Positive EBV Research Articles

A247 VIRAL LOAD OF EPSTEIN-BARR VIRUS IN PEDIATRIC PATIENTS WITH NEW ONSET IBD AT DIAGNOSIS AND ON FOLLOW UP: AN OBSERVATIONAL STUDY

Abstract Background Patients with Inflammatory Bowel Disease are at increased risk for complications associated with Epstein-Barr Virus, such as uncontrolled infection, colitis mimicking IBD, and lymphoproliferative disease. These complications may be due to inherent immune dysfunction or effects of immunomodulating therapies used. We have previously identified that the seroprevalence of EBV in our cohort of IBD patients at time of diagnosis was 44.2%, with prevalence stratified by age as follows: 0 to <10 years 36%, 10 to <17 years 46%, and 17 + years 50%. Aims Our objective is to assess the risk of EBV reactivation in this population, to determine whether patients treated with immunomodulators should be more closely monitored for EBV viral load. Methods Retrospective chart review was done for all patients with new-onset IBD diagnosed at CHU Sainte-Justine over a two-year period, from Jan. 2016 to Dec. 2017. Serum from time of diagnosis was retrieved from the microbiology laboratory for patients with positive EBV serology, and quantitative PCR was performed to assess viral load at diagnosis. 47 of 53 seropositive patients had available serum at time of retrieval. EBV PCR was subsequently performed on serum drawn one to two years after start of immunosuppressants. Results 53 patients were EBV positive at time of diagnosis (EBNA/VCA IgG). Two patients were IgM positive, suggesting recent or active infection. The viral load as measured by quantitative PCR on serum drawn at diagnosis was negative in all retroactively tested patients. Of the two IgM-positive patients, one had known positive quantitative PCR at time of diagnosis. PCR previously tested in clinical follow-up of two seropositive, PCR-negative patients became positive at 7 and 17 months from diagnosis, suggesting viral reactivation. Both patients had received anti-TNF’s and systemic corticosteroids. Viral loads on follow-up are to be assessed for the rest of the cohort. Overall, therapies started within 6 months of diagnosis were similar in the seropositive and seronegative groups, the majority receiving some form of immunosuppression. Within the seropositive group: 66% received corticosteroids, 32.1% Infliximab, 5.7% Adalimumab, and 5.7% Azathioprine. Conclusions Only one patient had active EBV infection with positive PCR at time of diagnosis. All other patients had no sign of active infection based on retroactive PCR’s. While a majority of patients, regardless of EBV serology, receive immunomodulating agents, we currently do not routinely screen for seroconversion in seronegative patients, or for viral load in seropositive patients. We will be assessing viral loads after start of immunomodulation to better understand the potential impact of these agents on disease progression. Funding Agencies None

The value of plasma EBV DNA in monitoring the therapeutic effect of nasopharyngeal carcinoma

Objective To investigate the clinical value of plasma EBV DNA in monitoring clinical efficacy in the treatment of nasopharyngeal carcinoma (NPC). Methods Clinical data of 799 patients initially diagnosed with NPC treated with radical intensity-modulated radiotherapy (IMRT) in our hospital from 2016 to 2017 were analyzed retrospectively. Prior to treatment, the correlation between plasma EBV DNA, clinical stage and tumor progression was analyzed. The relationship between EBV DNA and tumor progression was analyzed after radiotherapy and during follow-up. Results Before IMRT, the level of EBV DNA was positively correlated with both clinical stage and tumor progression (both P<0.001). At 6 to 8 weeks after IMRT, 19(2.3%) patients positive for plasma EBV DNA obtained the worst prognosis and 14 cases had tumor progression. At 6-8 weeks after IMRT, 9 patients were negative for EBV DNA and 3 cases had tumor progression. The tumor progression rate of patients with undetectable plasma EBV DNA at the end of IMRT was only 8.3%(64/772), and the progression-free survival rate significantly differed among three groups (all P<0.05). The sensitivity, specificity and accuracy rates of persistent positive plasma EBV DNA during follow-up were calculated as 77.6%, 100% and 98.1%, respectively. Conclusions The level of plasma EBV DNA in patients with NPC is correlated with tumor bearing and tumor progression prior to IMRT. At 6-8 weeks after IMRT, patients who are persistently positive for EBV DNA obtain the worst prognosis and should be given with appropriate adjuvant therapy. The correlation between persistent positive plasma EBV DNA during follow up and tumor progression yields a high accuracy rate, indicating that plasma EBV DNA is a reliable biomarker for monitoring the clinical efficacy after radical treatment for NPC patients. Key words: Nasopharyngeal neoplasm/intensity-modulated radiotherapy; EBV; DNA; Monitoring

Linfoma de células t periférico, no especificado. Estudio clínico-patológico en una cohorte de pacientes peruanos

Objetivos. La última clasifcación de la OMS de neoplasias hematopoyéticasy linfoides considera 29 linfomas de células T y NK maduras. Una de estas,corresponde al linfoma de células T periférico, sin otra especifcación (LCTPNOS). El objetivo de esta investigación fue evaluar las características clínicopatológicas de esta enfermedad y su asociación con infección por VEB en relación con la sobrevida global (SG). Métodos. Se estudiaron 65 casoscon diagnóstico de LCTP-NOS en el Instituto Nacional de EnfermedadesNeoplásicas, durante un periodo de 6 años. Se evaluaron las característicasclínico-patológicas y se comparó la SG y otros parámetros clínicos entre loscasos con infección y sin infección por VEB. Resultados. Hubo un 45 % decasos positivos para VEB. El promedio de edad fue de 50 años y hubo un 29 %de mujeres. La proporción de pacientes con y sin síntomas B fue similar. Losestadios fueron usualmente avanzados, con lactato deshidrogenasa elevada.El índice pronóstico internacional fue intermedio-alto o alto en la mayorparte de los casos. La SG en todos los casos a 5 años fue en promedio de un29,4 %. En general la respuesta al tratamiento con quimioterapia fue pobre.Aunque los casos VEB positivos tuvieron peor SG que los VEB negativos, ladiferencia no fue estadísticamente signifcativa. Hubo diferencia signifcativapara los síntomas B, siendo más frecuentes en los casos VEB positivos.También se encontró diferencia estadísticamente signifcativa en la SG a lostres años entre los LCTP-NOS VEB positivos con fenotipo citotóxico vs, los queno tuvieron fenotipo citotóxico. Conclusiones. El LCTP-NOS es una neoplasiade mal pronóstico, con baja SG y pobre respuesta al tratamiento conquimioterapia. Para una mejor valoración de la infección del VEB como factorpronóstico, se deben considerar la cantidad y tipo de linfocitos infectados.

