prospective studies demonstrate a durable remission in 30%–37% SOT patients at 5 years. Limited evidence exists for optimal treatment approach in PTLD. Clinical heterogeneity among small number of patients diagnosed makes it difficult to conduct randomized prospective studies in this disorder. Our study is the first pooled analysis evaluating the role of rituximab in PTLD. Minimal toxicity with good efficacy favors rituximab's use among patients with less aggressive PTLD who fail or unable to tolerate withdrawal of immunosuppression.

Gene Expression Profiling of Epstein-Barr Virus-positive and -negative Monomorphic B-cell Posttransplant Lymphoproliferative Disorders

Although most posttransplant lymphoproliferative disorders (PTLD) are related to Epstein-Barr virus (EBV) infection, approximately 20% lack detectable EBV (EBV-). It is uncertain whether the latter cases are truly distinct from EBV+ PTLD or possibly relate to another infectious agent. This study used gene expression profiling to further investigate the relationship between EBV+ and EBV- monomorphic B-cell PTLD, and to search for clues to their pathogenesis. Affymetrix HU133A GeneChips were used to compare 4 EBV+ and 4 EBV- cases of monomorphic B-cell PTLD. Hierarchical clustering successfully distinguished the EBV+ and EBV- groups. Relative to EBV- PTLD, 54 transcripts were over-expressed in EBV+ PTLD. The transcripts identified included IRF7 (a known regulator of EBV LMP1 expression), EBI2 (EBV-induced gene 2), and 3 that are interferon induced (MX1, IFITM1, and IFITM3). In addition, the EBV+ group contained 232 transcripts decreased relative to the EBV- group, including changes concordant with those previously reported after EBV infection of cultured B-cell lines. In summary, in a small group of monomorphic B-cell PTLD, EBV+ cases demonstrated a subset of gene expression changes associated with EBV infection of B cells. By contrast, EBV- PTLD lacked viral-associated changes suggesting that they are biologically distinct.

Posttransplant Lymphoproliferative Disorders After Liver Transplantation: Analysis of Early and Late Cases in a 255 Patient Series

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.

Adolescents Are More Likely to Develop Posttransplant Lymphoproliferative Disorder After Primary Epstein-Barr Virus Infection Than Younger Renal Transplant Recipients

Primary Epstein-Barr virus (EBV) infection is the most important risk factor for development of posttransplant lymphoproliferative disorder (PTLD). Pediatric patients are often EBV seronegative pretransplant placing them at high risk. In the immune-competent population, primary herpesvirus infection is associated with higher morbidity with increasing age. We performed a retrospective cohort study to describe the outcome of pediatric renal transplant recipients with primary EBV infection. All patients received 3 months of ganciclovir prophylaxis. Real-time quantitative polymerase chain reaction was used to determine the EBV viral load. Primary EBV infection was categorized as PTLD, symptomatic infection, or subclinical infection. There were a total of 46 patients with primary EBV infection: 11 developed PTLD, 12 had symptomatic infection, and 23 had subclinical infection. Adolescents were significantly more likely to develop PTLD than younger transplant recipients (P=0.05, chi-square). Multivariate analysis using logistic regression found that older age was the only significant risk factor for PTLD (odds ratio 1.24, 95% confidence interval 1.04-1.47; P=0.03). Among the 11 cases of PTLD, there were two deaths and two graft failures which all occurred in adolescent recipients (P=0.002). Among pediatric renal transplant recipients with primary EBV infection, adolescents are at significantly higher risk to develop PTLD and have poorer outcomes compared to younger recipients.

骨髄移植後に口腔粘膜にみられた移植後リンパ球増殖症の１例

骨髄移植後に口腔粘膜にみられた移植後リンパ球増殖症の１例

Posttransplantation lymphoproliferative disorder—The great mimic in liver transplantation: Appraisal of the clinicopathologic spectrum and the role of Epstein-Barr virus

Case series describing posttransplantation lymphoproliferative disorder (PTLD) after liver transplantation (LTx) have been limited in number because of the rarity of the disorder. The prevalence of Epstein-Barr virus (EBV) infection and its detection, the clinical and histological diversity of disease, and survival have varied. The aim of this study is to define the clinical and pathological spectrum of PTLD after LTx, and evaluate EBV prevalence, impact of infection, and patient survival. A retrospective analysis of all LTx recipients at our institution diagnosed with PTLD from January 1990 until May 2005, recording clinical presentations, times of presentation after transplantation, histological findings, results of EBV assessment, and survival, as well as the interrelationship of these variables. Among 621 LTx recipients were 22 cases of PTLD in 21 patients, of whom 5 were children and 16 were adults. Extranodal disease was present in 17 of 22 cases (77%) involving a wide variety of organ systems, while 5/22 (23%) had lymphadenopathy. The spectrum of PTLD histopathology was equally varied. In situ hybridization for EBV showed negativity in 8 of 13 (62%) and positivity in 5 of 13 (38%) cases tested. Neither time interval from transplantation to presentation (median 33 months) nor mortality (average 32%) was influenced by EBV status. In conclusion, PTLD in LTx recipients is predominantly extranodal and can involve a wide variety of organ systems, which may confound initial diagnosis. The lymphoproliferative histological spectrum is also diverse. Nowadays, PTLD is frequently EBV-negative, and EBV status does not appear to influence clinical or pathological presentation, or survival.

