Outcome Of Post-transplant Lymphoproliferative Disorders Research Articles

#99 Clinical characteristics and outcomes of PTLD after kidney transplant: a single center experience

Abstract Background and Aims Post-Transplant Lymphoproliferative Disorder (PTLD) is a serious and potentially fatal complication of immunosuppression in kidney transplantation. Given the rarity of this entity, a high index of suspicion is necessary. We aimed to review the incidence, clinical presentation, histological subtypes, treatment, patient and graft survival of PTLD in kidney transplant patients in our unit. Methods Observational retrospective study, including adults diagnosed with PTLD between 1998 and 2023 in a Kidney Transplantation Center. Results Of 1390 kidney transplant recipients, 4 (0.3%) developed PTLD with a mean age of 52 ± 12.5 years. All cases were late-onset, occurring one year after transplantation with a median time from transplantation to diagnosis of 16.7 ± 7.3 years (range: 5-22 years). Of these, none had EBV donor/recipient mismatch. Two patients had prior rejection episodes (one patient, acute T cell-mediated rejection and the other patient, acute T cell-mediated rejection and active antibody mediated rejection). Clinical presentation was variable. Non-specific constitutional symptoms such as fever, fatigue and night sweats were present in all patients. Organ-specific symptoms were also present: lumbar pain in one patient with bone involvement, and delirium and lethargy in two patients with central nervous system involvement. Laboratory analyses revealed an increase in serum LDH in all patients. The primary sites of involvement were central nervous system (50%), lymph nodes (25%) and bone (25%). At PTLD diagnosis, immunosuppression included: tacrolimus (100%), mycophenolate mofetil (75%), low-dose of steroids (50%) and everolimus (25%). Regarding histologic classification, 75% were monomorphic and 25% polymorphic. In the monomorphic group, all patients had Diffuse Large B Cell Lymphoma (CD20 positive). In the polymorphic group, the patient had a Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative). Immunosuppression therapy was reduced in all patients with discontinuation of mycophenolate mofetil and tacrolimus. In the patient who was taking everolimus, the dose was increased due to the potential clinical antitumor effects of mTOR inhibition. Additional therapies included, rituximab in monotherapy or in combination with chemotherapy (R-CHOP) in the monomorphic group. Palliative measures were selected for one patient of this group due to advanced disease. The patient with Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative) did chemotherapy with ABVD. None of the patients underwent surgery or radiation therapy. Two patients needed dialysis. Three patients died in the first four weeks after PTLD diagnosis, all due to infectious complications. Patient survival was 25% one year after diagnosis. Conclusions Although the incidence of PTLD was low following kidney transplantation, its impact was significant in kidney graft and overall patient survival. Given the poor prognosis, new therapies combining high efficacy and low toxicity are an urgent unmet medical need in this field.

Characterization and outcome of post-transplant lymphoproliferative disorders within a collaborative study.

Post-transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that can arise after solid organ transplantation (SOT) and allogeneic hematopoietic transplantation (allo-HSCT). In this multi-center retrospective study, we compare patient characteristics, therapies, and outcomes of PTLD after allo-HSCT and SOT. Twenty-five patients (15 after allo-HSCT and 10 after SOT) were identified who developed PTLD between 2008 and 2022. Median age (57 years; range, 29-74 years) and baseline characteristics were comparable between the two groups (allo-HSCT vs SOT), but median onset of PTLD was markedly shorter after allo-HSCT (2 months vs. 99 months, P<0.001). Treatment regimens were heterogeneous, with reduction of immunosuppression in combination with rituximab being the most common first-line treatment strategy in both cohorts (allo-HSCT: 66%; SOT: 80%). The overall response rate was lower in the allo-HSCT (67%) as compared to the SOT group (100%). Consequently, the overall survival (OS) trended towards a worse outcome for the allo-HSCT group (1-year OS: 54% vs. 78%; P=0.58). We identified PTLD onset ≤150 days in the allo-HSCT (P=0.046) and ECOG >2 in the SOT group (P=0.03) as prognostic factors for lower OS. PTLD cases present heterogeneously and pose unique challenges after both types of allogeneic transplantation.