Dramatic Resolution of HLH after Treatment with the JAK 1/2 Inhibitor, Ruxolitinib

Introduction: Preclincal murine models of primary and secondary hemophagocytic lymphohistiocytosis (HLH) have demonstrated the role of JAK/STAT signaling in propagating the cytokine-mediated hyperinflammatory state. Das et al. (Blood 2016) demonstrated that ruxolitinib (rux) effectively attenuates murine HLH, and Albeituni et al. (Blood 2019) found it superior to IFN-γ inhibition (the target of emapalumab-lzsg). A few single case reports exist in which rux was used for salvage therapy, however they report only limited clinical success and/or were used as a bridge to allogeneic stem cell transplantation. Here we present a series of three consecutive cases in which rux was employed as either salvage therapy for relapsed/refractory secondary HLH or front-line for moderate HLH manifestations. Importantly, each patient was maintained on a taper of rux which prevented recurrence and obviated the need for allogeneic transplantation. Two of the three patients have been tapered completely off rux without recurrence of either laboratory or clinical manifestations of HLH at the time of this submission. Case 1: Patient 1 is a 24 yo woman who had initially presented to an outside hospital with jaundice and was found to have a warm AIHA. She was initially started on steroids, but developed worsening anemia, fever, splenomegaly, and encephalopathy. On transfer to us she had ferritin of 58,505 ng/ml. Her bone marrow biopsy demonstrated abundant hemophagocytosis (Fig. 1B,C). She met HLH criteria and was started on HLH-94 protocol; however, her total and direct bilirubin climbed dramatically, peaking at 95.2 and 82.0 mg/dl, respectively. Rux 5mg BID was initiated as salvage therapy, and within 48 hours, her labs significantly improved, her fevers resolved, and she became responsive to blood transfusions (Fig. 1A). After two weeks on rux, she developed recurrent hemolysis. Her dose was increased to 20mg BID, resulting in a complete resolution of her hemolysis, fevers, transaminitis and hyperbilirubinemia. After 3 months of clinical stability, rux was tapered. She has been off rux now for three months. Case 2: Patient 2 is a 26 yo woman who presented with unremitting fevers and myalgias, and was found to have an acute hepatitis C infection. Her ferritin was 24,023ng/ml, and a bone marrow biopsy demonstrated abundant hemophagocytosis. She initially responded to the HLH-94 protocol; however, attempts to hold treatment following induction were met with recurrent fevers, encephalopathy, and hyperferritinemia. She transferred to us, and a repeat bone marrow biopsy demonstrated persistent hemophagocytosis (Fig. 2B,C), while her ferritin was 15,073 ng/ml. We initiated salvage treatment with rux 10mg BID. Her fevers, encephalopathy, and lab abnormalities quickly improved; her ferritin fell to 2,973ng/ml within 3 days (Fig. 2A). A small subsequent elevation in her ferritin prompted an increase of the rux to 20mg BID. She improved and was discharged on rux maintenance at 20mg BID. Since discharge, she remains asymptomatic with mildly elevated ferritin levels, mild pancytopenia, and is tolerating a slow wean of rux without incident. Case 3: Patient 3 is a 40 yo man with a diagnosis of hairy cell leukemia who received 5 days of cladribine. He developed febrile neutropenia 2 days following the end of chemotherapy. His infectious workup was negative with the exception of a positive peripheral blood EBV DNA PCR. He developed a mononucleosis-like syndrome, with persistent high fevers, splenomegaly, and hyperferritinemia to 6684 ng/ml. He also developed hepatic dysfunction with a direct hyperbilirubinemia peaking at 14.1 mg/dl and coagulopathy. He was treated initially with dexamethasone without resolution. A bone marrow biopsy demonstrated abundant hemophagocytosis (Fig. 3B,C). Given modest manifestations and concern that chemotherapy would exacerbate his immunosuppression, rux was initiated at 10mg BID. The liver dysfunction rapidly improved, and fevers resolved within 3 days (Fig. 3A). All other manifestations resolved within 1 week, and he was able to taper and discontinue rux within 2 months. Conclusions: The preclinical data by Albeituni et al. coupled with our clinical observations suggest that ruxolitinib may be a viable alternative to aggressive chemotherapy regimens such as HLH-94 or anti-IFN-γ (emapalumab-lzsg) therapy for HLH, and clinical trials should be considered. Disclosures DiPersio: Karyopharm Therapeutics: Consultancy; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding; Macrogenics: Research Funding, Speakers Bureau; Bioline Rx: Research Funding, Speakers Bureau; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Equity Ownership; WUGEN: Equity Ownership, Patents &amp; Royalties, Research Funding; Amphivena Therapeutics: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Consultancy. OffLabel Disclosure: Ruxolitinib was used off-label for the treatment of Hemophagocytic Lymphohistiocytosis (HLH) in the relapsed/refractory setting and in a patient who was unable to tolerate standard therapy. This was not in a clinical trial, but reported as a case series

Cell of Origin and Treatment Impact on the Outcome of Monomorphic Post-Transplant Lymphoproliferative Disorder-Diffuse Large B-Cell Lymphoma Subtype