Posttransplant lymphoproliferative disorder in adult liver transplant recipients: A report of seventeen cases

Posttransplant lymphoproliferative disorder (PTLD) is a major complication of liver transplantation, but previous descriptions have been limited to case reports and small case series. We report a retrospective analysis of 17 consecutive cases of PTLD associated with liver transplantation. The median age at PTLD diagnosis was 47 years (range 19 – 63) with a median time of 25 months from liver transplantation to PTLD diagnosis (range 3 – 75). PTLD location was frequently extranodal (71%) and involved the transplanted liver (41%). PTLD histology consisted of nine (53%) monomorphic and eight (47%) polymorphic disease. EBV was present by in situ hybridization in 11 (79%) of 14 cases evaluated. Initial therapy included reduction in immunosuppression (RI) alone in 13 (76%) of 17 patients, resulting in 6 (46%) complete responses (CR) and 7 (54%) progressive disease (PD). Monoclonal CD20 antibody (rituximab) and CHOP chemotherapy were used as initial therapy or as second line after RI failure. Currently, five patients (29%) are alive in CR. Although detection and treatment of PTLD in liver transplant recipients remains problematic and upfront mortality is still high, long-term survival is possible. Further studies are necessary to better define treatment strategies.

Lymphoproliferative disorder presenting as a tumor of the renal allograft

Post-transplant lymphoproliferative diseases (PTLDs) constitute a group of potentially life-threatening complications in solid organ transplantation, occurring in 1-2% of kidney transplant recipients. The absolute number of cases occurring at each transplant center remains small, making it difficult to assess incidence, prognosis, and treatment. We report a case of post-transplant lymphoproliferative disorder that developed in the allograft renal parenchyma 2 years after renal transplantation. This case implies that partial nephrectomy may be a safe and effective treatment protocol for renal lymphoma in allograft kidneys.

Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion

Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)-like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD.

Autologous Hemopoietic Stem Cell Transplantation Is a Viable Treatment Option for Post Liver Transplant Lymphoproliferative Disorder: A Case Report.

Post-transplant lymphoproliferative disorders (PTLD) are B-cell disorders characterized by abnormal lymphoid proliferation due to immunesuppression mediated T-cell dysfunction after organ transplantation, and carry a poor prognosis. Reduction of immunesuppression is the first line of therapy but involves the risk of allograft rejection. Anti-viral agents like acyclovir, intravenous immunoglobulin, interferon-α, anti interleukin -6 antibodies, chemotherapy and rituximab are other treatments that have been tried with limited success. EBV-specific adaptive immunetherapy is promising but only available in a few centers. Prognosis is poorer in patients with relapsed disease. We report the case of a 46 year-old liver transplant recipient, with recurrent PTLD after liver transplantation, who was successfully treated with high dose chemotherapy followed by autologous bone marrow transplant (ABMT). He had undergone an orthotopic liver transplant (OLT) 13 years ago for primary sclerosing cholangitis. PTLD (EBV related, Hodgkin like, CD20+ and CD30+) developed 7 years ago, and initially resolved with ganciclovir and reduction of immunesuppression. The patient relapsed 5 years later. Immunesuppression was discontinued and 3 cycles of rituximab with CHOP (R-CHOP) followed by 4 doses of R at weekly intervals were given leading to complete response. Four months later, he again relapsed and responded to 4 more cycles of R-CHOP. He was referred to our center for transplant evaluation. Progenitor cell mobilization with filgrastim was unsuccessful. He underwent an unstimulated bone marrow harvest yielding 1.02 × 10 6 CD34 cells/kg. Transplant conditioning was with R-BEAM. Because of abnormal liver function tests and concern for further hepatotoxicity, carmustine dose was reduced by 50%. Immunesuppression for OLT was withheld during the transplant period. He tolerated the chemotherapy well but had delayed neutrophil and platelet engrafment (days +31 and +50 respectively). Liver functions deteriorated in the post transplant period, but responded to reinitiation of prednisone and tacrolimus on days +41 and +50, respectively. Post transplant PET/CT imaging performed on day+45 revealed complete resolution of his lymphadenopathy. He continues to be asymptomatic with no evidence of relapse days+ 72 after transplant, at the time of this writing. ABMT is the standard of care for chemotherapy-sensitive relapsed lymphomas. However, the complexity of ABMT after a prior solid organ transplant limits its use for relapsed PTLD. There is a higher likelihood of regimen-related toxicity, and immunesuppression needs to be carefully managed. While it is desirable to reduce immunesuppression during the transplant period to minimize infections and to control PTLD, this has to be balanced against the risk of solid organ graft rejection. This is particularly critical in patients with liver transplantation in whom (unlike renal graft) loss of liver graft may be fatal. There are only 6 previous cases of PTLD treated with stem cell transplant, but none of these patients had a prior OLT. Our experience with this case suggests that autologous bone marrow transplant can be a potential treatment option for patients with recurrent PTLD in selected patients. Appropriate dose modification of conditioning regimen and careful management of peritransplant immunesuppression appears important for successful outcome.