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication after transplantation. In this retrospective, monocentric study we aimed to collect real life data regarding PTLD and determine the role of Epstein Barr Virus (EBV) status and year of diagnosis on prognosis. We identified 196 biopsy-proven PTLD after solid organ transplantation (SOT) diagnosed at the University Hospitals Leuven (Belgium) from 1989 to 2019. EBV status was positive in 61% of PTLD. The median overall survival (OS) was 5.7years (95% CI: 2.99-11.1). Although EBV positivity was not significantly correlated with OS in multivariate analyses (HR: 1.44 (95% CI: 0.93-2.24); p = 0.10), subgroup analysis showed a significantly better median OS for EBV negative post-transplant diffuse large B-cell lymphoma (DLBCL) compared to EBV positive post-transplant DLBCL (8.8 versus 2.5 years respectively; p = 0.0365). There was a significant relation between year of PTLD diagnosis and OS: the more recent the PTLD diagnosis, the lower the risk for death (adjusted HR: 0.962 (95% CI: 0.931-0.933); p = 0.017). In conclusion, the prognosis of PTLD after SOT has improved in the past decades. Our analysis shows a significant relation between EBV status and OS in post-transplant DLBCL.

Abstract 12595: De Novo Lymphoproliferative Disorders in Heart Transplant Recipients: Predictors and Clinical Outcomes

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, clinical characteristics and predictors of PTLD in the real world have not been well studied. Methods We retrospectively analyzed clinical characteristics, predictors, and outcomes of PTLD, in 28,136 recipients of heart alone transplants between January 2000 and June 2015 from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. Results Ten-year incidence of PTLD after successful discharge from HTx during 2000-2007 was 3.8%. The adjusted overall risk of mortality was significantly higher in patients diagnosed with PTLD within 3 years after HTx compared to those without PTLD (HR 2.22, 95% CI 1.86-2.65, p&lt;0.001). Bimodal age peak of the PTLD incidence within the 3 years of HTx and mortality after the diagnosis of PTLD was noted. Both adjusted risk of PTLD incidence and mortality were lower in recent HTx; lower incidence and mortality in era of 2008-2015, compared to 2000-2007 (Incidence: HR 0.75, 95% CI 0.57-0.98, p=0.038) (Mortality: HR 0.86, 95% CI 0.81-0.91, p&lt;0.001). Age at transplant, male recipient, high risk Epstein-Barr virus (EBV) mismatch (donor positive and recipient negative for EBV) were independent risk factors, while primary maintenance therapy with cyclosporine (vs. tacrolimus) at initial discharge was a protective factor for PTLD within 3 years. Conclusions The incidence as well as mortality of PTLD has decreased in recent years of HTx, possibly with advances in changed pattern of immunosuppression according to patient profile. Clinical characteristics such as age, male gender, EBV status and rejection history are key factors for assessing the risk of PTLD, which can be detrimental in the course of post HTx care.

631P A meta-analysis of the outcome of post-transplant lymphoproliferative disorder in adult patients after hematopoietic stem cell transplant

Post-transplant lymphoproliferative disorder is a fatal complication that can occur early after solid organ or hematopoietic stem cell transplantation (HSCT). It represents a spectrum of Epstein Barr virus (EBV)-related clinical diseases, from benign mononucleosis like illness to malignancies like non-Hodgkin's lymphoma. Some of the established risk factors for PTLD are HLA mismatching, T-cell depletion, and the use of anti-lymphocyte antibodies as conditioning or immunosuppression for the treatment of graft-versus-host disease.

Presentation and outcomes of post-transplant lymphoproliferative disorder at a single institution pediatric transplant center.