Introduction : Cell of origin (COO) determination of diffuse large B-cell lymphoma (DLBCL) is important, as it has prognostic and therapeutic relevance. Patients with germinal center (GC) like DLBCL have more favorable outcomes than those with non-GC DLBCL, when treated with standard immunochemotherapy. In monomorphic post-transplant lymphoproliferative disorder (PTLD), DLBCL subtype, the biologic significance of COO is not well established. The aims of this study were to evaluate the impact of the COO on clinical presentation, outcome and response to different treatment regimens. Methods : We conducted a retrospective review of all monomorphic PTLD of the DLBCL subtype diagnosed and treated at Columbia University from 2000-2018. COO classification into GC and non-GC subtype was determined by immunohistochemistry using the Hans algorithm. In situ hybridization for Epstein-Barr encoded small RNAs (EBER) was performed to evaluate for EBV infection of the neoplastic lymphocytes. Outcomes according to therapeutic regimens were assessed using the revised response criteria for malignant lymphoma (2007). Overall survival (OS) and progression free survival (PFS) were estimated by the Kaplan-Meier method and compared by the log rank test. Results : Cell of origin: Biopsy material for COO subtyping was available for 49 monomorphic PTLD-DLBCL diagnosed during the study period. By immunohistochemistry 20/49 cases (40.8%) were GC and 29/49 cases (59.2%) were non-GC. Median age of presentation was 52 years (range 3-72) and 55 years (range 3-75), for the GC and non-GC respectively. Median time from transplant to PTLD onset was 3 years, range 7 months-25 years vs. 6 years, range 2 months-24 years for GC vs non-GC respectively. There was no significant difference in the incidence of EBV positivity, immunosuppressive therapy, organ transplanted, stage, LDH, ECOG and IPI between the 2 groups. Of note, extranodal involvement, specifically of the gastrointestinal tract was extremely common in both subtypes (16/20 [80%] in GC and 25/29 [86%] in non-GC). While acknowledging the heterogeneity of therapies administered, a trend suggesting better prognosis for the GC type was noted, although not statistically significant. The median PFS was 151.0 months for GC vs 17.0 months in non-GC (p= 0.1095), while the median OS was 151.0 months for GC vs 36.7 months for non-GC (p=0.1006) (Figure 1A, 1B). Impact of Treatment: Of the 49 cases, 44 were adults (age≥18). The two most common first line therapies administered were R-EPOCH (25) and R-CHOP (9). Ten patients received 6 other therapies including Rituximab monotherapy (3), CHOP (2), palliative care (2), RCEOP (1), EPOCH (1), and radiation (1). When focusing on patients who received R-CHOP or R-EPOCH as initial therapy, no significant differences in age, stage, LDH, extranodal disease, ECOG, IPI, immunosuppressive therapy and COO was identified between the 2 groups. The complete response (CR) rate for R-CHOP was 6/9 (66.6%) vs. 21/25 (84%) for R-EPOCH (p= 0.2701). Primary refractory disease was present in a third of the patients receiving R-CHOP vs. (4/25) 16% of the patients treated with R-EPOCH (p=0.2701). Treatment related mortality was low in both groups (1/9 (0.1%) vs 1/25 (0.04%) patients died during first line therapy with RCHOP vs REPOCH respectively). No difference was seen in terms of PFS and OS in the 2 groups. Median PFS and OS for RCHOP was 80.0 and 83.9 months respectively, the medians for R EPOCH were not reached (log-rank test p= 0.5430, 0.2855 for PFS and OS, respectively) (Figure 1C-1D). When the OS and PFS curves for RCHOP and REPOCH were analyzed based on COO, again no difference was noted. Conclusions : Non-GC subtype is more common than GC in monomorphic PTLD DLBCL. Clinical characteristics, EBV infection and time of onset post transplant is not different in the 2 subtypes. There is a trend suggesting better PFS and OS of PTLD DLBCL GC subtype, although not statistically significant, mirroring the outcome of GC vs non-GC COO in DLBCL of immunocompetent patients. With regard to therapy, R-EPOCH did not improve OS or PFS when compared to R-CHOP, but did not result in increased toxicity or treatment related mortality, which in our series was extraordinarily low for both therapies (&lt;=0.1%). Given the retrospective nature of our analysis, further studies of a larger cohort of patients is ongoing to validate these observations. Disclosures Sawas: Seattle Genetics, Gilead, Daiichi Sanko: Consultancy; Affimed: Research Funding. Lue:Kymera Therapeutics: Honoraria; Astex Pharmaceuticals: Honoraria. Marchi:Spectrum Pharmaceuticals, Verastem Oncology: Research Funding. Radeski:Corvus Pharmaceuticals: Research Funding. O'Connor:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Other: Travel Support, Research Funding; ADCT Therapeutics, Affimed, Agensys, Merck, Seattle Genetics, Spectrum, Trillium, and Verastem Oncology.: Research Funding.

Post-Transplant Cyclophosphamide in Allogeneic Bone Marrow Transplantation for the Treatment of Benign Hematologic Diseases

Post-transplant cyclophosphamide (PTCy) based GVHD prevention regimens are an emerging platform in allogeneic transplantation for hematological malignancies and are being prospectively compared to traditional standards. We present a single-center retrospective series of adult allogeneic bone marrow transplantation with the use of post-transplant cyclophosphamide in the setting of benign hematological conditions. Ten patients were treated between 2013 to 2019. Non-myeloablative conditioning consisted of rATG 0.5mg/kg on day (D) -9, 2mg/kg on D-7,-8 (ATG was in one patient with DBA), fludarabine 30mg/m2 daily from D-6 to D-2, cyclophosphamide 14.5mg/kg D-6 and D-5, and 200cGy of total body irradiation D-1. The bone marrow graft was administered on D0. GVHD prophylaxis consisted of post-transplant cyclophosphamide at 50mg/kg/day IV D+3, and +4 mycophenolate mofetil (MMF) at 15 mg/kg 3 times daily (maximum daily dose 3000 mg) starting on D+5 with taper beginning at D+35 to be off around D+100, and tacrolimus on D+5 with a target trough of 5-10 ng/mL with tapering beginning at D+180 with a goal to be off at D+360 in the absence of any GVHD. The median age at the time of transplantation was 42 (range 24-73) and 4 of 10 were female. Diagnoses include severe aplastic anemia (n=6), Diamond-Blackfan Anemia (n=2), paroxysmal nocturnal hemoglobinuria (n=1), and pure red cell aplasia (n=1). Median Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) was 0 (range 0-5). Bone marrow donors were haploidentical donors (n=6), fully matched unrelated donors(n=3), and fully matched sibling (n=1). The median donor age was 31 (range 22-53). Donor marrow grafts had a median CD34+ cell count of 4.41 x 106/kg recipient ideal body weight (range 1.12 x 106 to 20.5 x 106). At a median follow-up of 17 months (range 3, 63) after transplantation, all patients are alive, with donor-derived hematopoiesis and free of significant acute or chronic GVHD. Neutrophil and platelet engraftment occurred at a median of 21 (range 16-34) days and 33 (21-65) days, respectively, after transplantation. The patient with pure red cell aplasia developed secondary graft failure and required a second transplant using a peripherally collected graft with the same fully matched unrelated donor. For all recipients, median day +30 unsorted chimerism was 100% (range 71-100%). Patients have not experienced significant acute or chronic GVHD. There were no cases of grade II-IV acute GVHD observed. Chronic GVHD was observed in 3 patients with ocular disease (two mild, one moderate). All patients who are over 12 months after transplantation are off systemic immunosuppression. Three patients experienced CMV reactivation, two required preemptive treatment with oral valganciclovir, while the third had a single positive low level positive CMV PCR that resolved spontaneously. Three patients had low level positive EBV viremia, none of which required pre-emptive treatment. Other significant infectious complications before day +100 included BK cystitis in three patients, influenza, adenovirus cystitis, clostridium difficile colitis, streptococcal and enterococcal polymicrobial endocarditis, and enterococcal bacteremia. Significant non-infectious complications were rare. One patient experienced engraftment syndrome which resolved quickly with systemic steroid administration. Another patient suffered a small spontaneous subdural hemorrhage day +10 after transplantation, but subsequently made a full neurologic recovery. Post-transplant cyclophosphamide based non-myeloablative allogeneic bone marrow transplantation appears safe and effective for patients with non-malignant hematologic conditions and should be prospectively compared to historical regimens. Table 1. Cohort Characteristics. SAA - Severe aplastic anemia, DBA - Diamond Blackfan anemia, ATG- anti-thymocyte globulin, CSA- cyclosporine, Cy-cyclophosphamide, haplo- haploidentical Disclosures Defilipp: Incyte: Research Funding. Frigault:Nkarta: Consultancy; Novartis: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy; Juno/Celgene: Consultancy; Kite/Gilead: Honoraria; Incyte: Consultancy. Chen:Incyte: Consultancy; Magenta: Consultancy; Takeda: Consultancy; Kiadis: Consultancy; Abbvie: Consultancy.

