scholarly journals 1393. Tuberculosis (TB) After Solid-organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S506-S506
Author(s):  
Cecilia F Peña-Puga ◽  
Oscar Morado-Aramburo ◽  
Darwin Lambraño-Castillo ◽  
Jennifer Cuellar-Rodríguez
Keyword(s):  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
First Year ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Latent Tb ◽  
Disseminated Disease

Abstract Background Tuberculosis is an important opportunistic infection that affects transplant recipients; the risk of active infection increases significantly when compared with the general population. Most disease results from reactivation of latent infection, being extrapulmonary and disseminated disease the most common presentations. Most cases occur during the first year post-transplantation when immunosuppression is higher. We describe the clinical characteristics of patients diagnosed with TB after transplant. Methods Single-center, retrospective study of adult SOT and HSCT recipients in Mexico City, who developed active TB after transplant. We reviewed medical records, and collected demographic data, clinical characteristics, and outcome. Results We identified 16 patients with post-transplant TB; 13 SOT, and 3 HSCT recipients. The majority of SOT recipients were women (53.8%); median age was 43 years, 9 were kidney and 4 liver transplant recipients. At TB diagnosis, 84.6% of patients were on 3 immunosuppressors. Latent TB was assessed before transplant in 5 patients (38.4%), of these 3 (60%) were tuberculin skin test+, and 2 received isoniazid. Extrapulmonary disease was most common (7, 53.8%). Predominant symptoms were fever (53.8%), chills (30.8%), and diaphoresis (38.5%); six were diagnosed during the 1st year (46.2%) post-transplant; the median of time to diagnosis was 24 months after transplant. The diagnosis was made by histopathology in most cases. Twelve patients received first-line anti-TB treatment. Overall mortality was 30.8%, directly attributable to TB in 2. In the HSCT group, 2 were women; median age was 22 years, 2 allogeneic and 1 autologous transplant. One patient had been treated for latent TB before transplantation. Two developed disseminated disease. Two patients presented within 6 months after the transplant, and the other within a year. Mortality was 100%, attributable to the infection in two patients. Conclusion In regions with intermediate to a high prevalence of TB; post-transplant TB could result from reactivation or post-transplant exposure. Most cases occur within the first year post-transplant; clinical symptoms are nonspecific, which lead to a delay in diagnosis. Morbidity and mortality remains high. Disclosures All authors: No reported disclosures.

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

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19543-e19543
Author(s):  
Hira Ghazal Shaikh ◽  
Rafiullah Khan ◽  
Michael Grabel ◽  
Roman Jandarov ◽  
Mahmoud Charif ◽  
...  
Keyword(s):  
Poisson Regression ◽  
Lymphoproliferative Disorder ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Solid Organ ◽  
Cell Transplant ◽  
Annual Income ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Post Transplant

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%), < 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 > $63000 (versus < $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.

scholarly journals Clinicopathologic Features of Tissue Granulomas in Transplant Recipients: A Single Center Study in a Nontuberculosis Endemic Region

2020 ◽  
Author(s):  
Eliezer Zachary Nussbaum ◽  
Kishan K. Patel ◽  
Roland Assi ◽  
Rita Abi Raad ◽  
Maricar Malinis ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Solid Organ ◽  
Cell Transplant ◽  
Clinicopathologic Features ◽  
Transplant Recipients ◽  
Endemic Region ◽  
Hematopoietic Stem ◽  
Cryptogenic Organizing Pneumonia ◽  
Symptomatic Disease ◽  
Asymptomatic Patients