This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation. We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016. Of 594 patients included in this study, 41(6.9%) were diagnosed with PTLD. Median age at transplant was 5.6(IQR 1.7-16.1) years. Proportion of PTLD cases by organ transplanted and median time (IQR) to disease onset were: heart 11/144(7.6%) at 13.6(8.5-55.6) months, lung 7/52(13.5%) at 9.1(4.9-35) months, kidney 8/255(3.1%) at 39.5(13.9-57.1) months, liver 12/125(9.6%) at 7.7(5.5-22) months, intestine 0/4(0%), and multi-visceral 3/14(21.4%) at 5.4(5.4-5.6) months. No significant correlation was seen between recipient EBV status at transplant and timing of development of PTLD. There were six early lesions, 15 polymorphic, 19monomorphic, and one uncharacterizable PTLD. Following immunosuppression reduction, 30 patients received rituximab, and 14 required chemotherapy. At median 25(IQR 12-53) months follow-up from the onset of PTLD, eight patients died secondary to transplant related complications, three are alive with active disease, and 30have no evidence of disease. PTLD is a significant complication following pediatric solid organ transplantation. EBV levels in conjunction with symptomatic presentation following transplant may assist in detection of PTLD. Most patients can achieve long-term disease-free survival through immunosuppression reduction, anti-CD20 treatment, and chemotherapy in refractory cases.

Survival outcomes of post-transplant lymphoproliferative disorder: A 12-year analysis.

e19543 Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of chronic immunosuppression in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients. With an overall incidence of ̃ 1 percent in the transplant recipients, it is the most common malignancy, with the exception of skin cancer, after SOT in adults. There is a paucity of information concerning the outcomes and prognostic indicators of PTLD. Methods: We queried the National Cancer Database (NCDB) from 2004 – 2015 for patients with diagnosis of PTLD. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival. Additionally, Poisson regression was used to test the association between baseline variables and days to event. All statistical analyses were performed using R 4.0.3. Results: Total number of patients identified by inclusion criteria was 425. 1-year OS was 73% (CI 0.684, 0.776), 3-year OS 63% (CI 0.581, 0.683), and 5-year OS 56% (CI 0.502, 0.619) in patients with survival data available (n = 365). 263 patients were excluded due to incomplete data, yielding a final cohort of 192 patients for correlational analysis. The median age was 59 years. Majority were males (60%), &lt; 65 year old (75.5%), Hispanics (91%), and had Charlson-Deyo Comorbidity score of 0 (63.5%). 77% were Caucasians while 15.6% were African Americans. OS was longer in males, Caucasians, patients who received radiation (versus no radiation), those treated at academic or comprehensive cancer center (versus community cancer center), had annual income &gt; $63000 (versus &lt; $63000) by Poisson regression analysis, however the difference was not statistically significant. Conclusions: Our data demonstrates a trend toward poor survival with socioeconomic and treatment variables including gender, race, annual income, treatment center expertise and radiation treatment. Randomized trials are needed to further assess the outcomes of PTLD.

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium

IntroductionRabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a “standard” higher dose.MethodsWe performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival.ResultsTwo hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07).ConclusionA low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

1091. Incidence of Post-Transplant Lymphoproliferative Disorders among Epstein-Barr Virus Donor Positive, Recipient Negative Adult Solid Organ Transplant Recipients

