Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

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 disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

The Impact of EBV Status on Characteristics and Outcomes of Posttransplantation Lymphoproliferative Disorder

We examined the associations of Epstein–Barr virus (EBV) status with characteristics and outcomes of posttransplantation lymphoproliferative disorder (PTLD) by studying 176 adult solid organ transplant recipients diagnosed with PTLD between 1990 and 2013 (58 [33%] EBV‐negative; 118 [67%] EBV‐positive). The proportion of EBV‐negative cases increased over time from 10% (1990–1995) to 48% (2008–2013) (p < 0.001). EBV‐negative PTLD had distinct characteristics (monomorphic histology, longer latency) though high‐risk features (advanced stage, older age, high lactate dehydrogenase, central nervous system involvement) were not more common compared to EBV‐positive PTLD. In multivariable analysis, EBV negativity was not significantly associated with worse response to initial therapy (adjusted odds ratio, 0.84; p = 0.75). The likelihood of achieving a complete remission (CR) was not significantly different for EBV‐negative versus EBV‐positive PTLD including when therapy was reduction of immunosuppression alone (35% vs. 43%, respectively, p = 0.60) or rituximab (43% vs. 47%, p = 1.0). EBV negativity was also not associated with worse overall survival (adjusted hazard ratio, 0.91; p = 0.71). Our findings indicate that EBV status is not prognostic or predictive of treatment response in adults with PTLD. The high proportion of EBV‐negative disease diagnosed in recent years highlights the need for new strategies for prevention and management of EBV‐negative PTLD.     

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk – an observational,retrospective study

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV‐LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS‐CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR < 60 ml/min) in 26.5%. CS‐CMV reactivation occurred in 25% of patients. Twenty‐six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre‐LT DM [HR = 4.6 95% CI (1.6, 13), P = 0.004] and CS‐CMV [HR = 4.7 95% CI (1.8, 12.5), P = 0.002]. CS‐CMV was not independently associated with the remaining endpoints except for survival (P = 0.03). In our series, CS‐CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.     

Comparative analysis of post‐transplant lymphoproliferative disorder after kidney transplantation versus hematopoietic stem cell transplantation

Post‐transplant lymphoproliferative disorder (PTLD) is a major complication caused by immune‐suppression after transplantation. Survival outcome is known to be poor and the characteristics are not fully understood because of its rare incidence. This single center retrospective study enrolled 41 adult PTLD patients after kidney‐transplantation (KT, n = 28) and hematopoietic stem cell transplantation (HSCT, n = 13) from 1992 to 2012. We compared the characteristics and estimated the survival outcomes according to several factors [age‐adjusted‐IPI (aaIPI), pathologic subtype, viral status, extranodal manifestation] and added some significant parameters to aaIPI scoring system. Post‐HSCT‐PTLD patients were younger and showed earlier onset, and viral status was more frequently identified. Ten‐year OS of the entire group was 44% but the 10‐year OS was not significantly different between post‐KT‐PTLD and post‐HSCT‐PTLD (39% vs. 56%, P = 0.860). The time onset of PTLD and viral statuses were not meaningful, however, aaIPI, age > 50, extranodal manifestation and monomorphic subtype were predictive for OS. We used those factors for PTLD‐specific scoring which showed intermediate‐risk (HR = 7.1, P = 0.019) and high‐risk (HR = 16.5, P = 0.001) presented worse OS compared to low‐risk subgroup. Although the treatment strategies were heterogenous, this study showed comprehensive PTLD data between KT versus HSCT, and our PTLD‐specific scoring might be validated by another larger studies.     

Human herpesvirus‐6 encephalopathy after hematopoietic stem cell transplantation and class I human leukocyte antigen

Human herpesvirus‐6 (HHV‐6) encephalopathy is a serious complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although reactivation of HHV‐6 is often observed after allo‐HSCT, encephalopathy only affects a few patients with HHV‐6 reactivation. Human leukocyte antigen (HLA) class I is expressed by most somatic cells, and a relationship between some class I alleles and neurological diseases has been reported. The HHV‐6 load at two, three, and four weeks after allo‐HSCT was examined. HHV‐6 encephalopathy was diagnosed from symptoms, results of cerebrospinal fluid examination, and magnetic resonance imaging findings. The relation between HHV‐6 reactivation or encephalopathy and the HLA class I status of the recipients was investigated. In 130 patients, 147 allo‐HSCT transplantation procedures were carried out. HHV‐6 reactivation and encephalopathy occurred in 56 and nine procedures, respectively. HLA mismatch (p = 0.008) and unrelated donor (p = 0.001) were associated with HHV‐6 reactivation, but not with HHV‐6 encephalopathy. HHV‐6 encephalopathy was more frequent in patients with HLA‐B*40:06 (p = 0.027). In addition, HLA‐A*26:01 and HLA‐B*40:06 were found to be associated with each other (p = 0.089), while HLA‐B*40:06 and HLA‐C*08:01 showed a significant association (p < 0.001). The HLA class I alleles of recipients may be associated with the occurrence of HHV‐6 encephalopathy after allo‐HSCT.     

