Transplant Lymphoproliferative Disorder Research Articles

P.491: Post transplant lymphoproliferative disorder in pediatric solid organ transplant recipients: A seven-year single-center analysis.

P.491: Post transplant lymphoproliferative disorder in pediatric solid organ transplant recipients: A seven-year single-center analysis.

#516 Cancer after kidney transplantation in the single transplant center

Abstract Background and Aims A retrospective analysis of peculiarities of development of malignant neoplasms in patients after kidney transplantation receiving long-term immunosuppression. Method In this study we evaluated incidence of malignancies observed among 718 renal transplant recipient with at least 6 months of follow-up. A total of 561 men and 257 women, mean age at transplantation 36.3 ± 8.3 years were included. Results Thirty-three out of 718 recipients (4.6%) developed malignant neoplasia: 45.5% of these were Kaposi's sarcomas, 12.1%—cancers of the uterine cervix, 12.1% cancer of the stomach, 12.1% - basal cell carcinomas, 6.06% - post transplant lymphoproliferative disorder. There was no significant effect of either cyclosporine A, tacrolimus doses or OKT3/ATG on the incidence of the tumors. The median time from onset of end-stage renal failure (dialysis start) and from the transplantation to the diagnosis of the tumor make up 32 (16-161) and 23 (5-158) mouths, respectively. One renal transplant recipient suffered from multiple myeloma with aggressive course. Three patients diagnosed with renal cell carcinoma of the transplant: clear cell carcinoma, papillary carcinoma, mucinous adenocarcinoma via 264, 24 and 4 months respectively. Conclusion The importance of strict adherence to intensive monitoring transplant patients, which can detect tumors at an early stage. Strict adherence to intensive follow-up of transplant patients is important, which makes it possible to identify neoplasms at an early stage, when organ-preserving treatment is feasible and effective. In addition, modification of immunosuppressive therapy in such patients involves reducing the dose or, if possible, completely eliminating calcineurin inhibitors and starting taking mTOR inhibitors (sirolimus or everolimus), taking into account the antitumor effect of this group of immunosuppressants.

The Effect of Preemptive Rituximab Treatment in Patients with EBV Viremia after Solid Organ Transplantation on the Development of Post-Transplant Lymphoproliferative Disorder

The association between Epstein-Barr Virus (EBV) reactivation after solid organ transplantation (SOT) and Post-Transplant Lymphoproliferative Disorder (PTLD) is well described. There are currently no guidelines regarding the use of rituximab preemptively in patients with EBV viremia after SOT to reduce the risk of PTLD. We sought to determine whether rituximab in SOT patients with EBV viremia has benefit in preventing PTLD. This retrospective analysis of electronic medical record data identified SOT recipients who experienced EBV viremia post-transplant between January 2010 and February 2023 at Columbia University Irving Medical Center (CUIMC). Data queries were clinically reviewed. Logistic regression analysis was performed to investigate the relationship between predictor variables including rituximab administration, log-transformed EBV peak titer, duration of EBV viremia, and time from SOT to EBV reactivation, with the binary primary outcome of PTLD diagnosis status. The analysis encompassed both univariate and multivariate logistic regression. There were 2,168 patients who met the inclusion criteria of having EBV reactivation after SOT, out of 6,395 total SOT performed at CUIMC during this timeframe. Patient characteristics are described in table 1. The median peak EBV titer was 154 (range: not quantifiable - 5,335,816), the median duration of EBV viremia was 78 days (range: 1 - 6,980), and the median time from SOT to EBV reactivation was 688 days (range: 0-11103). Of the 2,168 patients, 185/2168 (8.5%) received rituximab for indications other than PTLD including EBV viremia, treatment of rejection, antibody desensitization therapy/immunosuppression peri-transplant, and other non-transplant related indications (e.g. lupus nephritis). Of the patients who received rituximab, 182/185 (98.4%) did not develop PTLD. The 3/185 (1.6%) patients who did develop PTLD were all ≤ 20 years-old at time of diagnosis, and had EBER(+), monomorphic PTLD, diffuse large B-cell lymphoma type, with a non-germinal center phenotype, involving the gastrointestinal tract. Two were CD20 positive, all 3 had partial weak CD30 positivity, and all 3 had clonal immunoglobulin heavy chain rearrangements. Among the patients who did not receive preemptive rituximab post-SOT, 195/1983 (9.8%) developed PTLD, whereas 1788/1983 (90.2%) did not. Prior rituximab therapy for any indication in patients with EBV viremia post-SOT was associated with lower risk of subsequent PTLD by univariate analysis (0.14% vs 8.39%, OR 0.15, p = 0.0013, 95% CI 0.048-0.48). Receipt of rituximab (OR 0.12, p=0.0002), log-transformed peak EBV titer (OR 1.10, p<0.0001), and duration of EBV viremia in months (OR 1.01, p<0.0001) were all independently associated with risk for PTLD by multivariate analysis (figure 1). The relationship between time from SOT to EBV viremia was not significantly associated with development of PTLD. This retrospective analysis suggests that administering preemptive rituximab in SOT patients with EBV viremia may lower the risk of developing PTLD. The fact that peak EBV titer and duration of EBV viremia remain associated with PTLD in multivariate analyses suggests that the benefit of rituximab may be independent of the degree or duration of EBV viremia. A prospective analysis of factors such as area under the curve of EBV exposure, HLA status, T cell clonotype diversity, organ type, and immunosuppression type, is needed to better understand individual risks for improved selection of those who would benefit from preemptive rituximab.