BackgroundEpstein-Barr virus (EBV) donor positive (D+), recipient negative (R-) serostatus is a major risk factor for post-transplant lymphoproliferative disorder (PTLD) in adult solid organ transplant recipients (SOTR). Few studies have systematically characterized absolute organ transplant type-specific incidence, timing, and outcomes of PTLD in adult EBV D+R- SOTR.MethodsWe retrospectively assessed the incidence, timing, and associated morbidity and mortality of biopsy-confirmed PTLD (WHO classification) among consecutive adult SOTR between Jan 1, 2000 and Apr 30, 2018 at a single university center, and who had a minimum 2 years of follow-up. Antibodies to EBV (viral capsid antigen and nuclear antigen) were assessed in candidates and donors by FDA-cleared ELISA assay. Donors with unknown serology were considered seropositive based on the known prevalence of >93% seropositivity in this donor population.ResultsAmong 4,923 SOTR, prior to transplant, 4,770 (96.9%) were R+ (regardless of donor status), 144 (2.9%) were D+R-, and 9 (0.2%) were D-R-. PTLD incidence by last follow-up was higher among D+R- (15/144 [10.4%]) than R+ (61/4,770 [1.2 %]), P < 0.0001, and occurred earlier after transplant (median 9.6 months [IQR 6.1-34.2] versus 35.1 months [IQR 7.1-73.1]), P= 0.003, respectively. Among D+R-, incidence was higher among recipients of non-kidney versus kidney organs (13/89 [14.6%] vs. 2/55 [3.6%], P = 0.05, respectively). Incidence in rank order was: pancreas (2/9 [22.2%]), lung (6/29 [20.7 %]), heart (2/21 [9.5%]), and liver (3/30 [6.7%]). PTLD histopathology was monomorphic in 9/15 [60%] and EBV-encoded RNA-1 (EBER-1) positive in 12/12 evaluable cases. Outcomes among the 15 PTLD cases included: graft failure without transplant in 3 (20%), graft failure with re-transplant in 2 (13.3%), and death within 6 months in 3 (20%).Table 1: Characteristics of the EBV Donor seropositive, Recipient seronegative (D+R-) cohort Figure 1: Cumulative Incidence of PTLD among the EBV D+R- cohort (all organs) Figure 2: Incidence of PTLD among the D+R- cohort, stratified by organ transplant type ConclusionAlthough rare overall, we identified a specific subgroup of adult SOT patients (EBV D+R- non-kidney recipients) whose absolute PTLD incidence and associated morbidity and mortality are high, and who should be targeted for future mechanistic or therapeutic studies.Disclosures All Authors: No reported disclosures

Post-transplant lymphoproliferative disorder after paediatric liver transplantation.

The purpose of this study was to analyse the clinical and pathological characteristics, treatments and outcomes of post-transplant lymphoproliferative disorder (PTLD) in paediatric liver transplant recipients. A retrospective analysis of records from nine paediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from June 2013 to August 2018. Of these nine patients, seven received liver transplantation in our centre and the remaining two patients at other hospitals. The overall incidence of PTLD in paediatric liver transplant recipients in our centre was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B-cell lymphoma and one was classical Hodgkin lymphoma-like PTLD. These patients presented with different clinical manifestations including fever, anaemia, diarrhoea, hypoproteinaemia, enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV-DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti-CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R-CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow-up. One patient died as a result of PTLD progression. PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti-CD20 antibody, surgery, radiotherapy and chemotherapy.

Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: Analysis of ISHLT Registry

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication following lung transplant. We studied incidence and risk factors for PTLD in adult lung transplant recipients (LTRs) using the International Society for Heart and Lung Transplantation Registry. The International Society for Heart and Lung Transplantation Registry was used to identify adult, first-time, single and bilateral LTRs with at least 1 year of follow-up between 2006 and 2016. Kaplan-Meier method was used to describe the timing and distribution of PTLD. Univariable and multivariable Cox proportional hazards regression models were used to examine clinical characteristics associated with PTLD. Of 19,309 LTRs in the analysis cohort, we identified 454 cases of PTLD. Cumulative incidence of PTLD was 1.1% (95% CI = 1.0%-1.3%) at 1 year and 4.1%(95% CI = 3.6%-4.6%) at 10years. Of the PTLD cases, 47.4% occurred within the first year following lung transplantation. In the multivariable model, independent risk factors for PTLD included age, Epstein-Barr virus serostatus, restrictive lung diseases, and induction. Risk of PTLD during the first year after transplant increased with increasing age in patients between 45 and 62 years at time of transplantation; the inverse was true for ages <45 years or >62 years. Finally, receiving a donor organ with human leukocyte antigen types A1 and A24 was associated with an increased risk of PTLD, whereas the recipient human leukocyte antigen type DR11 was associated with a decreased risk. Our study indicates that PTLD is a relatively rare complication among adult LTRs. We identified clinical characteristics that are associated with an increased risk of PTLD.