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.     

Pre‐existing anti‐HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT

Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti‐HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti‐HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti‐HLA antibodies. Pre‐existing anti‐HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti‐HLA class I antibodies. Anti‐HLA antibodies were associated with worse five‐yr survival (78.6% vs. 100%, p = 0.021) and higher treatment‐related mortality (21.4% vs. 0%, p = 0.028) compared with antibody‐negative patients. Anti‐HLA class I antibody‐positive patients had poorer five‐yr survival (75.0%) than anti‐HLA class I&II antibody‐positive and antibody‐negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti‐HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post‐HSCT mortality. Pre‐existing anti‐HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti‐HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT.     

Monitoring Infection with Epstein–Barr Virus among Seromismatch Adult Renal Transplant Recipients

Patients who undergo Epstein–Barr virus (EBV) seromismatch (D+/R − ) transplants have a higher risk for the development of post‐transplant lymphoproliferative disorder (PTLD). Adult renal transplant recipients at a single institution were prospectively monitored for EBV during the first year post‐transplant. Over a 2‐year period, 34 patients (7.78%) were identified as being EBV D+/R − recipients. Patients who developed symptoms or had persistent viremia were pre‐emptively administered rituximab. Six recipients were discharged without monitoring on the protocol. Of those six, three (50%) developed PTLD and all three lost their grafts. Twenty (60.6%) of the 34 recipients developed viremia during the first year post‐transplant. Of the recipients who became viremic, six (30%) received rituximab. None of the six who received rituximab‐developed PTLD. We found that recipients who were not monitored on the protocol were more likely to have PTLD and graft loss compared to those who were (p = 0.008). Post‐transplant monitoring of adults who undergo EBV D+/R − kidney transplants for viremia and symptoms associated with EBV infection may prompt intervention which reduces the incidence of PTLD within the first year. Use of rituximab in preventing PTLD among patients with primary EBV infection requires further prospective study to determine its overall safety and efficacy.     

Transplantation of solid organ recipients shedding Epstein‐Barr virus DNA pre‐transplant: A prospective study

Epstein‐Barr virus (EBV) poses a significant threat to patient and graft survival post‐transplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease post‐transplant. To test this hypothesis, we conducted a 5‐year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pre‐transplant samples were available from 98 subjects. EBV DNA was detected pre‐transplant in 32 of 95 (34%) and 5 of 93 subjects (5%) in oral wash and blood, respectively. Recipients with and without detectable pre‐transplant EBV DNA were not significantly different demographically and had no significant difference in patient and graft survival (P = .6 for both comparisons) or post‐transplant EBV viremia‐free survival (P = .8). There were no cases of EBV‐related disease or post‐transplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pre‐transplant. In conclusion, detectable EBV DNA pre‐transplant was not associated with differences in patient/graft survival, post‐transplant EBV viremia, or EBV‐related diseases including PTLD.     

Risk factors for post‐transplant lymphoproliferative disorder after Thymoglobulin‐conditioned hematopoietic cell transplantation

Epstein‐Barr virus (EBV)‐induced post‐transplant lymphoproliferative disorder (PTLD) occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG‐conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy‐diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, P = .43) and similar overall survival (63% vs 67% at 2 years, P = .23) even though there was a trend toward higher PTLD incidence with the prompt therapy. Donor positive with recipient negative EBV (D+R?) serostatus was a risk factor for developing PTLD. Older patient age, HLA‐mismatched donor, and graft‐versus‐host disease were not associated with increased risk of PTLD. In summary, in ATG‐conditioned HCT, D+R? serostatus, but not older age, mismatched donor or GVHD is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival.     

