Improved Survival with Recent Post‐Transplant Lymphoproliferative Disorder (PTLD) in Children with Kidney Transplants

Post‐transplant lymphoproliferative disorder (PTLD) has been associated with high mortality, but recent anecdotal survival appeared better. From 1988 to 2010, the NAPRTCS registry had 235 registered PTLD cases. We sent a special 25‐point questionnaire study to the NAPRTCS centers with the most recent 150 cases to obtain additional follow‐up data not collected in the master registry, our objective being to determine the recent outcomes after PTLD and determine prognostic factors. We received 92 completed responses, in which only 12 (13%) deaths were reported, 2 from nonmedical causes, 10 with a functioning graft. Kaplan–Meier‐calculated patient survival was 90.6% at 1 year and 87.4% at 3, 4 and 5 years post‐PTLD. Graft survival post‐PTLD was 81.8% at 1 year, 68.0% at 3 years and 65.0% at 5 years. Seven patients received a retransplant after PTLD, with no PTLD recurrence reported. Using all 235 PTLD cases, the covariates associated with better patient survival were more recent year of PTLD diagnosis (adjusted hazard ratio AHR 0.86, p < 0.001), and with worse survival were late PTLD (AHR 1.98, p = 0.0176) and patient age above 13 at PTLD (AHR 3.43, p value 0.022). In children with kidney transplants, patient survival has improved with more recent PTLDs.     

Post‐transplant lymphoproliferative disorder after pancreas transplantation: a United Network for Organ Sharing database analysis

There are not a great deal of data on post‐transplant lymphoproliferative disorder (PTLD) following pancreas transplantation. We analyzed the United Network for Organ Sharing national database of pancreas transplants to identify predictors of PTLD development. A univariate Cox model was generated for each potential predictor, and those at least marginally associated (p < 0.15) with PTLD were entered into a multivariable Cox model. PTLD developed in 43 patients (1.0%) of 4205 pancreas transplants. Mean follow‐up time was 4.9 ± 2.2 yr. In the multivariable Cox model, recipient EBV seronegativity (HR 5.52, 95% CI: 2.99–10.19, p < 0.001), not having tacrolimus in the immunosuppressive regimen (HR 6.02, 95% CI: 2.74–13.19, p < 0.001), recipient age (HR 0.96, 95% CI: 0.92–0.99, p = 0.02), non‐white ethnicity (HR 0.11, 95% CI: 0.02–0.84, p = 0.03), and HLA mismatching (HR 0.80, 95% CI: 0.67–0.97, p = 0.02) were significantly associated with the development of PTLD. Patient survival was significantly decreased in patients with PTLD, with a one‐, three‐, and five‐yr survival of 91%, 76%, and 70%, compared with 97%, 93%, and 88% in patients without PTLD (p < 0.001). PTLD is an uncommon but potentially lethal complication following pancreas transplantation. Patients with the risk factors identified should be monitored closely for the development of PTLD.     

Post‐transplant lymphoproliferative disorders with naso‐ and oropharyngeal manifestation

The nasopharyngeal/oropharyngeal lymphatic tissues represent the anatomical site of Epstein–Barr virus (EBV) entry. Post‐transplant lymphoproliferative disorders (PTLD) are often associated with EBV, but little is known about the characteristics of nasopharyngeal/oropharyngeal mass‐forming PTLD. Retrospective evaluation of our own PTLD database (n = 79) and the PubMed^® database (n = 61) has been performed. Sinonasal/oro‐/nasopharyngeal lymphatic masses were early lesions (n = 54/140, 38.5%), polymorphic PTLD (n = 32/140, 23%), monomorphic B‐PTLD (n = 47/140, 33.5%) and T‐PTLD (n = 7/140, 5%). One‐fourth of lesions manifested as masses in the Waldeyer's ring, and in two‐thirds of cases, swelling of tonsils was related to manifestation of benign early lesions. Tonsil infiltration by polymorphic PTLD and monomorphic PTLD was present in one‐third of cases. Extratonsillar masses were mainly monomorphic PTLD. Meta‐analysis of our data in combination with previously published data revealed that lung transplantation and young patients are at a higher risk for earlier manifestation of monomorphic PTLD. Therapy is similar to PTLD therapy strategies, in general reduced immunosuppression and chemotherapy for polymorphic and monomorphic PTLD, and diagnostic and therapeutic surgical gross tumour resection of tonsillar/adenoid lesions. In summary, it is relevant for the clinical differential diagnosis that oro‐/nasopharyngeal aggressive PTLD manifested in ~30% as tonsillar masses and >90% at extratonsillar sites.     