Recurrent JAK3 Mutations in Post-Transplant Lymphoproliferative Disorder

Post-transplant lymphoproliferative disorders (PTLD) are diverse in morphology, immunophenotype and clinical outcomes, occurring in immune compromised patients after hematopoietic stem cell transplantation (HCT) or single organ transplantation (SOT). Predicting the outcome of PTLDs is complex. In most of cases PTLD is driven by Epstein-Barr virus (EBV) infection, though the etiology of EBV negative cases is unknown. There have been only few studies investigating the mutational landscape and gene expression of PTLD. In our study we performed targeted DNA deep sequencing and RNA expression profiling (RNA-Seq) on the hematopoietic lymphoid tissues of 15 post-transplant patients with PTLD and 16 post-transplant patients with follicular hyperplasia (FH) after HCT or SOT. Recurrent mutations in JAK3 were identified in five of 16 PTLD cases and one of 16 follicular hyperplasia cases. We additionally identified mutations in the PIK3CD gene in four PTLD cases and NOTCH1 mutations in 2 PTLD and four FH cases. 17 other genes were commonly mutated in both groups. Gene expression profiles differed between both groups. Genes involved in regulating the immune system were unregulated in PTLD. We also saw a stronger expression of T-cells and a weaker expression of B-cells within the PTLD group when compared with FH. Our findings suggest an important role for immune regulatory pathways in the pathogenesis of PTLD, with the JAK/STAT pathway being a central recurrent key metabolic pathway. Figure Disclosures Ohgami: Agilent technologies: Other: received support/funding.

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients.

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein-Barr virus (EBV) mismatched (D+/R-) transplants and 12 from EBV-positive recipients (R+). Recipients with D+/R- matches were at a significantly higher risk of developing PTLD than R+ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Epstein-Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.

High Incidence but Very Low Mortality of Epstein Barr Virus Related Post-Transplantation Lymphoproliferative Disorder after T-Cell Replete Haploidentical Peripheral Blood Stem Cell Transplantation

BACKGROUNDThe use of immunosuppressive agents such as antithymocyte globulin (ATG) as graft-versus host disease (GVHD) prophylaxis may increase the risk of Epstein Barr Virus (EBV) related post-transplant lymphoproliferative disorder (PTLD). The aim of the present study is to report the incidence, risk factors, and outcome of PTLD in the setting of haploidentical stem cell transplant (haploSCT) combining PTCy and ATG as GVHD prophylaxis.METHODSFrom August 2016 to May 2018, 55 adult patients diagnosed with hematological malignancies underwent T-cell replete haploSCT. All patients received a reduced intensity conditioning regimen (RIC) with fludarabine, busulfan, and 200cGy of total body irradiation (TBI), combined with rabbit ATG, PTCy and cyclosporine (Cy).EBV titre was monitored by quantitative PCR in plasma samples. The cut-off value for test positivity was >600 copies of EBV DNA per milliliter of plasma. Testing was performed weekly from engraftment to day 100 and beyond in case the patients were on immunosuppression.Data was collected through retrospective chart review. Last follow up was updated in June 31, 2018. Median follow-up was 9.5 months (range 1-21).RESULTSPatient and donor characteristics are summarized in Table 1. Median age was 57 (22-73) years, with 23 (43%) patients ≥60 years. Overall survival of the 55 patients at 6 months was 70% (95% CI 57-83), and 51% (95% CI 46-66) at 1 year.EBV reactivation was documented in 31 (57%) patients. Median time to EBV reactivation was 54 (20-326) days. Three (5.5%) patients developed presumed PTLD with EBV-viremia higher than 1x10E6 copies and corroborative imaging. Three (5.5%) had biopsy-proven PTLD (Table 2). Median time since EBV reactivation to presumed/proven (P/P)-PTLD was 25 (3-36) days. All cases occurred early post-transplant within the first 100 days. Four patients were on therapeutic doses of cyclosporine. All 6 (11%) patients received treatment with weekly Rituximab 375 mg/m+. Five (83%) patients achieved complete clinical responses with PCR negativity with reduction of immunosuppression and single agent rituximab. One patient died of complications of viral encephalitis and bacterial pneumonia.CONCLUSIONATG based conditioning can be associated with increased viral reactivations. Frequent EBV monitoring and pre-emptive treatment may lead to rapid disease control. While no guidelines exist currently, further investigation is needed to define optimal monitoring strategies. [Display omitted] DisclosuresLipton:BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