2412 A Unique Case of Acute Liver Injury Due to Severe Epstein-Barr Virus Infection

INTRODUCTION: The liver is often affected by EBV infection, but involvement is commonly subclinical and self-limited. Infrequently, severe and potentially fatal EBV hepatitis has been reported in immunocompromised patients and, more rarely, in immunocompetent individuals. CASE DESCRIPTION/METHODS: A 25 y/o reasonably healthy man was transferred to a tertiary care hospital for advanced liver care due to increasing liver enzymes and concern for acute liver failure. Prior to presentation, he had experienced dry mouth, fatigue, and dark urine for six days. Of note, he worked in the police academy and regularly engaged in rigorous training. He used multiple OTC supplements, including clomiphene, creatine, ligandrol, and ibutamoren. Also, he would ingest 1600-2400 mg of ibuprofen in a day, for about 12 days per month, for general soreness from his workouts. Upon admission, his physical exam was notable for scleral icterus and generalized jaundice. He was A+Ox3 with no mental status changes. His labs were significant for AST 1,611, ALT 3,529, ALP 114, and total bilirubin 15.2 (direct 12.3). He had strongly positive EBV IgM titers, and was found to have a positive EBV PCR (52,000 copies/mL). During the admission, he had two episodes of seizure-like activity, the second of which was recorded on EEG without epileptiform activity. The episodes were attributed to syncope/presyncope in the setting of symptomatic anemia. He received a total of three units of packed RBCs due to anemia, but his hemoglobin did not initially improve. However, the last transfusion was warmed and there was adequate improvement in the hemoglobin, supporting a diagnosis of cold-agglutinin disease. Liver biopsy showed severe acute hepatitis, a mixed portal and lobular inflammatory infiltrate, and marked cholestasis. The overall picture was consistent with an EBV-driven hepatitis, along with a severe hemolytic anemia due to cold-agglutinin disease induced by EBV, in conjunction with likely predisposition to liver injury from taking various supplements. Ultimately, his liver enzymes improved and he was discharged in stable condition. DISCUSSION: EBV is associated with a variety of clinical manifestations and can present as cholestatic hepatitis with or without features of infectious mononucleosis (IM). Conversely, although rare in the immunocompetent, there is a need to test for EBV in cryptogenic hepatitis even if it remains difficult to prove its causative role. The mainstay of treatment for IM and other primary EBV diseases is supportive care.

EHRLICHIOSIS: A RARE CAUSE OF SEPSIS AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

SESSION TITLE: Case Report Semifinalists 1 SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of uncontrolled immune activation that can lead to multisystem organ failure. HLH is categorized as primary (familial) or secondary with triggers that include infections, malignancy, rheumatologic or metabolic conditions (1). Due to the high morbidity and mortality associated with HLH, early recognition and treatment are paramount. We describe a case of ehrlichiosis induced HLH and sepsis that did not respond to initial broad-spectrum antibiotics. CASE PRESENTATION: A 48 year old female with no significant past medical history presented to an outside hospital for persistent fevers up to 105°F and encephalopathy. Three weeks prior, she reported hiking in Kentucky and had noted multiple 1-2 mm erythematous papules that developed on her lower extremities. Ten days after she returned home, she developed fever, myalgias and malaise which prompted her to seek medical attention. Upon initial presentation, the patient appeared quite ill and the patient was started on broad spectrum antibiotics without improvement. Labs were notable for pancytopenia and a transaminitis. The patient was transferred to our facility on the fourth day of her hospital course. Upon arrival, doxycycline was initiated due to concerns for a tick-borne zoonosis and the patient rapidly improved within 48 hours of treatment. Given the constellation of symptoms evaluation for HLH was initiated and confirmed with a bone marrow biopsy significant for hemophagocytic histiocytes. The patient was continued on doxycycline and dexamethasone was initiated. An Erlichia chaffeensis PCR was obtained during the evaluation and was positive. The patient’s remaining infectious work-up was unremarkable with the exception of a positive qualitative EBV PCR. While EBV has been well described in its association to HLH, the robust improvement in the patient’s condition after initiation of doxycycline lends merit to ehrlichiosis as a cause for the patient’s HLH. The patient improved and was discharged home to complete a 14-day course of doxycycline. DISCUSSION: Ehrlichiosis is a rare cause of hemophagocytic lymphohistiocytosis with less than 15 adult cases reported in the literature (2-3). This is likely an underrecognized cause of HLH and the finding of HLH should prompt physicians to take a thorough travel and social history. As seen in our case, sepsis due to Ehrlichiosis does not respond to conventional antibiotics and thus initiation of doxycycline should be part of the antibiotic regimen if a tick-borne illness is suspected. CONCLUSIONS: Ehrlichiosis is an underrecognized cause of hemophagocytic lymphohistiocytosis. Reference #1: Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult patient. Blood 2015;125(19):2908-14. Reference #2: Naqash AR, Yogarajah M, Vallangeon BD, Hafiz M, Patel D, Kolychev E, Lebron DA, Liles D. Hemophagocytic lymphohistiocytosis (HLH) secondary to ehrlichia chaffeensis with bone marrow involvement. Ann Hematol. 2017;96(10):1755-1758. Reference #3: Wilfong EM, Hewlett JC, Kerchberger VE, Bloch KC, Sevin CM. Ehrlichia – an unusual cause of hemophagocytic lymphohistiocytosis. Am J Respir Crit Care Med 2018;197:A3386. DISCLOSURES: No relevant relationships by Erum Arain, source=Web Response No relevant relationships by Paul Chung, source=Web Response No relevant relationships by Emily Gilbert, source=Web Response