A case of post renal transplant PTLD of lung.

Post Transplant Lymphoproliferative Disorder (PTLD) is a heterogeneous group of Lymphoid proliferative disorders that occur in patients post Hematogenous or Solid organ transplants. They are closely associated with Ebstein-Barr Virus and can range from polyclonal lesions to frank lymphomas. PTLD is usually a rare post-transplant complication, with the incidence being higher post Lung or Heart Transplantation and less commonly seen post-renal transplantation. The incidence post renal transplantation is less than 1%, with most of the cases being limited to the Gastro-Intestinal Tract and Lymph nodes, and incidence in the lungs being extremely rare. Here we present a case report of PTLD of the lung in a post-renal transplant recipient.

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

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

EBV-encoded miRNAs BHRF1-1 and BART2-5p aggravate post- transplant lymphoproliferative disorder via LZTS2-PI3K-AKT axis

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications after transplantation. Epstein-Barr virus (EBV) is a key pathogenic driver of PTLD. About 80% of PTLD patients are EBV positive. However, the accuracy of preventing and diagnosing EBV-PTLD by monitoring EBV DNA load is limited. Therefore, new diagnostic molecular markers are urgently needed. EBV-encoded miRNAs can regulate a variety of EBV-associated tumors and are expected to be potential diagnostic markers and therapeutic targets. We found BHRF1-1 and BART2-5p were significantly elevated in EBV-PTLD patients, functionally promoting proliferation and inhibiting apoptosis in EBV-PTLD. Mechanistically, we first found that LZTS2 acts as a tumor suppressor gene in EBV-PTLD, and BHRF1-1 and BART2-5p can simultaneously inhibit LZTS2 and activate PI3K-AKT pathway. This study shows that BHRF1-1 and BART2-5p can simultaneously inhibit the expression of tumor suppressor LZTS2, and activate the PI3K-AKT pathway, leading to the occurrence and development of EBV-PTLD.Therefore, BHRF1-1 and BART2-5p are expected to be potential diagnostic markers and therapeutic targets for EBV-PTLD patients.

Lymphoproliferative disorders after renal transplantation along 2 decades: a large longitudinal study of 21.546 recipients

IntroductionPost transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors. Material y methodsWe have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. ResultsA total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent.During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (n = 91, 52,9%), followed by sepsis (n = 24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years.The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years.Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods. ConclusionPTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.

Decoding the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders

AbstractPosttransplant lymphoproliferative disorders (PTLDs) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLDs) has not been elucidated, and it is unknown whether they display similar genetic features as their counterpart in adult and immunocompetent (IMC) pediatric patients. In this study, we investigated 31 cases of pediatric mPTLD after solid organ transplantation, including 24 diffuse large B-cell lymphomas (DLBCLs), mostly classified as activated B cell, and 7 cases of Burkitt lymphoma (BL), 93% of which were EBV positive. We performed an integrated molecular approach, including fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. Overall, PTLD-BL carried mutations in MYC, ID3, DDX3X, ARID1A, or CCND3 resembling IMC-BL, higher mutational burden than PTLD-DLBCL, and lesser CN alterations than IMC-BL. PTLD-DLBCL showed a very heterogeneous genomic profile with fewer mutations and CN alterations than IMC-DLBCL. Epigenetic modifiers and genes of the Notch pathway were the most recurrently mutated in PTLD-DLBCL (both 28%). Mutations in cell cycle and Notch pathways correlated with a worse outcome. All 7 patients with PTLD-BL were alive after treatment with pediatric B-cell non-Hodgkin lymphoma protocols, whereas 54% of patients with DLBCL were cured with immunosuppression reduction, rituximab, and/or low-dose chemotherapy. These findings highlight the low complexity of pediatric PTLD-DLBCL, their good response to low-intensity treatment, and the shared pathogenesis between PTLD-BL and EBV-positive IMC-BL. We also suggest new potential parameters that could help in the diagnosis and the design of better therapeutic strategies for these patients.