Clinical characteristics and outcomes of PTLD following intestinal transplantation

Post‐transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single‐center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy‐proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow‐up time of 6.4 (1.6‐14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re‐ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.     

Herpes zoster in kidney transplant recipients: protective effect of anti‐cytomegalovirus prophylaxis and natural killer cell count. A single‐center cohort study

Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post‐transplant year) and late HZ (years 1–5) were separately assessed. We observed 35 episodes of post‐transplant HZ after a median follow‐up of 48.3 months (incidence rate: 0.057 per 1000 transplant‐days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti‐cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01–1.13; P‐value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10‐cells/μl increase): 0.94; 95% CI: 0.88–1.00; P‐value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti‐CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post‐transplant HZ.     

Impact of antiviral prophylaxis in adults Epstein–Barr Virus‐seronegative kidney recipients on early and late post‐transplantation lymphoproliferative disorder onset: a retrospective cohort study

Post‐transplantation lymphoproliferative disorder (PTLD ) pathogenesis is related to EBV infection. Mismatch with the donor (EBV D+/R?) is the main risk factor for both early PTLD (<1 year post‐transplantation) and late (>1 year). In these at‐risk patients, the role of antiviral prophylaxis for preventing PTLD remains controversial. We analyzed the impact of antiviral drugs given to prevent CMV disease in a monocentric retrospective cohort of 73 adult kidney or kidney–pancreas EBV ‐seronegative recipients, transplanted between 01/01/2000 and 01/01/2016. Thirty‐seven (50.7%, prophylaxis group) received (val‐)aciclovir or (val‐)ganciclovir for 3–6 months and 36 (49.3%, no‐prophylaxis group) received no‐prophylaxis. Mean follow‐up was 69 ± 7.2 months in the prophylaxis group and 91 ± 10.3 months in the no‐prophylaxis group. Monitoring of EBV PCR revealed that prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99). Concerning late events, EBV ‐related neoplasia incidence was significantly lower in treated patients among whom no cases were observed, while in the no‐prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of evidence our study suggests that antiviral prophylaxis could prevent late onset PTLD .     

CNI withdrawal for post‐transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality

Post‐transplantation lymphoproliferative disorders (PTLD) are associated with poor patient and graft survival. The risk of rejection and subsequent graft loss are increased by the reduction of immunosuppression therapy, the cornerstone of PTLD treatment. This multicentre, retrospective, nonrandomized cohort study includes 104 adults who developed PTLD after renal or simultaneous renal/pancreatic transplantation between 1990 and 2007. It examines the effect of calcineurin inhibitor (CNI) withdrawal on long‐term graft and patient survival. At 10 years postonset of PTLD, the Kaplan–Meier graft loss rate was 43.9% and graft loss or death with functioning graft was 64.4%. Cox multivariate analysis determined risk factors of graft loss as PTLD stage greater than I‐II and CNI withdrawal, and for graft loss and mortality, these remained risk factors along with age over 60 years. Type and location of PTLD, year of diagnosis, and chemotherapy regime were not independent risk factors. Multivariate analysis determined CNI withdrawal as the most important risk factor for graft loss (HR = 3.07, CI 95%: 1.04–9.09; P = 0.04) and death (HR: 4.00, CI 95%: 1.77–9.04; P < 0.001). While long‐term stable renal function after definitive CNI withdrawal for PTLD has been reported, this review determined that withdrawal is associated with reduced graft and patient survival.     