Context.— There is a paucity of literature about tissue granulomas in transplant patients. Objective.— To characterize the clinicopathologic features of granulomas in this population and develop a clinically judicious approach to their evaluation. Design.— We performed chart reviews of solid organ and allogeneic hematopoietic stem cell transplant recipients at Yale New Haven Hospital to identify patients with granulomas on biopsy obtained pathologic specimens. Pretransplant and posttransplant specimens were included. Data points included demographics, clinical presentation, epidemiologic risk factors, biopsy indication, location and timing, immunosuppression, histopathology, microbiology, and associated clinical diagnosis. Granuloma-related readmissions and mortality were recorded at 1, 3, and 12 months. Results.— Biopsy proven granulomas were identified in 56 of 2139 (2.6%) patients. Of 56, 16 (29%) were infectious. Common infectious etiologies were bartonellosis (n = 3) and cytomegalovirus hepatitis (n = 3). Tuberculosis was not identified. Clinical symptoms prompted tissue biopsy in 27 of 56 (48.2%) cases while biopsies were obtained for evaluation of incidental findings or routine disease surveillance in 29 of 56 (51.8%). Presence of symptoms was significantly associated with infectious etiologies; 11 of 27 (40.7%) symptomatic patients compared with 5 of 29 (17.2%) asymptomatic patients had infectious causes. One death from granulomatous cryptogenic organizing pneumonia occurred. In pretransplant asymptomatic patients, no episodes of symptomatic disease occurred posttransplantation. Conclusions.— Granulomas were uncommon in a large transplant population; most were noninfectious but presence of symptoms was associated with infectious etiologies. Granulomas discovered pretransplant without clear infectious etiology likely do not require prolonged surveillance after transplantation. Symptomatology and epidemiologic risks factors should guide extent of microbiologic evaluation.

scholarly journals Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients

2020 ◽  
Vol 33 (4) ◽  
Author(s):  
Marie-Céline Zanella ◽  
Samuel Cordey ◽  
Laurent Kaiser
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Clinical Significance ◽  
Viral Infections ◽  
Solid Organ Transplantation ◽  
High Morbidity ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem

SUMMARY Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians’ radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.

scholarly journals 2571. Norovirus Infection and Gut Microbiota in Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S893-S893
Author(s):  
Pearlie P Chong ◽  
Pearlie P Chong ◽  
Sarah K Hussain ◽  
Nicole Poulides ◽  
Laura Coughlin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
16S Rrna Gene Sequencing ◽  
Antibiotic Use ◽  
Rrna Gene ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem

Abstract Background In vitro studies have shown that enteric viruses require the gut microbiota (specific members of the Enterobacteriaceae family) for efficient infection of the gastrointestinal tract. Human norovirus (NV) infection in transplant recipients may be chronic and severe. The role of gut microbiota has not been defined in this setting. We hypothesized that gut microbiota diversity and composition are different in norovirus-infected transplant patients. Methods We performed a single-center, pilot, prospective cohort study of adult solid-organ transplant and hematopoietic stem cell transplant recipients with diarrhea. Serial fecal samples were collected and processed for gDNA. Norovirus levels were quantified by PCR and gut microbiota profiling determined by 16S rRNA gene sequencing. Results Twenty-five transplant recipients were included: 9 with NV infection and 16 without. Age (61 ± SEM 2.3 years vs. 54 ± 3.5 years; P = 0.172), duration of diarrhea prior to diagnosis (105 ± 43 days vs. 20 ± 7 days; P = 0.146), prior cumulative antibiotic use (42 ± 12 days vs. 46 ± 17 days; P = 0.646), anti-anaerobic antibiotic use (7 ± 3 days vs. 11 ± 6 days; P = 0.643) and length of hospitalization (12 ± 6 days vs. 12 ± 3 days; P = 0.624) were not different between transplant recipients with and without NV infection. Interestingly, the relative abundance of Enterobactericeae was significantly higher in NV-infected transplant recipients compared with those without NV infection (26 ± 5.8% vs. 6.2 ± 2.8%; P = 0.017, Mann–Whitney) (Figure 1). In contrast, the abundance of the Phyla Bacteroidetes (11.2 ± 5.2% vs. 26.3 ± 6.5%; P = 0.191), and Firmicutes (26.8 ± 7.6% vs. 24.9 ± 4.7%; P = 0.803), were not significantly different between those who were NV and not NV-infected. Of note, the diversity metrics of Shannon (3.5 ± 0.4 vs. 3.8 ± 0.3; P = 0.637) and inverse Simpson indices (1.3 ± 0.1 vs. 1.1±0.1; P = 0.419) were not significantly different between the two groups. Conclusion Norovirus-infected transplant recipients had a significantly higher relative abundance of Enterobactericeae in their gut microbiota compared with transplant recipients without norovirus infection. Future studies are needed to explore if this association is mechanistically important for norovirus infection. Disclosures All authors: No reported disclosures.