(25) Machine Learning Ensemble Models for Predicting Post- Transplant Lymphoproliferative Disorder in Heart Transplant Recipients

(25) Machine Learning Ensemble Models for Predicting Post- Transplant Lymphoproliferative Disorder in Heart Transplant Recipients

Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study.

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.

Home palliative care for a patient with post-lung transplant lymphoproliferative disorder: A case report

Home palliative care for a patient with post-lung transplant lymphoproliferative disorder: A case report

Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens

BackgroundBelatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone. MethodsThe records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B0, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B1, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed. ResultsThere were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B0: 67.48 vs. B1: 59.10, p = 0.0014). Graft failure at 12 (B0: 1.28% vs. B1: 0.84%, p = 1.0) and 24 months (B0:2.55% vs. B1: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B0: 1.27% vs. B1: 2.52%, p = 0.408) or 24 months (B0: 2.12% vs. B1: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia. ConclusionNon-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.

Identifying Demographic and Disease Related Differences in Hispanic Vs Non-Hispanic Patients with Post Transplant Lymphoproliferative Disorders

Identifying Demographic and Disease Related Differences in Hispanic Vs Non-Hispanic Patients with Post Transplant Lymphoproliferative Disorders

The Outcome of Cytotoxic-T-Lymphocytes and Brentuximab on Post Transplant Lymphoproliferative Disorder: A Systematic Review and Meta-Analysis

Introduction: Epstein-Bar-Virus (EBV) associated post-transplant lymphoproliferative disorder (PTLD) is associated with increased mortality and morbidity in solid organ and hemopoietic-stem-cell (HSC) transplant recipients. Conventionally, it was being treated with reduction in immune suppressants, rituximab (Rx), chemotherapy, or radiotherapy. However, given the relapse-refractory (RR) nature of the disease, other agents such as EBV specific cytotoxic T-lymphocyte (EBV-CTL), brentuximab are being used with some success. In this review, we will assess the efficacy of such agents in PTLD. Method: We performed literature search from 3 databases (PubMed, Embase and Web of Science) using the MeSH terms and keywords ''Post Transplant Lymphoproliferative Disorder'' and ''Treatment Outcome''. After excluding the duplicates, we conducted primary and secondary screening on 1564 studies, and finalized 9 studies for the meta-analysis (4 prospective studies, 2 retrospective studies, and 3 phase I/II clinical trials). Subgroup analysis was performed by using the OpenMetaAnalyst software, and quality evaluation was performed with the help of NIH quality assessment tool. Results: We conducted meta-analysis on 67 patients from 9 studies, of which 29 (43.3%) were treatment-naïve, and 38 (57%) were RR. 59 (88%) received EBV-CTL, and 8 (12%) received brentuximab, either as a monotherapy in treatment-failure cases or as a combination therapy in naïve cases. For the EBV-CTL subgroup, the pooled complete response (CR) was 60.4% (95% CI 0.290-0.886, I²= 59.41%, p=0.031), pooled partial response (PR) was 10% (95% CI 0.002-0.270, I²= 0%, p=0.833), and pooled mortality was 24% (95% CI 0.026-0.534, I²= 30.3%, p=0.230). For brentuximab subgroup, the pooled CR was 55.2% (95% CI 0.118-0.986, I²= 42.98%, p=0.185), and pooled mortality was 34.3% (95% CI 0.165-0.537, I²= 58.94%, p=0.012). The common adverse effects seen from these therapies are graft-versus-host-disease and infection, however, given the heterogeneity, we could not perform pooled analysis. Conclusion: There is no standard guideline available to treat RR PTLD. We conclude that CTL and brentuximab could be an appropriate second-line therapy in treatment failure cases or could be used concomitantly with rituximab for better patient outcome. Clinical trials with longer follow ups need to be conducted to assess safety and efficacy of these agents. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Acute Kidney Injury in a Patient With a Kidney Transplant and Posttransplant Lymphoproliferative Disorder: A Quiz

A 36-year-old woman with a living donor kidney transplant from her sister 6 years ago presented with a serum creatinine of 1.9 mg/dL, from a baseline of 0.5 mg/dL 1 week prior to presentation. She had received the transplant after reaching kidney failure due to focal segmental glomerulosclerosis and she had been diagnosed with posttransplant lymphoproliferative disorder (PTLD) 2 years ago. Despite completion of therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and subsequently ICE (ifosfamide, carboplatin, etoposide) 6 months ago, she experienced PTLD progression and new hypermetabolic lesions involving the liver and spleen were seen 1 month ago.