Systematic review and meta‐analysis of post‐transplant lymphoproliferative disorder in lung transplant recipients

A systematic review of papers in English on post‐transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random‐effects model, and heterogeneity among studies was quantitated using I² values. Fourteen studies published from 2005 to 2015 were included in the meta‐analysis. One hundred and sixty‐four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67‐fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98‐29.70; P = .003). pOR of death for early onset PTLD (<1 year post‐LT) vs late onset (> 1 year post‐LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20‐1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI ?0.48‐0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08‐2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31‐3.52, P = .94). This meta‐analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.     

Outcomes of kidney retransplantation in recipients with prior post‐transplant lymphoproliferative disorder

Post‐transplant lymphoproliferative disease (PTLD) is an uncommon but serious complication of solid organ transplantation. Reduction in immunosuppression is the mainstay of PTLD treatment, but it may precipitate graft loss. Retransplantation remains controversial, as immunosuppression resumption may trigger PTLD relapse. Herein, we describe the experience of eight patients who underwent kidney retransplantation after successful PTLD treatment. Epstein–Barr virus (EBV) serology was not known before the first transplantation. PTLD was diagnosed 62.5 months (range 5–323 months) after transplantation and was confined to the renal allograft (n = 1), lymph nodes (n = 2), gastrointestinal tract (n = 4), or central nervous system (n = 1). Immunosuppression tapering (8/8), chemotherapy (6/8), oral cavity lymphoma excision (1/8), and allograft nephrectomy (1/8) led to hematological remission in all patients. Retransplantation was performed at a median of 55.5 months (range 29–95   months) after PTLD diagnosis. After a median follow‐up of 62.5 months (range 2–125 months) allograft survival was 87.5% (seven functioning grafts, one failed graft from chronic rejection), with no recurrence of PTLD. In all, five patients remain alive; the other three died from causes other than PTLD. In conclusion, kidney retransplantation appears to be safe in patients with prior PTLD and without major risk of hematological recurrence provided that PTLD has remitted.     

Epstein‐Barr virus load in whole blood is associated with immunosuppression,but not with post‐transplant lymphoproliferative disease in stable adult heart transplant patients

Development of Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real‐time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty‐seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1–16.9) years post‐HTX]. In follow‐up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 ± 70.2 vs. 119.6 ± 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.     

Long‐term outcome following liver transplantation for paracetamol overdose

Paracetamol overdose (POD) is a major cause of acute liver failure (ALF) requiring liver transplantation in the United Kingdom. To characterize the early and late outcome after orthotopic liver transplantation (OLT) for POD in the Scottish Liver Transplant Unit over a 14‐year period (1992–2006). Data were obtained from a prospective database combined with case‐note review. Of 127 liver transplants performed for ALF, 44 were for POD. The median age was 30 (range 18–51). In 18 patients (63.7%), POD was associated with alcohol/other drugs, nine (20.5%) had a staggered overdose and four patients (9.1%) accidentally overdosed. Nineteen patients (43.2%) had a history of previous overdose/psychiatric illness. Post‐transplant mortality during the index admission was 30% (13 patients), whilst five patients died during follow‐up. The actuarial 5‐year patient survival was 54.5%, whilst graft survival was 49.5%. Some 23% of the patients were re‐transplanted: primary nonfunction (1), hepatic artery thrombosis (3) and chronic rejection (2). Three patients had a subsequent transplant; three patients had two further transplants. Nine patients (35%) continue to have social/psychiatric issues. OLT for POD is associated with significant early and late morbidity and mortality. A multidisciplinary approach is required to identify the suitable candidates, in whom transplantation should be pursued promptly.     