Post‑transplant lymphoproliferative disorder in hematopoietic stem cell transplant patients: A single center retrospective study between 2005 and 2012.

Post‑transplant lymphoproliferative disorder (PTLD), despite its rarity, is an important mortality/morbidity event in transplant patients. The purpose of the present study was to retrospectively examine the clinical and pathologic characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of Porto. A retrospective review of patient information was performed for patients that developed PTLD following allogeneic hematopoietic stem cell transplant (aHSCT) and were diagnosed between 2005and2012. The present study included a total of 15patients, 8females (53.3%) and 7males (46.7%), with different clinicopathological characteristics. The most frequent clinical condition inducing aHSCT was acute lymphocytic leukemia (40.0%). Conditioning regimens consisted primarily in busulfan and cyclophosphamide, with anti‑thymocyte globulin, and myeloablation was the preferential treatment. Epstein‑Barr virus (EBV) was present in all patients with a median time of diagnosis following transplant of 75days (range, 25‑485days) and a median viral load of 4.75log10copies/ml (range, 3.30‑6.26log10copies/ml). PTLD diagnosis was mainly assessed by clinical findings, and histological confirmation was available for 5patients: 3monomorphic, 1polymorphic and 1with early lesions of PTLD. To the best of our knowledge, this is the first study to describe PTLD cases in HSCT patients in Portugal. The data reinforces the importance of performing EBV monitoring in high‑risk patients, particularly those receiving a transplant from mismatch/unrelated donors, and those with myeloablative conditioning regimen including antithymocyte globulin. The results also suggested that EBV viral load may be significant for the prediction of PTLD development.

Posttransplant Lymphoproliferative Disorder in Liver Transplant Recipients

Objective This study was conducted to analyze the clinical characteristics, treatment and outcome of posttransplant lymphoproliferative disorder(PTLD) in liver transplant recipients. Methods: This study includes a retrospective data analysis of nine liver transplant recipients with PTLD who were treated at the Liver Transplant Center, Beijing Friendship Hospital, China, from 2013 to 2017. One patient was adult, and the others were children. Demographic, clinical, treatment data and outcome were collected. Results The incidence of PTLD in our liver transplant center was 7/634(1.1%),whereas the incidence of PTLD in pediatric liver transplant recipients in our liver transplant center was 6/403(1.5%).All the patients were diagnosed by pathology. Three cases were classified as early lesions of PTLD,2 cases were polymorphic PTLD, two cases were burkitt lymphoma, one case was diffuse large B cell lymphoma and one case was classical Hodgkin lymphoma-like PTLD.The mean onset time was 15months after liver transplantation (from 5 to 32 months. The paitents had different clinical manifestations mainly including fever, anemia, diarrhea, enlargement of lymph nodes or hepatosplenomegaly, jaundice, intestinal obstruction and even intestinal perforation. All the patients had positive EB-DNA in serum. After the diagnosis,immunosuppressants were reduced or discontinued.All the patients received anti-CD20(Rituximab) theraphy.Four cases were treated combined with chemotheraphy(R-CHOP,ABVD,COPP/ABV).Two cases were treated combined with radiotherapy.Two cases received surgical treatment due to intestinal obstruction.Seven patients achieved complete response and were alive at the time of review. One patient died of graft failure,and another patient died of relapse of PTLD. Conclusion PTLD is one of the most serious and fatal complications after liver transplantation.The detection of EB-DNA load and imaging examination can provide clues for diagnosis.Definite diagnosis can be made based on histopathology.Treatment varies according to differet classifications,and basically including immunosuppression reduction,anti-CD20 antibody,operation, radiotherapy and chemotherapy.Early detection and early-stage treatment are needed to rescue patients who have suffered from PTLD.

Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD. We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined. At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Intrathecal Rituximab for EBV-Associated Post-Transplant Lymphoproliferative Disorder with Central Nervous System Involvement Unresponsive to Intravenous Rituximab-Based Treatments: A Prospective Study

▪Backgroud:Although the introduction of rituximab as a first-line treatment has improved outcome of post-transplant lymphoproliferative disorder (PTLD), PTLD with central nervous system involvement (CNS-PTLD) still has a dismal prognosis because of low penetrance across the blood-brain barrier. In this prospective study, we reported intrathecal rituximab was efficacy and safety in the patients with CNS-PTLD who had failed to respond to the intravenous rituximab-based treatments.Methods:From June 2009 to November 2013, 32 cases of EBV-associated PTLD were recorded in the Southern Medical University Institute of Hematology. Fourteen patients diagnosed with CNS-PTLD were enrolled in this prospective study. For the patients who failed to response to the initial intravenous rituximab-based treatments, sequential dose-escalation schedule of intrathecal rituximab (initial dose of 20mg, increased by 10mg each week and maximum dose of 50 mg) was administrated weekly.Results:Three patients were responsive and 11 were unresponsive to the initial treatments within one week after the treatments. For the 11 patients who failed to respond to the initial treatments, 9 patients received intrathecal rituximab within 7-11 days and 2 patients refused the treatment. After two cycles of rituximab-based treatments, 10 patients achieved complete response (CR), 2 patients were partial response and 2 patients were non-response. With a median follow up of 664 (range 18 to 1545) days after the diagnosis of CNS-PTLD, 7 patients survived and 7 died. The causes of death included PTLD progressing (n=3), PTLD relapse (n=1), GVHD (n=1), CMV pneumonia (n=1) and pseudomonas aeruginosa sepsis (n=1). The 3-year probability of OS was 45.7% ±14.7% in CNS-PTLD, which was no significant difference as compared to PTLD without CNS involvement(55.6% ±11.7%, P=0.706).Conclusion:Intrathecal rituximab might be an effective and safe method for CNS-PTLD in the allo-HSCT recipients who were unresponsive to the intravenous rituximab-based treatments. DisclosuresNo relevant conflicts of interest to declare.

Post-transplant lymphoproliferative disorder in liver recipients: Characteristics, management, and outcome from a single-centre experience with >1000 liver transplantations.

The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited. To study the incidence, predictors and outcomes of PTLD after liver transplantation in a single, large-volume centre. The charts of all LTRs (n=1372) in the authors' centre between January 2000 and June 2012 were retrospectively reviewed and those who developed PTLD were identified. Demographic, clinical and treatment data were prospectively collected. Responses to treatment, including complete response, no response, relapse and survival, were recorded. The incidence of PTLD in LTRs was 32 in 1372 (2.3%). Overall, median survival was 37 months (range 0.5 to 195 months), with one-, three- and five-year survival rates of 81%, 74% and 60%, respectively. Epstein-Barr virus (EBV)-negative patients had a better mean (± SD) survival (95±79 months) than EBV-positive patients (41±42 months) (P=0.02). For stage I⁄II PTLD, one-, three- and five-year actuarial survival was 87%, 87% and 75%, compared with 50%, 30% and 0% for stage III⁄IV PTLD, respectively (P=0.001). In patients with complete response, median survival was 58 months (range 10 to 195 months); and one-, three- and five-year actuarial survival was 100%, 94% and 76%, respectively, after diagnosis of PTLD. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival (seven of seven survivors) compared with only decreasing or stopping IS (14 of 25 survivors) (P=0.07). This series from a single large-volume centre showed excellent short and long-term survival after PTLD in adult LTRs who were EBV negative, had early disease and showed complete response. Consistent with the known in vitro antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival.

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

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