P8.085: Outcomes of Post Kidney Transplant Lymphoproliferative Disorder (PTLD)

P8.085: Outcomes of Post Kidney Transplant Lymphoproliferative Disorder (PTLD)

Successful eradication of rituximab-refractory EBV-related post- transplant lymphoproliferative disorder after second haplo-identical allogeneic hematopoietic stem cell transplantation for very severe aplastic anemia – a case report

EBV-related post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal disorder arising after solid organ or hematopoietic stem cell transplant (HSCT). The principle of management includes reduction of immune suppression, rituximab, and chemotherapy. We presented a female patient of very severe aplastic anemia (VSAA) complicated with initial graft dysfunction and then graft failure 2 months after haplo-identical allogeneic HSCT, with no response to salvage cyclosporine plus eltrombopag. EBV-related PTLD occurred 6 months after first haplo-transplant as shown by high EBV PCR. The patient initially responded to 6 shots of weekly rituximab, and then progression to ultrahigh level of EBV DNAemia was observed with the presence of intra-hepatic PTLD that was refractory to rituximab. This patient subsequently underwent second haplo-identical allogeneic transplant from the same donor with megadose of stem cell number plus alkylating agent containing RIC regimen. The results were successful hematopoietic engraftment on day +15, clearance of EBV DNAemia in one month, and thereafter eradication of intra-hepatic EBV-PTLD. In conclusion, EBV-related PTLD refractory to rituximab alone is still sensitive to rituximab plus chemotherapy preparative regimen during subsequent allogeneic HSCT, and it is still feasible to perform allo-transplant for transplant-eligible patients despite the presence of rituximab-refractory EBV DNAemia and PTLD.

Pediatric EBV-negative monomorphic post–solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers.

10012 Background: Pediatric EBV(-)M-PTLD comprises < 15% of M-PTLD. Two-year-overall survival of pediatric EBV(+) PTLD is 83%. No large multi-institution pediatric-specific reports are available for EBV(-)M-PTLD. Methods: Retrospective study of characteristics, treatment, and outcome of pediatric solid organ recipients diagnosed with EBV(-)M-PTLD at age ≤21 years (y) in 11 pediatric transplant centers in US and UK. Results: Thirty-three patients transplanted with solid organs between 1991-2017 developed EBV(-)M-PTLD. Twenty-two (66%) were male. Median age (range) at organ transplantation was 2.6y(0.1-17), diagnosis of EBV(-)M-PTLD 14y(3-20), interval from transplant to PTLD 8.3y (2.3-18). Transplanted organs were heart (n = 10), kidney (n = 17), liver (n = 4), small bowel (n = 1), liver and small bowel (n = 1). Immunosuppressive therapy at the time of diagnosis of PTLD was available on 31 patients. All were receiving a calcineurin inhibitor except one who was on sirolimus alone. Tacrolimus was given in 27 patients, alone (n = 3), or in various combination with mycophenolate (n = 8), azathioprine (n = 9), prednisone (n = 8), or everolimus (n = 1). Four of these receiving tacrolimus received 3 immunosuppressive drug combinations. Cyclosporine was given in 3 patients, with mycophenolate (n = 1), prednisone (n = 1), or both (n = 2). Murphy stages were I (n = 1), II (n = 7), III (n = 22), and IV (n = 3). Lactate dehydrogenase was elevated in 19/31 (61%) and > 2X upper limit of normal in 10/31 (32%) tested. Pathological diagnoses were diffuse large B-cell lymphoma (n = 30) and B-NHL NOS (n = 3). Treatment included: rituximab alone (n = 1), low-dose cyclophosphamide, prednisone, and rituximab (CPR; n = 9), pediatric mature B-NHL-specific regimen [FAB/LMB with (n = 12) or without (n = 1) rituximab], EPOCH-R (n = 2), R-CHOP (n = 3), modified R-CHOP (n = 2), COP (n = 1), and R-COP (n = 2). At a median 2.9y (0.3-11y) from diagnosis, 26/33 (79%) were alive and in complete remission (CR). Three experienced relapses at 1, 3, and 6.5y after CPR, rituximab alone, and B-NHL therapy, respectively. All achieved a sustained second CR with additional B-NHL therapy. Of the 7 deaths: 6 were from progressive disease despite escalation to intensive B-NHL therapy following initial COP (n = 1), R-COP (n = 1), CPR (n = 2), and B-NHL therapy (n = 2), and one cardiac transplant recipient from presumed cardiotoxicity. There was one graft rejection that was successfully treated. Conclusions: This collaboration represents the first multi-institution series of pediatric EBV(-)M-PTLD. Overall survival was comparable to that reported for pediatric EBV(+) PTLD, but inferior to DLBCL in immunocompetent children. These preliminary data reflect a wide range of therapeutic regimens used over 20 years and strongly support an organized collaborative effort to collect data prospectively.