Positron emission tomography scanning in the setting of post‐transplant lymphoproliferative disorders

Abstract: Background: Post‐transplant lymphoproliferative disorder (PTLD) is a serious complication of transplantation. We examined the role of positron emission tomography (PET) scanning in PTLD. Methods: All patients treated for PTLD from 2001–2006 who also underwent PET scans were reviewed. Results: Nineteen PTLD patients were included. Seventeen patients had PET scans for staging at diagnosis. Of these, two patients with primary central nervous system lymphoma and one patient with only bone marrow involvement after complete surgical resection of a bowel lesion had no abnormalities on CT or PET scan. The remaining patients had measurable, extracranial disease by CT scan and PET scan. The median maximum standard uptake value was 8.2 (range 3–30). Thirteen patients had a PET scan following treatment. Eleven of 13 patients had a complete response (CR). Two of 13 patients had persistent disease following therapy; in one of these patients, relapsed disease was documented by PET scan alone. Of the 11 patients with CR, three patients relapsed shortly thereafter. In each case, at the time of relapse, the PET scan confirmed recurrent disease regardless of histopathologic subtype. Conclusions: PET scans may have a role in the staging and follow‐up of patients with PTLD. Additional prospective studies are warranted.     

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Post‐transplant lymphoproliferative disorder (PTLD) may compromise long‐term outcome of lung transplant (LTx) recipients. A case‐control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post‐transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166‐1132) days; and 54.8% had early‐onset PTLD versus 45.2% late‐onset PTLD. At LTx, more Epstein‐Barr virus (EBV)‐seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C‐reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5‐year survival post‐LTx (66.6% versus 91.5%), resulting in worse CLAD‐free survival (HR 2.127, 95%CI 1.006‐4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473‐7.382; P=.0037) compared to Controls. Late‐onset PTLD had worse survival compared to early‐onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long‐term outcome post‐LTx.     

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario,Canada

In the United States, kidney transplant rates vary significantly across end‐stage renal disease (ESRD) networks. We conducted a population‐based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1‐, 5‐, and 10‐year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for “healthy” dialysis patients (aged 18–50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow‐up of 11 years). Among 23 022 chronic dialysis patients, the 10‐year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8–10.7%) to 31.4% (95% CI 16.5–47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2–0.5) to 1.5 (95% CI 1.4–1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.     

Pre‐transplant dialysis modality does not influence short‐ or long‐term outcome in kidney transplant recipients: analysis of paired kidneys from the same deceased donor

Previous studies have reported contradictory results regarding the effect of pre‐transplant dialysis modality on the outcomes after kidney transplantation (KT). To minimize the confounding effect of donor‐related variables, we performed a donor‐matched retrospective comparison of 160 patients that received only one modality of pre‐transplant dialysis (peritoneal dialysis [PD] and hemodialysis [HD] in 80 patients each) and that subsequently underwent KT at our center between January 1990 and December 2007. Cox regression models were used to evaluate the association between pre‐transplant dialysis modality and primary study outcomes (death‐censored graft survival and patient survival). To control for imbalances in recipient‐related baseline characteristics, we performed additional adjustments for the propensity score (PS) for receiving pre‐transplant PD (versus HD). There were no significant differences according to pre‐transplant dialysis modality in death‐censored graft survival (PS‐adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [95% CI]: 0.25–1.68) or patient survival (aHR: 0.58; 95% CI: 0.13–2.68). There were no differences in 10‐year graft function or in the incidence of post‐transplant complications either, except for a higher risk of lymphocele in patients undergoing PD (odds ratio: 4.31; 95% CI: 1.15–16.21). In conclusion, pre‐transplant dialysis modality in KT recipients does not impact short‐ or long‐term graft outcomes or patient survival.     

Long‐term patient survival and kidney allograft survival in post‐transplant diabetes mellitus: a single‐center retrospective study

A decade ago, observations suggested that post‐transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and changes in the immunosuppressive regimen may have modified this association. Single‐center analysis of 1990 (age>18; transplantation date 1996–2012) primary kidney recipients (KTR). Patients with <12 months follow‐up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post‐transplant year not treated with glucose‐lowering medications (GLM) at 12 months, PTDM in the first post‐transplant year treated with GLM at 12 months, and pretransplant diabetes. Cox proportional hazards models were used to examine the relationship of PTDM with allograft and patient survival. Mean follow‐up time was 6.8 years for allograft survival and 7.4 years for patient survival. PTDM treated with medication at year one was not associated with allograft survival (HR 1.28, 95% CI 0.97–1.69), but was significantly associated with overall mortality and death with functioning graft (DWFG) (HR overall: 1.81, 95% CI 1.36–2.39; HR DWFG: 1.59 95% CI 1.05–2.38). In this cohort, KTR with PTDM being treated with glucose‐lowering medication at 12 months experienced significantly shorter overall survival and survival with functioning graft.     