Characteristics,risks, and outcomes of post‐transplant lymphoproliferative disease >3 years after pediatric heart transplant: A multicenter analysis

Post‐transplant lymphoproliferative disorder (PTLD) is a significant complication after pediatric heart transplantation (HT), occurring in 5%‐15% of patients within 3 years. Data >3 years from HT are limited. We sought to describe the prevalence, risk factors, and outcomes of PTLD occurring late (>3 years) after pediatric HT in the Pediatric Heart Transplant Study from 1993 to 2010. Among 3844 primary HT patients, 110 (3%) developed late, nonrecurrent PTLD. The hazard rate for late PTLD was constant at 0.01 events/year out to 20 years after HT. Risk factors for late PTLD were younger age at HT (HR 1.06, P = 0.003) and Epstein‐Barr virus (EBV) naivety (HR 1.65, P = 0.02). Survival after late PTLD was 86% and 68% at 1 and 5 years, with nonwhite race (HR 2.27, P = 0.03) and earlier year of HT (HR 1.03, P = 0.04) independently associated with mortality. Acute rejection and infection were both common after late PTLD, occurring in 26% and 34% of patients. The constant late hazard and contribution of EBV to late PTLD suggest that vigilance for development of PTLD, including for EBV conversion, should persist indefinitely after pediatric HT. The reasons for elevated risk of death for nonwhites after late PTLD are unclear and warrant further investigation.     

Correlations with six‐month protocol biopsy findings in pediatric transplant recipients on low‐ and regular‐dose CNI regimens

Protocol biopsies (PB) are seldom performed after pediatric kidney transplantation (KTx), and factors influencing PB results have not previously been investigated. We performed PB in 79 children six months after KTx and evaluated the results using Banff 2007 criteria. Complications such as bleeding or infections were not detected. The influence of different variables on PB results was evaluated by covariance analysis. Children treated with a low‐dose calcineurin inhibitor (CNI) together with an mTOR inhibitor exhibited decreased subclinical rejection (0% vs. 19%, p = 0.001) and decreased interstitial fibrosis and tubular atrophy (IF/TA) (15% vs. 42%, p = 0.013) compared with patients treated with a conventional regimen consisting of normal‐dose CNI and mycophenolate mofetil. Children with IF/TA had a lower GFR four wk after Tx (83 ± 22 vs. 62 ± 20 mL/min/1.73 m², p = 0.001). Cold ischemia time, living‐related donors, pre‐emptive KTx, and donor age did not influence PB results. Treatment with low‐dose CNI and mTOR inhibitor and high GFR directly after Tx are the main factors associated with less inflammation and fibrosis in PB and might therefore lead to better long‐term graft function.     

Characteristics of Epstein–Barr viraemia in adult liver transplant patients: A retrospective cohort study

Therapeutic immunosuppression following solid organ transplantation increases the risk of Epstein–Barr (EBV) viraemia, which is implicated in post‐transplant lymphoproliferative disease (PTLD). We retrospectively analysed the incidence of EBV viraemia and clinical outcomes in 98 liver transplant recipients. Patients underwent EBV DNA monitoring by whole‐blood PCR: EBV levels were correlated with clinical parameters and outcomes for a median of 249 days. 67% patients developed EBV viraemia (EBV DNA ≥100 copies/ml) and 30% had sustained viraemia. There was a trend towards higher hazard ratios for viraemia with exposure to aciclovir (HR 1.57, P = 0.12) or in recipients of a poorly HLA‐matched graft (HR 1.62, P = 0.10). These associations became significant in the subgroup with >90 days surveillance; HR 2.54 (P = 0.0015) for aciclovir and HR 1.99 (P = 0.03) for poorly matched grafts. The converse was true with ganciclovir (HR 0.56 P = 0.13). Viraemia was more prolonged in men (median duration 7 days vs 1; P = 0.01) and in those with lower UKELD scores (11 days vs 1 day; P = 0.001) but shortened with ganciclovir exposure (P = 0.06). Younger patients were more likely to have high peak viral loads (P = 0.07). No clinical signs or symptoms or adverse outcomes were associated with EBV reactivation.     