2007 Post Transplant Lymphoproliferative Disorder: A Rare Cause of Gastrointestinal Blood Loss Anemia

INTRODUCTION: Post transplant lymphoproliferative disorder (PTLD) is a rare complication after solid organ or stem cell transplant. Gastrointestinal tract is a common site of PTLD proliferation but PTLD related GI bleeding is rare. WE here by present a young Caucasian male on chronic immunosuppression for disease donor kidney transplant who presented with severe iron deficiency anemia related to GI blood loss from PTLD. CASE DESCRIPTION/METHODS: A 33-year-old Caucasian male with H/O Alport syndrome with ESRD S/P kidney transplant in 2012 on chronic immunosuppression with azathioprine and tacrolimus presented with 3 months of abdominal pain and intermittent melena. Hb was 5.4 g/dl, iron 7 mg/dl, ferritin 5 ng/ml. CT abdomen with dilated ileal loop with wall thickening and lobular contour. After resuscitation, patient underwent EGD and colonoscopy. EGD was unremarkable and colonoscopy revealed normal colon but nodular pattern in the terminal ileum (Figure 1). Multiple biopsies were taken. Histopathology and immunohistochemical staining were noted as florid follicular hyperplasia and rare EBV-positive cells, compatible with non-destructive PTLD (Figure 2) and positive CD 20 and high KI-67 proliferation index (Figure 3). Patients was discharged with reduction of his immunosuppressant therapy along with weekly rituximab. DISCUSSION: Gastrointestinal tract is the most common extranodal location of PTLD. EBV is a risk factor for PTLD and is associated with more than 80% of cases. Uncontrolled proliferation of EBV transformed B cells in the setting of compromised T cell mediated immunity due to immune suppression is involved in the pathogenesis if PTLD. Gastrointestinal manifestations may include obstruction, perforation and, very rarely, bleeding. Endoscopic manifestation include ulcers or nodular lesions with or without central ulceration and histologically lymphoid hyperplasia to lymphoma with nearly 80% positive EBV staining. Management is reduction of immune suppression; R-CHOP is an alternative in high risk patients. Early diagnosis and prompt treatment is cornerstone of PTLD gastrointestinal involvement.

EBV-Positive Primary Large B-cell Lymphoma: Highlighting the Role of XPO1 in the Diagnosis of Mediastinal Lymphomas

Abstract Background Primary mediastinal (thymic) large B-cell lymphoma (PMBL) is described to be almost always negative for EBV in the current WHO. In the context of a mediastinal lymphoma, the distinction between PMBL, classic Hodgkin lymphoma (CHL), diffuse large B-cell lymphoma, and mediastinal gray-zone lymphoma can be very difficult; hence, EBV positivity often aids in pointing away from a diagnosis of PMBL. However, since EBV positivity can occur in rare PMBLs, it should not be the deciding factor in the diagnosis; assistance from molecular studies is emerging in these difficult cases. Case Presentation We present a 19-year-old male patient with a 2-week history of cough, vocal changes, and occasional dysphagia who was found upon imaging to have a 6-cm mediastinal mass. The biopsy of this mass was morphologically consistent with PMBL but the tumor was EBV positive by in situ hybridization. Methods We performed next-generation sequencing using Oncomine Comprehensive Assay v3 (ThermoFisher Scientific) on formalin-fixed, paraffin-embedded tumor tissue with a buccal swab sample for germline control. Variant calling, filtering, and annotation were performed by the Yale Tumor Profiling Laboratory. Results We found somatic mutations in XPO1, SMARCB1, and MYC. Along with classic immunophenotype of PMBL including positivity for MAL, OCT2, BOB1, BCL6, CD79a, MUM1, CD20, and subset weak CD30, the diagnosis was confirmed to be PMBL. Conclusion This is the first EBV-positive PMBL in which molecular profiling was performed. XPO1, specifically the mutation hotspot (E571K), found in our case is involved in PMBL and CHL. This was clinically helpful in confirming the histopathologic diagnosis and also opening up a targeted therapeutic option. Selective inhibitors of nuclear export (SINEs) that block the binding of XPO1 to its cargo are in clinical development as antineoplastic agents and have shown promising activity against some hematologic malignancies.

111 Recurrent headaches with psychosis, CSF lymphocytosis, vessel beading and papilloedema- autoimmune/viral encephalitis with vasculopathy or unusual presentation of reversible cerebral vasoconstriction syndrome (RCVS)?

IntroductionHeadache is a common Neurology presentation in both outpatient and ED settings. We present a challenging headache in a previously asymptomatic young female patient.CaseA 27 year old female patient presented to ED with severe headache, vomiting and photophobia, after multiple presentations elsewhere, diagnosed as migraine, with normal neurological examination and MRI. Episodes of excruciating headache were associated with writhing and vomiting but spontaneously resolved with residual background pain. Indomethacin helped but she re-presented with headache and psychosis requiring intubation and ICU admission.Investigations included CSF - protein 0.85, leucocytosis 58 cells (lymphocytic) and normal cerebral venography. Acyclovir was commenced but viral PCRs were negative and she was extubated. MRI was suspicious for subtle posterior sulcal hyperintensity and beading in occipital and posterior cerebral arteries.Another episode occurred ten days later requiring intubation, examination showed papilloedema. CSF examination showed raised pressure, normal protein and 48 lymphocytes; flow cytometry and cytology were unrevealing. NMDA receptor antibody returned positive in serum but not CSF. Subtle beading in right PCA branches remained. IVIG and steroids were used with dramatic response. Further investigation revealed positive EBV serology only and papilloedema resolved. Steroids were weaned and she remains in remission.ConclusionWe present an interesting case of recurrent acute headaches with intracranial hypertension, psychosis and CSF lymphocytosis. The recurrent headaches and vessel beading suggest RCVS, perhaps triggered by viral or autoimmune encephalitis. The NMDA receptor antibody result should be interpreted with caution given the absence of antibody in CSF and dramatic recovery.

