Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients

Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to maintain the drug’s efficacy and reduce the consequences of overexposure. Tacrolimus is characterized by substantial intra- and inter-individual pharmacokinetic variability. At steady state, the tacrolimus blood concentration to daily dose ratio (C/D ratio) has been described as a surrogate for the estimation of the individual metabolism rate, where a low C/D ratio reflects a higher rate of metabolism. Fast tacrolimus metabolism (low C/D ratio) is associated with the risk of poor outcomes after transplantation, including reduced allograft function and survival, higher allograft rejection, CNI nephrotoxicity, a faster decline in kidney function, reduced death-censored graft survival (DCGS), post-transplant lymphoproliferative disorders, dyslipidemia, hypertension, and cardiovascular events. In this article, we discuss the potential role of the C/D ratio in a noninvasive monitoring strategy for identifying patients at risk for potential adverse events post-transplant.

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Severe Hemolysis Due to Passenger Lymphocyte Syndrome in Three Recipients of Organs from a Donor with Multiple Red Cell Alloantibodies.

Blood ◽

10.1182/blood.v110.11.4023.4023 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4023-4023

Author(s):

Jake Shortt ◽

Mark N. Polizzotto ◽

David Roxby ◽

Geoff Magrin ◽

Andrew Webb ◽

...

Keyword(s):

Blood Group ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ ◽

Red Cell ◽

Post Transplant ◽

Antibody Screen ◽

Group B ◽

The Right ◽

Positive Direct

Abstract Passenger lymphocyte syndrome (PLS) is rare following solid organ transplantation. We describe 3 transplant recipients who developed severe hemolysis after receiving organs from a single donor with multiple red cell (RC) alloantibodies. The donor was a 54 y.o. male, blood group O Rh(D) negative (rr) with a positive antibody screen due to anti-D, anti-C and anti-k. His Cellano negative and RC alloantibody status was well characterized antemortem, given that he was a rare RC phenotype donor for the Australian Red Cross Blood Service (ARCBS). The lungs and the liver were offered for organ donation. The right single lung recipient was a 61 y.o. male with emphysema (blood group O Rh(D) positive [R2r]). From post transplant day (PTD) 0 to 10 his hemoglobin (Hb) fell from 126g/L to 69g/L without bleeding and with elevated hemolytic markers. A positive direct antiglobulin test (DAT) due to IgG was noted and anti-D eluted. Management included increased immunosuppression and transfusion of 2 RC units (rr, k positive). Ongoing hemolysis required a second transfusion at PTD 24. To facilitate tapering of corticosteroids, intravenous immunoglobulin (IVIG; 2g/kg in divided doses) was administered. The patient subsequently stabilized and 3 months post-transplant has mild compensated hemolysis with persisting anti-D. The left single lung recipient was a 59 y.o. female with emphysema (blood group O Rh(D) positive [R1r]). From PTD 0 to 10, Hb fell from 91g/L to 73g/L with elevated hemolytic markers. The antibody screen and elution demonstrated anti-D, and she was transfused with 2 RC units (rr, k positive). Three months post transplant she has ongoing evidence of mild compensated hemolysis with persisting anti-D. The liver recipient was a 45 y.o. male with Hepatitis B (blood group B Rh(D) positive [R1R1]). From PTD 0 to 13 Hb fell from 102g/L to 64g/L without bleeding. The DAT was positive (IgG) at day 4. Anti-D+B+C were detected in the plasma and anti-C+D+k+B were found in eluates. He was managed with increased immunosuppression and transfusion of 2 RC units (rr, k negative). Fresh Cellano negative units were accessed through the ARCBS rare RC register. The patient has subsequently also stabilized, despite ongoing seropositivity for anti-D (but not anti-k). These cases highlight the potential for severe hemolysis due to PLS following solid organ transplant. This is the first apparent description of PLS where anti-k has been implicated, with significant hemolysis in all recipients of organs from the same donor. We conclude that the identification of donor RC alloantibodies at the time of transplant should prompt close surveillance for development of PLS. Consideration of strategies to ameliorate hemolysis, such as early use of IVIG, is suggested. Where an antibody to a high incidence antigen (such as Cellano) is detected, early notification of central blood bank services may facilitate call up of phenotyped donors and provision of rare units.

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A Single-Center Retrospective Study of 140 Patients with Post-Transplant Lymphoproliferative Disorder Following Solid Organ Transplantation

Blood ◽

10.1182/blood.v128.22.4227.4227 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4227-4227

Author(s):

Michael D Jain ◽

Ryan Lam ◽

Rashmi S Goswami ◽

Krystyna Tybinkowski ◽

Parneet K Cheema ◽

...