High Incidence of Posttransplant Lymphoproliferative Disorder after Unrelated Cord Blood Transplantation.

Though posttransplant lymphoproliferative disorder (PTLD) is a well-documented complication arising in recipients of solid organ or hematopoietic stem cell transplantation, data about PTLD following cord blood transplantation (CBT) are limited. Currently less than 20 cases of PTLD have been described after CBT in the literature world-wide. However, we hypothesized that several factors such as relatively lower number and naïve nature of cord blood T-lymphocytes, frequent donor-recipient HLA disparity and in vivo T-cell depletion by ATG might lead unrelated cord blood recipients more susceptible to PTLD. We retrospectively reviewed the medical records of 45 pediatric recipients who received unrelated CBT at our institution from Jan 2002 to Jan 2006. At least 4/6 matched cord blood units were selected for transplant and some patients (n=10) received double cord blood units. ATG was included in the preparative regimen in all but one case. Cyclosporine with either methyl-prednisolone or mycophenolate mofetil were used for GvHD prophylaxis. We assessed the cumulative incidence, clinical features, pathologic findings, and treatment results of PTLD after unrelated CBT. Only pathologically proven cases were included for analysis. Five patients developed PTLD at 3 to 8 mo posttransplant (median, 4 mo). The cumulative incidence of PTLD was 14.1% at 2 year estimated by Kaplan-Meier method. Four of the 5 patients were positive for EBV serology before transplant. The involved sites were variable such as lymph nodes, brain, lung, liver, kidney, parotid gland, and colon. Three patients had multiple sites of PTLD involvement. Biopsied samples of 5 patients revealed diffuse CD20 positivity (n=4), positive for EBV in situ hybridization and/or EBNA/LMP (n=4), monomorphic (n=2), and polymorphic (n=3) histology. One patient had lesions showing diffuse CD3 positivity instead of CD20 suggesting T-PTLD. Two patients with monomorphic disease were cured with rituximab therapy and 2 of 3 with polymorphic PTLD became free of disease after immune withdrawal. The other one with polymorphic B-PTLD underwent progressive course despite immune withdrawal and rituximab therapy. In conclusion, the incidence of PTLD after unrelated CBT in this study was much higher than previously reported. Clinical suspicion and thorough diagnostic work-up followed by early therapeutic intervention should be given not to miss the potentially curable disease.

The Impact of the World Health Organization Classification and Clonality Assessment of Posttransplant Lymphoproliferative Disorders on Disease Management

The World Health Organization classification of posttransplant lymphoproliferative disorders divides them into 4 main categories. To classify cases of posttransplant lymphoproliferative disorders diagnosed in our institution according to the World Health Organization scheme and correlate the classification and clonality with clinical data. Cases of posttransplant lymphoproliferative disorders were reviewed. They were classified according to the World Health Organization scheme. Clonality was determined by flow cytometry and/or polymerase chain reaction. Patients' charts were reviewed. Thirty-one cases were identified. Median age was 33 years. There were 19 cases of kidney, 8 cases of liver, and 4 cases of bone marrow transplant. Immunosuppression consisted of cyclosporin A and prednisone (N = 24) or FK506 and prednisone (N = 7). Twenty cases (63%) were World Health Organization type 3, 7 cases (23%) type 2, 3 cases (6.4%) type 1, and 1 case type 4 posttransplant lymphoproliferative disorder. Ten patients received chemotherapy, 20 patients had reduction of immunosuppression, and 1 had no treatment. Follow-up was available on 25 patients. Seven (43.75%) of 16 with type 3 lesions with available follow-up died of their disease. Five of these patients received reduction of immunosuppression alone. Only 2 of 9 patients with type 3 disease who received chemotherapy died of disease. Two patients with type 2 disease died of unrelated causes. One patient is alive with disease; the remaining patients with types 1 and 2 disease are alive with no disease. The World Health Organization classification of posttransplant lymphoproliferative disorders is valuable in the identification of subtypes. It helps identify early lesions (1 and 2) requiring reduction of immunosuppression and type 3 disease, which requires chemotherapy from the outset.