PF307 POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN LIVER AND KIDNEY TRANSPLANT RECIPIENTS OVER 33 YEARS: A SINGLE-CENTRE EXPERIENCE

Background: Post-transplantation lymphoproliferative disorders (PTLD) are a rare complication of transplantation, although with the increasing number of transplantations this paradigm is changing. Studies describe a peak in PTLD incidence in year 1 post-transplant, and some describe a second peak after 8–10 years. PTLD incidence beyond the 10th year is not well characterized.1 Early-onset of PTLD is frequently related with induction immunosuppression and is often characterized by EBV positivity. Late PTLD (more than 2 years after transplantation) is related with cumulative immunosuppression2. A large multicentre study revealed that 80 PTLD patients after solid organ transplant, whose the majority (80%) received rituximab-based treatment, had a 3-year overall survival (OS) of 62%.3 Aims: To review the prevalence of PTLD in a kidney and liver transplantation centre, time from transplant to diagnosis and outcome. Methods: Data were retrospectively collected from PTLD patients who underwent liver (LT) and kidney transplant (KT) at our centre between January 1985 and December 2018. KT patients received induction immunosuppression followed by maintenance with glucocorticoids, calcineurin inhibitors (CNI) and antimetabolite agent. LT patients received mainly maintenance monotherapy immunosuppression with CNI. As initial management of all patient with PTLD, immunosuppression was reduced, suspended or switched to mTOR inhibitors. The treatment was chosen according to the best practise at the time of diagnosis. Results: Among 2667 KT patients, 33 (1.2%) had PTLD, 22 were male, with a median age at transplantation of 37 years (range 14–64). Median time from transplant to PTLD diagnosis was 11.9 years (range 0.08–27.67), 29 patients (88%) had late PTLD and 17 (52%) were diagnosed ≥10 years from transplant. The overall OS at 3 years was 49%. Monomorphic PTLD was the most frequent diagnosis (25 patients, 75%): 16 had Diffuse Large B Cell Lymphoma (DLBCL), 3 had high grade lymphoma (HGL), not otherwise specified and the remaining 6 had other diagnosis. Nine of the 19 patients diagnosed with DLBCL/HGL were treated with Rituximab based chemotherapy (R-CT) and their 3-years OS was of 35%. Among 1211 LT patients 9 (0.7%) had PTLD, 7 were male, with a median age at transplantation of 50 years (range 21–60). Median time from transplant to PTLD diagnosis was 4.5 years (range 0.06–17.8). Six (67%) patients were diagnosed with late PTLD, 2 more than 10 years from transplant. Four had monomorphic PTLD, 3 DLBCL and 1 Burkitt Lymphoma, 2 patients were treated with R-CT and 2 with A-CT. The LT patients with PTLD had a 3 years OS of 40%. In respect to all 42 patients, with a median follow-up of 2.2 (range 0.01–20.5) years the OS at 3 years is 50%. Summary/Conclusion: We performed an analysis of the PTLD incidence in KT and LT patients in a single centre. Given the retrospective nature and the large period of data collection of this study, our incidence may be underestimated. We observed a higher incidence of PTLD in KT patients compared to LT, which is according to literature. Of those, more than half were diagnosed at least 10 years from transplantation, suggesting that maintenance immunosuppression might be the main reason for PTLD is this cohort. Patients diagnosed with DLBCL/HGL and treated with R-CT had a 3-years OS of 35%, representing a poorer outcome than what is described in literature3.

The Impact on Survival of EBV Positive Diffuse Large B- Cell Lymphoma, Not Otherwise Specified in Young Adults

Introduction: Epstein Barr virus-positive (EBV+) diffuse large B- cell lymphoma (DLBCL), not otherwise specified (NOS) is a new entity recognized by the WHO 2016. This entity was widely studied in older age patients, but in recent years there are few reports that show that EBV positive DLBCL, NOS can affect younger adults and there is a lack of evidence in this age group. The aim of this study is to evaluate the impact on survival in EBV+ DLBCL, NOS in young adults.Methods: The study was retrospective, reviewing clinical records of patients treated at Rebagliati Martins Hospital between years 2002 - 2013. Patients of both sexes ≥ 18 years old, but ≤ 50 years old, with the diagnosis of EBV+DLBCL, NOS were included. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists at our institution to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. Overall survival (OS) was determinate according to the Kaplan -Meier method, the comparison of the survival curves were made with the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted to evaluate hazard ratios (HR) for OS.Results: A total of 57 patients with a diagnosis of EBV+DLBCL, NOS were included in this analysis. The median age at diagnosis was 43 years (range 25-50 years), 61 % of patients were older than 40 years old and there was a slight female predominance (51%). Clinically, 55% presented ECOG >1, 57% had B symptoms, 68% had an extranodal disease as a primary tumor, 50% had stage III/IV and 26% had ≥ 1 extranodal site involved. EBV positivity was present in 16% of patients (9 patients). PDL-1 expression was present in 12% of patients. 92% received first-line treatment, but 7% of patients did not for progressive disease and death at diagnosis. During the treatment, 92% of patients received R-CHOP and 8% received other regimens. The overall response rate was 71%; 63% had a complete response and 7% had a partial response. The 5-year OS rate was 59%. In the univariate analysis, EBV positivity (<0.001) and ≥ 1 extranodal site involved (p=0.011) were associated with a poor prognosis. In the multivariate analysis, patients with EBV positive had a worse outcome (HR 7.8, 95% 2.2-25.9.2; p=0.001).Conclusions: The prevalence of EBV in young adults with DLBCL is high compared with other series and there is an adverse impact on overall survival in this group of patients. DisclosuresCastillo:Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

Addition of Rituximab to High-Dose Methotrexate Regimens Improves Complete Response Rates and Median Overall Survival in Non-Germinal Center Primary CNS Lymphoma