RAPIDLY PROGRESSIVE POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER AFTER LUNG TRANSPLANTATION

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) after lung transplantation occurs due to immunosuppressant therapy, which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and B cell transformation. CASE PRESENTATION: A 67-year-old female, bilateral lung transplant recipient (07/2019) with a history of idiopathic pulmonary fibrosis developed rapidly progressive PTLD in the early postoperative course. DISCUSSION: At 6-months after transplant, chest radiographs revealed left hilar fullness; subsequent chest CT showed evidence of fluid in the fissure, with no obvious lymphadenopathy. Chest CT performed just two weeks later revealed a left hilar mass measuring 6.1 × 2.7 cm with encasement of the left main pulmonary artery and partial collapse of the left main bronchus. Endobronchial ultrasound-guided biopsies led to the diagnosis of CD20-positive, EBV-positive PTLD. Initial PET scan demonstrated multiple hilar lymph nodes, the largest measuring 2.2 × 2.8 cm. Immunosuppression was reduced, and because the PTLD involved only one area in an EBV-mismatched bilateral lung transplant recipient, she qualified for single-agent rituximab once/week. Unfortunately, repeat imaging after five doses of rituximab demonstrated significant disease progression. She required repeat bronchoscopy with tumor debulking for a necrotic, endobronchial tumor occluding up to one-half of the left lower lobe bronchus. She started R-mini-CHOP, and after three cycles of chemotherapy, complete response was observed on the most recent PET/CT scan. CONCLUSIONS: PTLD may progress quickly, as the initial chest CT scan showing fluid collection advanced rapidly into a hilar mass. Reduction in immunosuppression, anti-CD20 biologic therapy, and chemotherapy for refractory PTLD remains an appropriate treatment paradigm. DISCLOSURE: Nothing to declare. KEYWORD: Post-lung transplant lymphoproliferative disorder

A Machine Learning Model for Post-Transplant Lymphoproliferative Disorder Using the UNOS Database

<h3>Purpose</h3> Post Transplant Lymphoproliferative Disorder (PTLD) is a complication noted in cardiac allograft recipients. This study was undertaken to generate a risk prediction model for PTLD at 1, 3 and 5 years post heart transplant using machine learning models. The United Network for Organ Sharing (UNOS) database was used for data generation <h3>Methods</h3> The UNOS database was probed from 1987 to 2015<b>.</b> After excluding retransplants and those with incomplete information regarding malignancy, 39696 adult patients were identified out of which 884 patients had PTLD. A Random Under-sampling Boosting ("RUSBoost") technique in combination with Decision Tree models ("ensemble of models") was used to create a PTLD prediction model. Random Under-sampling technique was combined with boosting (AdaBoost M2) to enhance the prediction model. Variables with higher predictive power were used for testing and training. A 5-fold cross validation was performed to train and test them on five different subsets of data. Model performance was evaluated using average Area Under the Curve (AUC) using Receiver Operating Curves (ROC) for the 5 test subsets <h3>Results</h3> The significant continuous variables for predicting PTLD were ischemic time, recipient serum creatinine, and presence of B2, DR1,DR2 antigens in recipient serum. Of the categorical variables investigated gender, diabetes in the recipient, ethnicity, CMV status of the donor and induction with azathioprine, OKT3,thymoglobulin or cyclosporine were significant. The AUCs ranged from 0.76 to 0.79 and 0.66 to 0.7 in the testing or validation batch respectively. <h3>Conclusion</h3> This is the first report of using machine learning algorithms to derive a risk prediction model for PTLD. This model has a robust AUC for predicting PTLD at years 1, 3 and 5 posttransplant. The limitations of this study are its retrospective nature and that it needs external validation.