Low‐dose methotrexate may preserve a stronger antileukemic effect than that of cyclosporine after modified donor lymphocyte infusion in unmanipulated haploidentical HSCT

To compare the impacts of low‐dose methotrexate (MTX) with cyclosporine (CSA) on graft‐versus‐host disease (GVHD) and graft‐versus‐leukemia (GVL) effect after haploidentical modified donor lymphocyte infusion (DLI). Fifty‐five consecutive patients who had relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) and received modified DLI were retrospectively studied. Forty‐one patients received CSA and 14 received low‐dose MTX after DLI to prevent DLI‐associated GVHD. The incidence of acute GVHD and grade 2–4 acute GVHD in MTX group showed a trend toward being higher than in CSA group (61.0% vs. 37.3%, p = 0.198 and 61.0% vs. 35.5%, p = 0.155). However, no significant difference in the incidence of grade 3–4 acute GVHD between two groups (p = 0.982) was observed. Moreover, compared with CSA, patients treated with MTX had lower re‐relapse rate (38.1% vs. 80.8%, p = 0.029), better disease‐free survival (DFS) (51.9% vs. 15.6%, p = 0.06), and higher absolute lymphocyte counts at 30, 45, 60, and 90 d after modified DLI (p < 0.05). This study suggested that after haploidentical modified DLI, low‐dose MTX is at least as effective as CSA in the prevention of DLI‐associated GVHD and probably allowed stronger GVL effect than CSA. This phenomenon was probably due to a direct antitumor effect and a better reconstitution of lymphocytes after modified DLI induced by low‐dose MTX.     

Epileptic seizures in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence,risk factors,and survival rates

The incidence of epileptic seizures among allogeneic hematopoietic stem cell transplant (allo‐HSCT) patients has been poorly described. No report has systematically studied epilepsy's possible causes, risk factors, and effect on prognosis among allo‐HSCT patients. We retrospectively examined data from 1461 patients who underwent allo‐HSCT within the past 6.5 yr at the Institute of Hematology and People's Hospital, Peking University. The cumulative incidence of all epileptic seizure complications was 7.1%. Of the 79 transplant patients who had epileptic seizures, 3 (3.8%) experienced a seizure during the conditioning stage, 52 (65.8%) between day 0 and day 100, 20 (25.3%) from day 100 to the first year, and 4 (5.1%) after the first year. Multivariate regression analysis identified the age of the recipient as (≤18 yr) (p < 0.001), donor type (p = 0.004), graft versus host disease (aGVHD) (p = 0.018), and hyponatremia (p = 0.003) as independent risk factors for epileptic seizures among allo‐HSCT patients. The median survival time of patients with epileptic seizures was 246 d after transplantation (ranging between 18 and 2170 d). Survival after one yr and 6.5 yr was significantly reduced in patients who developed epileptic seizure complications compared with those who did not (57.2% vs. 75.7% at one yr, p = 0.015, and 31.1% vs. 71.4% at five yr, p < 0.001). Of the 79 patients who experienced epileptic seizure complications, 53.2% died (n = 42). The survival rate of these patients was relatively low, and cerebrovascular disorders or central nervous system infection‐related epileptic seizures usually resulted in a high mortality and poor prognosis. A patient transplantation age which is younger than 18 yr, related mismatched transplants, aGVHD, and hyponatremia are risk factors for epileptic seizures in allo‐HSCT recipients. Epileptic seizures among allo‐HSCT patients are associated with a poor prognosis.     

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.     

Pre‐existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation

The aim of this study was to examine the impact of pre‐existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post‐transplant variables. Five‐yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre‐existing DM. Sequential Cox regression models demonstrated that pre‐existing DM was consistently associated with a higher risk of death (HR 2.3–3.0, p < 0.01) and graft failure (HR 1.5–1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre‐existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.     

The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation

Donor lymphocyte infusion (DLI) is often used to enhance the graft‐versus‐leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). In this study, we first evaluated the impact of the cell composition of a modified DLI (mDLI) on the prognoses of patients. A total of 194 patients undergoing allo‐HSCT were enrolled and received mDLI for various clinical reasons. The infused cellular components of the mDLI were examined by flow cytometry. The results showed that infusion with a lower dose of CD14⁺ cells (<0.33 × 10⁸/kg) was an independent risk factor for the occurrence of II–IV acute graft‐versus‐host disease (aGVHD) (HR = 0.104, p = 0.032) in human leukoctye antigen‐identical transplant patients. In addition, a dose of CD14⁺ cells greater than the 50th percentile was associated with a lower incidence of hematological relapse and longer disease‐free survival (DFS) after the mDLI (relapse: HR = 0.193, p = 0.007; DFS: HR = 0.259, p = 0.016). However, we also found that a greater number of CD14⁺ cells were an independent risk factor for II–IV aGVHD (HR = 1.758, p = 0.034) in haploidentical allo‐HSCT. In conclusion, our data were the first to demonstrate that the cell composition of a 56 mDLI played a distinct role in different types of allo‐HSCT. This finding provided a novel approach for the development of cellular therapies by manipulating the components of infused cells.