Post-Transplant Lymphoproliferative Disorders Occurring After Renal Transplantation in Adults: Report of 230 Cases From the French Registry

Post-transplant lymphoproliferative disorders (PTLD) are a rare but serious complication after organ transplantation. A French Registry of PTLD was set up in a nationwide population of kidney transplant recipients. We prospectively enrolled all adult kidney recipients developing PTLD between January 1, 1998, and December 31, 2003. We analyzed the incidence, risk and prognostic factors of PTLD by Kaplan-Meier and Cox analyses. Totally 230 cases of PTLD were referred to the French Registry. Cumulative incidence was 1.18% after 5 years. Older age (per year, AHR = 2.19, CI = 1.22-3.94) and recipient Epstein-Barr virus seronegativity (AHR = 3.01, CI = 1.57-5.08) were associated with an increased risk of PTLD. Patients with PTLD had a reduced survival rate (61% at 5 years). Graft PTLD had the best prognosis with an 81% survival rate after 5 years. Infection with hepatitis C or B virus (HCV or HBV), late-onset PTLD, multiple sites involvement and high Ann Arbor staging were risk factors for patient death. Use of azathioprine was associated with a poorer survival rate. PTLD incidence and risk factors in French recipients are in line with the international or American PTLD series. We highlighted the role of HBV or HCV in patient mortality and described the relevant prognosis factors for patients with post-transplant lymphoproliferations.

Treatment and outcomes of post‐transplant lymphoproliferative disease: A single institution study

Post-transplant lymphoproliferative disorders (PTLD) complicate up to 10% of solid organ transplants. This retrospective study was conducted to review the PTLD experience among 2,300 recipients of solid organ or allogeneic bone marrow transplants from a single institution. Twenty-seven cases of PTLD were identified, leading to an overall incidence of 1.2%. Polymorphic B cell hyperplasia/lymphoma was the most common type. The median time to development of PTLD was 8.4 months. Ten patients had localized (stage I or II) disease, and 12 patients presented with B symptoms. Nine patients each were treated with systemic chemotherapy or surgical resection as part of the initial therapy. After a median follow-up duration of 2.6 years, the median survival has not been reached. There were no late relapses of PTLD, and 17 patients remain alive. Age, sex, organ source, LDH, stage, presence of extranodal disease, or presentation with B symptoms did not influence overall survival when examined by Cox proportional hazard model. Thirteen patients retained their graft function throughout PTLD treatment. This study confirms the ability to treat a significant proportion of PTLD patients with chemotherapy or surgical resection (depending on presentation), without sacrificing graft function in those receiving chemotherapy.

Muromonab-CD3 (Orthoclone OKT3®), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation

We report the results of a prospective non-randomized phase II study of Muromonab-CD3 (Orthoclone OKT3), an anti-CD3 monoclonal antibody, with methylprednisolone (MP) and cyclosporine (CSA) for acute GVHD (aGVHD) prophylaxis in 22 hematologic malignancy patients. OKT3 was given at 0.1 mg/kg/day with a maximum dose of 5 mg/day. Initial MP dose was 1000 mg before OKT3, with subsequent doses at 1 mg/kg/day before each OKT3 infusion with a planned taper beginning at day +28. CSA (3 mg/kg/day) was given as a continuous infusion at day -1 and adjusted to maintain serum levels between 250 and 399 ng/ml. Allogeneic BMT donors were HLA-matched siblings (n = 17), single HLA-mismatched-related (n = 1) and HLA-matched unrelated (n = 4). All patients achieved neutrophil engraftment at a median 11 days (range, 8-25 days). By intent-to-treat, the cumulative incidence of grade II-IV aGVHD was 33% (95% CI 13-53%) at a median 26 days post-BMT (range, 14-84 days). Chronic GVHD developed in 11/12 evaluable patients. Eight patients (36%) developed OKT3 first dose reactions; no cases of post-transplant lymphoproliferative disorder were observed. OKT3 depleted peripheral CD3+ cells in vivo as measured by flow cytometry. OKT3+MP+CSA combination is moderately effective aGVHD prophylaxis, however, it is unlikely to be superior to CSA+MTX.