Keyword(s):

Organ Transplantation ◽

Competing Risks ◽

Research Funding ◽

Lymphoproliferative Disorder ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ ◽

Early Relapse ◽

Transplant Program ◽

Poor Outcomes

Abstract Background: Post-transplant lymphoproliferative disorder (PTLD) is an uncommon, heterogeneous disease that occurs in the setting of immune suppression following solid organ transplantation. As the transplant population ages over time, the spectrum of PTLD histologies and their treatment has evolved; we report here our recent experience with PTLD from a large multi-organ transplant program. Methods: We identified patients from the Multi-Organ Transplant Program at University Health Network (UHN) who were diagnosed with PTLD between January 1, 2000 and December 31, 2015. We describe the characteristics and outcomes of this cohort, with a focus on the outcome of patients with the diffuse large B cell (DLBCL) subtype of PTLD treated in the rituximab era. Results: A total of 140 patients were diagnosed with PTLD at UHN during this time period (Table 1): 38% were female and median age at time of diagnosis was 50 (interquartile range, IQR Q1/Q3, 37 to 62 years). The most commonly implicated transplants were liver and kidney (33% and 32%), as well as lung (20%) and heart (7%). The median time from organ transplantation to PTLD diagnosis was 61 months (IQR 9 to 136), with 70% of cases occurring more than 12 months following solid organ transplant. Pathologically, the majority of the patients had monomorphic PTLD, with DLBCL (n = 86) being most common. Where classifiable by the Hans algorithm (n = 68), the majority of the DLBCL types were of the non-germinal center B cell type (non-GCB, 76.5%). Of 24 DLBCL patients with available FISH, 7 had a MYC translocation (29%). Treatment and outcome varied by PTLD subtype (Table 2). For the overall cohort (n = 140), the median OS was 5.1 years. Highlighting competing risks, less than half of patients died of PTLD, with the remainder of mortality due to complications of solid organ transplantation, or less commonly, due to treatment-related mortality. Polymorphic PTLD (n = 17) was treated in a variety of ways ranging from reduction in immunosuppression (RIS) alone to R-CHOP; median OS was 10.3 years. Less common histologic subtypes (Hodgkin, Burkitt, T cell) were treated with therapies specific to those lymphomas. For DLBCL (n = 86), treatment consisted of RIS alone (10.5%; OS 4.4 years) or RIS followed by local treatment (involved field radiation or surgical resection) (7.0%; OS not reached); single agent rituximab (R) (22.1%; OS not reached); sequential R followed by CHOP (11.6%; OS 1.5 years), or upfront R-CHOP (43.0%; OS 3.4 years). Median OS for patients classified as non-GCB was not worse than those classified as GCB (OS 6.2 vs. 4.7 years, p = 0.93). In the DLBCL cohort, 20 patients had progression during or after first line therapy, with 14 patients receiving additional treatment. Patients with early relapse during initial therapy or within the first 3 months (n = 13) did poorly compared to patients with later relapse occurring after 3 months (n = 7; median OS 0.7 vs 5.6 years, p < 0.01). This was similar to the entire cohort, where 40 patients relapsed and early relapsed/refractory patients also had poor outcomes compared to late relapsing patients (median OS 0.8 vs. 5.1 years, p <0.01). Six patients in the overall cohort had an autologous stem cell transplant for progressive disease; 4 remain in remission after 5 years (range, 1.3 to 5.8 years follow-up). Conclusion: In this recent retrospective cohort, PTLD was generally late onset and the median OS of all patients was 5 years. The most common histology was DLBCL (non-GCB subtype), but cell of origin did not influence outcome. Patients with early relapse or refractory disease had poor overall survival. Due to competing risks and comorbidities, many PTLD patients continue to have poor outcomes despite modern treatment strategies. Disclosures Jain: Roche Canada: Research Funding. Prica:Janssen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria. Kuruvilla:Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Honoraria; Roche Canada: Consultancy, Honoraria, Research Funding; Merck: Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria.

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EBV-negative post-transplant lymphoproliferative disorder: Clinical characteristics, response to therapy, and survival.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8578 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8578-8578

Author(s):

Daniel S. Heil ◽

Marlise Rachael Luskin ◽

Edward Allen Stadtmauer ◽

Stephen J. Schuster ◽

Donald Edward Tsai ◽

...