Generation of Epstein Barr Virus Specific Cytotoxic T Lymphocytes (EBVCTLs) Resistant to the Immunosuppressive Drug Tacrolimus (FK506)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3536-3536
Author(s):  
Biagio De Angelis ◽  
Gianpietro Dotti ◽  
Concetta Quintarelli ◽  
Leslie E Huye ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Immunosuppressive Agents ◽  
Retroviral Vector ◽  
Immunosuppressive Drugs ◽  
Thymidine Uptake ◽  
Solid Organ ◽  
Cell Transplant ◽  
Antigen Specificity ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Adoptive transfer of autologous EBV-CTLs to hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients is a safe and often effective means for prevention and treatment of EBV-associated post transplant lymphoproliferative disorders (PTLD). Although immunosuppressive drugs can be tapered in patients developing PTLD, they often cannot be completely withdrawn because of the risk of graft rejection, a particular concern in lung, heart or liver transplant recipients. These immunosuppressive drugs may limit the expansion, persistence and efficacy of transferred EBV-CTLs. One of the most widely used immunosuppressive agents is FK506 whose effects are highly dependent on binding FKBP12 proteins, since T cells generated from FKBP12 knockout mice are completely resistant to the inhibitory effects of FK506. We have generated EBV-CTLs resistant to FK506 by knocking down FKBP12 using a small interfering RNA (siRNA) stably expressed from a retroviral vector. After extensively screening potential target sequences, we identified one, designed as siRNA4, that knocks down >90% of FKBP12 protein expression in T cell lines and also in EBV-CTLs, as assessed by Western blotting. We then generated two retroviral vector encoding for siRNA4/eGFP and irrelevant siRNA/eGFP, respectively. These vectors were used to transduce established EBV-CTL lines generated from 7 EBV-seropositive donors. Transduction efficiency was 46.3±22.5% and 55.4±27.5% for siRNA4 and irrelevant-siRNA, respectively. We measured the proliferation of transduced CTLs in the presence of FK506, in short term and long term cultures. Using a thymidine uptake assay, we found that the inhibiton of proliferation by increasing concentrations of FK506 was significantly diminished in siRNA4+ CTLs compared to control CTLs (41±4% inhibition for siRNA4+ CTLs vs 74± 2% for control CTLs). To evaluate the effects of knocking down FKBP12 in long-term cultures, control and siRNA4+ CTLs were stimulated weekly with the antigen (autologous EBV-LCL) with or without the addition of FK506 (5ng/ml) and low dose IL-2 (20U/mL). We found that the proportion of siRNA4+ CTLs increased over time not only as a percentage of GFP+ cells (from 46±22% to 89.4±5.3% after 5 stimulations) but also numerically (median fold expansion: 34.3, range 5–60). In contrast, control EBV-CTLs did not show any selection in culture, since the percentage of GFP+ cells remained unchanged (from 56±27% to 57±23.1%) and CTLs ceased to proliferate (median fold expansion: 2, range 0–5). Finally, we found that siRNA4+ CTLs retained their antigen specificity, having MHC-restricted cytotoxic activity against EBV-targets (66±22% vs 16±12% for autologous and allogenic LCL, respectively at an E:T ratio of 20:1 for siRNA4+ CTLs; 61±12% vs 15±12% for autologous and allogenic LCL, respectively, for control CTLs). Modified CTLs also maintained their production of IFNγ in response to specific EBV-peptides, as assessed by ELIspot assays. We are currently evaluating the in vivo expansion of genetically modified EBV-CTLs in the presence of FK506. In conclusion, we have developed a strategy that produces EBV-CTLs resistant to FK506. This strategy may be beneficial to improve EBV immune reconstitution in patients at high risk of developing post transplant lymphoma.

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