Lymphoma after living donor kidney transplantation: an Iranian multicenter experience

Introduction  Post-transplant lymphoproliferative disorders (PTLD) are well-recognized complications in solid organ recipients. Limited data exist about the development of PTLDs in living kidney recipients. This study deals with a multicenter nationwide experience with kidney recipients from living donors. Methods  We reviewed data of PTLD patients from a total population of 6,500 patients transplanted at three different transplant centers in Iran from 1984 to 2006. We also compared their data with 2,250 normal kidney recipients of Baqiyatallah Transplant Center. Data were analyzed to determine potential correlates with the occurrence of PTLD and patient outcome. Results  Overall, 31 patients were diagnosed as having post-transplant lymphomas. The incidence of PTLD in our kidney transplant population comprised 0.47%. Sixteen (53%) PTLD patients were females, whereas 15 (47%) were males. The mean ages at transplantation and diagnosis were 37.1 and 41.9, respectively. Twelve (63%) patients died, and seven are alive. All deaths occurred within the 1st year after PTLD diagnosis. The mean time period from transplantation to diagnosis of PTLD was 64 (0.7–173) months. Localization of PTLD in the brain associated the worst outcome. Compared to non-PTLD patients, PTLD patients were significantly female predominated (51.6% vs. 32.2%; P = 0.03) and had lower age at transplantation (36.9 years vs. 42.9 years, respectively; P = 0.01). Patients under immunosuppressive regimens containing azathioprine were at higher risk for acquiring PTLDs compared to those with a MMF-containing regimen. Conclusion  PTLD is a major threat to kidney transplant recipients. Immunosuppressive agents have a significant role in developing the disease. Early detection of the disease and using more safe immunosuppresants may have beneficial effects on patient outcomes and incidence of the disease.     

Low‐Dose Chemotherapy and Rituximab for Posttransplant Lymphoproliferative Disease (PTLD): A Children's Oncology Group Report

Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains problematic. A phase II trial adding rituximab to a low‐dose cyclophosphamide and prednisone regimen was conducted for pediatric patients with Epstein–Barr virus (EBV) (+), CD20 (+) PTLD. Fifty‐five patients were enrolled. Toxicity was similar for cycles of therapy containing rituximab versus those without. The complete remission (CR) rate was 69% (95% confidence interval (CI); 57%–84%). Of 12 patients with radiographic evidence of persistent disease at the end of therapy, eight were in CR 28 weeks later without further PTLD therapy. There were 10 deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2‐year event‐free survival (alive with functioning original allograft and no PTLD) was 71% (95% CI: 57%–82%) and overall survival was 83% (95% CI: 69%–91%) with median follow‐up of 4.8 years. Due to small numbers, we were unable to determine significance of tumor histology, stage of disease, allograft type or early response to treatment on outcome. These data suggest rituximab combined with low‐dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD following solid‐organ transplantation.     

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low‐Dose Valganciclovir Prophylaxis

Late‐onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R–) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6‐month low‐dose valganciclovir (VGCV) prophylaxis, risk factors for late‐onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R– kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow‐up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late‐onset CMV disease (AHR 2.91, 95% CI 1.18–7.20, p = 0.021 and AHR 1.03, 95% CI 1.01–1.06, p = 0.016, respectively). Late‐onset CMV disease was associated with increased risk for death‐uncensored graft loss (AHR 2.95, 95% CI 1.15–7.61, p = 0.025). In conclusion, late‐onset CMV disease continues to negatively impact kidney transplant outcome despite 6‐month low‐dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.