Background:Primary central nervous system lymphoma (PCNSL) is a rare type of extranodal non-Hodgkin lymphoma (NHL). Most cases occur in the immunocompetent population. Despite advances in therapy, the prognosis of PCNSL remains poor, with 5-year overall survival (OS) rates at 30-50% (Ferreri 2011). The standard of care treatment regimen includes high-dose methotrexate (HD-MTX), often in combination with other multiagent CNS penetrating chemotherapies. Although the addition of rituximab in systemic aggressive B-cell NHLs has shown improvement in OS, the benefit of this agent in PCNSL has not been confirmed in a prospective dataset (Bromberg 2017). The majority of PCNSLs are classified as diffuse large B-cell lymphomas (DLBCL), and the outcomes based on treatment and cell of origin (germinal center B-cell (GCB) vs. non-GCB subtype) have yet to be fully elucidated. In this review, we report our findings from a series of PCNSL patients based on treatment regimen and cell of origin.Methods:This is a retrospective study of patients with PCNSL diagnosed and treated at the University of Colorado Hospital from 1995 to 2017. Chart abstraction included demographics, DLBCL subtype by Hans algorithm (Hans 2004), treatment details, and outcomes. OS was examined using Kaplan Meier methods, while bootstrap resampling and a z-test was used to compare median survival times across strata. Fisher's exact test was used to determine whether treatment responses were different between those that received treatment withHD-MTX and rituximab versus HD-MTX without rituximab. A significance level of 0.05 was used for all tests. When assessing differences by subtype, treatment type, relapse, and treatment response the data was subset to include only patients without a prior HIV diagnosis.Results:71 patients with PCNSL were identified. 13 patients were HIV positive (the HIV status of 1 patient was unknown). Of the remaining 57 immunocompetent patients, 39 patients were treated with HD-MTX, of which 29 patients received rituximab in combination therapy. The most commonly received regimen was rituximab with methotrexate, procarbazine, and vincristine (R-MPV) (43.6%, 17 of 39). Median age in the HD-MTX subgroup was 65 years, with 83% of patients with KPS>70 at diagnosis. EBV positivity was noted in only 4 of 39 samples (10.2%), while 25 of 39 (64.1%) tested negative; the remaining patients' data was not available.Median OS was 29.9 months for all 71 patients (Figure 1). There was no significant difference in median OS between those with and without HIV (p=0.127).22 of 29 (75.9%) patients in the HD-MTX with rituximab group achieved a complete response (CR) while no patients (0%; 0 of 10) in the HD-MTX without rituximab group achieved a CR. The number of patients with a CR was significantly higher for those that received HD-MTX with rituximab compared to those that received HD-MTX without rituximab (p<0.001).Median OS for HIV negative patients treated with HD-MTX without rituximab (N = 10) was 32.6 months whereas median OS for HIV negative patients treated with HD-MTX with rituximab (N = 29) has not been reached at a median follow up of 33.4 months (range 1.5 - 116.9 months) (Figure 2)Subtyping was available for 23 patients without HIV treated with HD-MTX with or without additional agents. 6 patients had GCB subtype and 16 had non-GCB subtype. Median OS for GCB subtype has not yet been reached, while median OS for non-GCB subtype was 33.4 months (Figure 3). When analyzing data for patients who received HD-MTX and rituximab, median OS for GCB has not been reached, while median OS for non-GCB was 43.8 months (Figure 4).Conclusions:Our review of patients with PCNSL suggests that the addition of rituximab to a high dose MTX-based regimen improves survival although numbers are too small to determine any overarching statistical conclusion. CR rates were significantly higher in patients receiving rituximab in addition to HD-MTX compared to HD-MTX without rituximab. Patients with non-GCB subtype treated with HD-MTX and rituximab had increased median OS compared to median OS of non-GCB patients treated with HD-MTX without rituximab. However, in line with previous data we demonstrated worse outcomes associated with non-GCB subtype compared to GCB subtype. Future research is needed to focus on the characteristics of this subtype of PCNSL to improve outcomes with novel therapeutics. [Display omitted] DisclosuresKamdar:Genentech: Consultancy; Seattle Genetics: Speakers Bureau. Haverkos:Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

ATAXIA AS A PRESENTING SYMPTOM OF IMMUNE DYSREGULATION DISORDER IN THE SETTING OF EBV INFECTION

Introduction Epstein-Barr virus usually leads to mild, self-limiting infection in immunocompetent host. However, patients with defective cell-mediated cytotoxicity can get life-threatening infection with Hemophagocytic Lymphohistiocytosis features. Case Description 2-year-old Hispanic girl presented with acute onset of ataxia and slurry speech. No fever or lymphadenopathy were noted. CSF EBV PCR was positive and her MRI was consistent with viral encephalitis. She was treated with IVIG, steroids, and Acyclovir for 2 weeks. Over the next few months, her symptoms started to worsen again to the point that she could not sit up. Her MRI showed worsening of the inflammation with new hemorrhagic lesions. Brain biopsy was positive EBV DNA in situ hybridization and showed T cell and histiocytic infiltration. Her immunological evaluation revealed a mild reduction in T and NK cells number, normal B cells count, and normal immunoglobulin levels. HIV PCR was negative. SAP expression was normal; however, NK cell function was absent. HLH evaluation was unremarkable except for elevated serum and CSF neopterin levels. She was treated with steroid in addition to rituximab (IV and then intrathecally) to decrease the EBV viral load (fig1). Few weeks later, the Genetic test revealed a missense homozygotic mutation of perforin gene (c.1337A>C) which is validated by flow cytometry. With a diagnosis of primary HLH confirmed, the patient was treated with etoposide waiting for matched donor bone marrow transplant. Discussion NK cells disorders should be considered in pediatric patients with severe or unusual EBV infection. Rituximab is effective in decreasing EBV viral load.

The fasting blood glucose and long non-coding RNA SNHG8 predict poor prognosis in patients with gastric carcinoma after radical gastrectomy.