Keyword(s):

Lymphoproliferative Disorder ◽

Survival Rates ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Response Rates ◽

Response To Therapy ◽

Solid Organ ◽

Post Transplant ◽

Barr Virus ◽

Epstein Barr

8578 Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. PTLD is frequently linked with Epstein-Barr virus (EBV) and it was suggested that EBV negativity is associated with a poor prognosis and lack of response to reduction of immunosuppression (RI). We conducted a case-control study to identify the characteristics, outcome and response to therapy of EBVpos and EBVneg PTLD over a 20-year period. Methods: We reviewed data on patients diagnosed with PTLD at U. Penn. between 1982 and 2012. We determined EBV positivity on tumor samples according to WHO criteria. We compared clinical and pathologic characteristics, response to therapy, and survival of EBVpos and EBVneg patients. Results: Of 222 patients diagnosed with PTLD, we verified the EBV status of 169 patients, of whom 35% were EBVneg and 65% were EBVpos. Mean follow-up was 46.7 months. Median time from transplant to PTLD was 23.1 mo. in EBVpos vs. 59.3 mo. in EBVneg (p=0.003) with 42% of EBVpos patients being diagnosed within the first year after transplant vs. 15% in the EBVneg group (p<0.001). EBVneg PTLD was more likely to occur in non-thoracic vs. thoracic transplants (p=0.006). 28% of patients with EBVpos PTLD presented with disease originating from the graft vs. 14% in the EBVneg group (p=0.03). In terms of histology, 36% of EBVpos patients had polymorphic PTLD vs. 7% of EBVneg patients (p<0.001). Of patients who were treated with RI alone (40% of patients in both groups), the overall response rates were 50% and 48% in EBVpos and EBVneg patients respectively (p=NS). Response rates to rituximab were also similar. There was no difference in the mortality risk between groups (HR=1.04; p=0.84). The 5-year survival rates were 47% and 51% in EBVpos and EBVneg PTLD respectively (p=NS). Conclusions: In a large single-center series, EBVneg PTLD was associated with late occurrence after transplant, monomorphic histology and similar outcome in comparison with EBVpos PTLD. Importantly, the response of EBVneg PTLD to RI and rituximab was no different than EBVpos PTLD. These results have implications for the management of solid organ transplant recipients with PTLD.

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Torque teno viral load reflects immunosuppression in paediatric kidney-transplanted patients—a pilot study

Pediatric Nephrology ◽

10.1007/s00467-020-04606-3 ◽

2020 ◽

Vol 36 (1) ◽

pp. 153-162 ◽

Cited By ~ 3

Author(s):

Phoebe Uhl ◽

Andreas Heilos ◽

Gregor Bond ◽

Elias Meyer ◽

Michael Böhm ◽

...

Keyword(s):

Viral Load ◽

Graft Function ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Kidney Graft ◽

Post Transplant ◽

The Individual ◽

Almost All ◽

Plasma Load

Abstract Background Chronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation. Methods TTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally. Results TTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor–based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found. Conclusions TTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections—common consequences of insufficient or too intense IS.

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Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

Current Pharmaceutical Design ◽

10.2174/1381612826666200531152901 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3497-3506

Author(s):

Raymund R. Razonable

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Cmv Infection ◽

Future Directions ◽

Prevention And Treatment ◽

Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

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#74: Development of a Solid-Organ Transplant-Specific Antibiogram in a Tertiary Pediatric Hospital in Canada

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa170.001 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

pp. S1-S1

Author(s):

T Kitano ◽

M Science ◽

N Nalli ◽

K Timberlake ◽

U Allen ◽

...

Keyword(s):

Treatment Guidelines ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Lower Sensitivity ◽