This prospective study sought to evaluate the prediction of fasting blood glucose and long non-coding RNA (lncRNA) SNHG8 for the risk of gastric carcinoma mortality. A total of 217 gastric carcinoma patients underwent radical gastrectomy were included during 2012-16. The final follow-up was finished in January 2017. The aggregate hazard ratio(HR) demonstrated that poor prognosis of gastric carcinoma was associated with fasting blood glucose (HR= 1.29, P=0.037), SNHG8 expression(HR = 1.10, P= 0.009), positive distant metastasis(HR = 2.99, P= 0.020), EBV positive (HR = 3.40, P=0.002), and tumor size more than 5.0 cm (HR = 3.36, P= 0.005). In survival analysis, elevated fasting blood glucose (P =0.007) and high SNHG8 expression (P =0.007) were significantly associated with shorter survival times in gastric cancer. Significant multiplicative interaction was shown between fasting blood glucose and SNHG8 expression (chi-squared=7.81, Pmultiplicative =0.005), without statistical additive interaction. Fasting blood glucose and SNHG8 expression could predict poor prognosis after radical gastrectomy. LncRNA SNHG8 could be applied as a novel epigenetic molecular target in gastric carcinoma.

A Very Rare Complication of Hepatitis a Infection: Acute Myocarditis

Hepatitis A is a common viral infection with a benign course but in rare cases can progress to acute liver failure. A rare manifestation of hepatitis A is acute myocarditis. We report a case of a 30-year-old female, without significant past medical history who presented with four days of fatigue, myalgias, nausea, non-bloody, non-bilious emesis and non-bloody diarrhea along with anorexia. Physical exam was significant for mild scleral icterus and right upper quadrant abdominal tenderness, without peritoneal signs or fluid wave. She had intact mentation, no asterixis or stigmata of liver disease. Lab work revealed severe elevations in liver transaminases, AST = 6,769U/L, ALT = 8.479U/L., INR = 2.0 and acute viral hepatitis panel was positive for hepatitis A IgM only. EBV IgG and IgM were positive but heterophile assay and EBV PCR was negative (Figure 1 and 2). Abdominal US revealed homogenous hepatic echotexture without evidence of focal hepatic lesions. There was mild intrahepatic biliary ductal dilatation with common bile duct measuring 2mm. On her 3rd day of admission the patient developed chest pain and nonspecific ECG changes. Her troponin rose to 16.4 ng/mL, and an echocardiogram revealed global hypokinesis and a depressed ejection fraction (EF) at 30%. A coronary CT angiography showed no evidence of significant coronary artery disease. The patient was managed supportively and symptoms and laboratory findings slowly improved over the next 7 days. Her chest pain resolved and follow up echocardiogram showed improved EF to 45%. To our knowledge, there are 3 case reports of myocarditis associated with hepatitis A (Figure 3). Like previous case reports, a presumptive diagnosis of myocarditis secondary to hepatitis A was made, despite endomyocardial biopsy (EMB) being the gold standard for definitive diagnosis. However, EMB is not always indicated especially if it would not change management. Despite improving liver indices, the patient developed myocarditis. Therefore, it may be worthwhile to monitor patients for cardiac abnormalities despite signs of improving transaminases. Comparison of these case reports also highlights that higher elevations in transaminases may be associated with more severe cardiomyopathy. However, given the rarity of this manifestation, true associations are yet to be elucidated. The purpose of this case report is to increase awareness of this disease entity, so it can be recognized and considered in clinical practice.2305_A Figure 1. Key laboratory values on admission.2305_B Figure 2. Trend of liver function tests and troponin obtained during hospital course. Day 1 is day of admission. Day 17 is outpatient follow up.2305_C Figure 3. Other reported cases of myocarditis in hepatitis A.

Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer.

Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.

Pediatric renal transplantation: A retrospective single-center study on epidemiology and morbidity due to EBV.

Pediatric R-Tx patients are at high risk of developing EBV primary infection. Although high DNA replication is a risk factor for PTLD, some patients develop PTLD with low viral load. In this retrospective single-center study including all pediatric patients having received R-Tx (2003-2012 period), we aimed to identify risk factors for uncontrolled reactions to EBV (defined as the presence of a viral load >10000copies/mL or PTLD). A Cox proportional hazard model was performed. A total of 117 patients underwent R-Tx at a mean age of 9.7±5.3years, 46 of them being seronegative for EBV at the time of R-Tx. During follow-up, 54 patients displayed positive EBV viral load, 22 of whom presenting with primary infection. An uncontrolled reaction to EBV was observed in 24 patients, whilst 4 patients developed PTLD. Univariate and multivariate analyses suggested the following risk factors for an uncontrolled reaction: age below 5years, graft from a deceased donor, ≥5 HLA mismatches, EBV-seronegative status at the time of R-Tx, and a secondary post-Tx loss of anti-EBNA. Monitoring anti-EBNA after R-Tx may contribute to the early identification of patients at risk for uncontrolled reaction.

Human immunodeficiency virus-related Epstein-Barr virus-associated smooth muscle tumours: South African experience from Chris Hani Baragwanath Academic Hospital

Background: Despite the rampant human immunodeficiency (HIV) epidemic in Africa, there is a paucity of published data of HIV-related Epstein-Barr virus-associated smooth muscle tumours (EBV-SMT) from Africa.Methods: We embarked on retrospective documentation of the clinicopathological features of confirmed HIV-related EBV-SMT over a 5-year time frame at the largest hospital in Africa. All haematoxylin and eosin stained tissue sections, immunohistochemistry and EBV in situ hybridisation (ISH) investigations were reviewed in conjunction with clinical data.Results: Fourteen (n = 14) EBV-SMT were confirmed in 13 patients (age range: 10–53 years). Five paediatric patients and a predominance of females (70%) were evident in this series. All patients were HIV seropositive and CD4 counts ranged from 1 to 1331 cells/ul (median 355 cells/ul; mean 442 cells/ul). Tumour-associated pain was a common symptom in the paediatric age group, while neurological symptoms were frequent in the adults due to paraspinal cervicothoracic involvement. Unusual topography, multifocality (n = 5) and smooth muscle morphology in association with round cell features (n = 3) were evident. Immunoexpression of desmin (n = 12), SMA (n = 12) and h-Caldesmon (n = 8) were consistent findings and positive EBV ISH nuclear signaling was demonstrated within all of these tumours. Treatment included antiretroviral therapy, surgical resection, radiation and/or palliative therapy.Conclusion: HIV-associated EBV-SMT are rare tumours that may develop in paediatric or adult patients. A female predominance and multifocal topographic involvement may be evident. AIDS-related co-morbidities are likely to contribute to mortality; and, when these tumours occur in paraspinal regions, debilitating neurological morbidity may manifest.