Solid Organ ◽

Pediatric Hospital ◽

Post Transplant ◽

Significant Difference ◽

Organ Specific ◽

Wide Population

Abstract Background Solid-organ transplant (SOT) patients are more vulnerable to infections by antimicrobial-resistant organisms (AROs) because of their hospital exposure, compromised immune systems, and antimicrobial exposure. Therefore, it may be useful for transplant facilities to create transplant-specific antibiograms to direct empirical antimicrobial regimens and monitor trends in antimicrobial resistance. Methods SOT (i.e., lung, liver, renal, and heart) antibiograms were created using antimicrobial susceptibility data on isolates from 2012 to 2018 at The Hospital for Sick Children, a tertiary pediatric hospital and transplant center in Toronto, Ontario. The Clinical Laboratory Standards Institute (CLSI) guidelines were followed to generate the antibiograms. The first clinical isolate of a species from a patient in each year was included irrespective of body site; duplicates were eliminated and surveillance cultures were excluded. Results from 2 years of data were pooled on a rolling basis to achieve an adequate sample size in both SOT and hospital-wide antibiogram. The SOT antibiogram was then compared with the hospital-wide antibiogram of the compatible 2 pooled years from 2012 to 2018. For subgroup analyses in the SOT population, organ-specific antibiograms and transplant timing-specific antibiograms (pretransplant, post-transplant <1 year, and post-transplant ≥1 year) between transplant and sample collection dates were analyzed. All proportions were compared using the χ 2 test. Results The top 5 organisms in one (2 year) analysis period of the SOT antibiogram were Escherichia coli (n = 29), Staphylococcus aureus (n = 28), Pseudomonas aeruginosa (n = 20), Enterobacter cloacae complex (n = 18), and Klebsiella pneumoniae (n = 17). For E.coli, susceptibility in the SOT antibiogram was significantly lower than those in the hospital-wide antibiogram in 2017/2018 for ampicillin (27% vs. 48%; P = 0.015), piperacillin/tazobactam (55% vs. 87%; P < 0.001), cefotaxime (59% vs. 88%; P < 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P < 0.001), but not significantly different for gentamicin (94% vs. 91%; P = 0.490), tobramycin (88% vs. 90%; P = 0.701) and amikacin (100% vs. 99%; P = 0.558). These findings were consistent throughout the study period in E.coli. There was no statistically significant difference between the SOT and hospital-wide antibiograms for other organisms. There were no significant differences in susceptibility between organ-specific antibiograms or transplant timing-specific antibiograms in 2012–2018. Conclusions We found that E.coli from the SOT population had a significantly lower sensitivity to all antimicrobials, except aminoglycosides, compared with those from the hospital-wide population. Other organisms had similar susceptibility to the hospital-wide population. Developing a SOT antibiogram will assist in revising and improving empiric treatment guidelines for this population.

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Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043731

Author(s):

Adnan Sharif ◽

Javeria Peracha ◽

David Winter ◽

Raoul Reulen ◽

Mike Hawkins

Keyword(s):

Organ Transplantation ◽

Record Linkage ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Study Cohort ◽

Solid Organ ◽

Post Transplantation ◽

Increased Risk ◽

Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

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Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

Journal of Fungi ◽

10.3390/jof7050327 ◽

2021 ◽

Vol 7 (5) ◽

pp. 327

Author(s):

Nipat Chuleerarux ◽

Achitpol Thongkam ◽

Kasama Manothummetha ◽

Saman Nematollahi ◽

Veronica Dioverti-Prono ◽

...

Keyword(s):

Systematic Review ◽

Invasive Aspergillosis ◽

Meta Analysis ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Effect Estimate ◽

Solid Organ ◽

Post Transplant ◽

Cmv Disease ◽

The Impact

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.

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A systematic review of post-transplant lymphoproliferative disorder after lung transplant.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e19046 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e19046-e19046

Author(s):

Mobeen Zaka Haider ◽

Zarlakhta Zamani ◽

Fnu Kiran ◽

Hasan Mehmood Mirza ◽

Muhammad Taqi ◽

...

Keyword(s):

Lymphoproliferative Disorder ◽

Lung Transplant ◽

Late Onset ◽

Adult Population ◽

Solid Organ Transplantation ◽

Chemotherapeutic Agents ◽

Solid Organ ◽

Transplant Recipients ◽

Post Transplant ◽

Lung Transplant Recipients

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]

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Posttransplant Lymphoproliferative Disease Presenting as an Extracranial Mass

Case Reports in Transplantation ◽

10.1155/2017/6401086 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5

Author(s):

Reuben J. Arasaratnam ◽

Alejandro Restrepo

Keyword(s):

Soft Tissue ◽

Early Recognition ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Antibody Therapy ◽

B Cell Lymphoma ◽

Lymphoproliferative Disease ◽

Solid Organ ◽

Tissue Mass ◽

Posttransplant Lymphoproliferative Disease

Posttransplant lymphoproliferative disease is a serious complication following stem cell and solid organ transplantation. Early recognition of the disease is important in facilitating timely therapy and improving long-term outcomes. We report a renal transplant recipient presenting with an extracranial frontoparietal soft tissue mass that was subsequently diagnosed as a B-cell lymphoma. The patient was treated successfully with immunosuppression reduction, anti-CD20 monoclonal antibody therapy, and cytotoxic chemotherapy. Our case highlights the importance of recognizing soft tissue masses in the head and neck as a potential clinical manifestation of PTLD in solid organ transplant recipients.

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