Use of Foscarnet Therapy for EBV Infection following Control of PTLD with Enhancement of Cellular Immunity in a Lung-Transplant Recipient

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation with an annual incidence rate of 3–5% in lung-transplant recipients. Pathogenesis indicates a strong association with functional over-immunosuppression and EBV infection. Clinical improvement is generally observed with reduction in immunosuppression intensity alone. We present a case of a 24-year-old woman with EBV-associated PTLD following lung transplant where decreasing the immunosuppression improved PTLD but was ineffective against controlling the EBV infection. Foscarnet in combination with immunoglobulins was successfully administered to cause a remission of the EBV infection. This is the second case reported of a persistent EBV infection after reducing immunosuppression levels and evidence of PTLD remission that required foscarnet for EBV infection control.

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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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Gastrointestinal Involvement of Posttransplant Lymphoproliferative Disorder in Lung Transplant Recipients: Report of a Case

Diseases of the Colon & Rectum ◽

10.1007/s10350-005-0116-7 ◽

2005 ◽

Vol 48 (11) ◽

pp. 2144-2147 ◽

Cited By ~ 11

Author(s):

David Shitrit ◽

Ariella Bar-Gil Shitrit ◽

Ram Dickman ◽

Gidon Sahar ◽

Milton Saute ◽

...

Keyword(s):

Lymphoproliferative Disorder ◽

Lung Transplant ◽

Transplant Recipients ◽

Posttransplant Lymphoproliferative Disorder ◽

Gastrointestinal Involvement ◽

Lung Transplant Recipients

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1103. Improving Perioperative Prophylactic Antimicrobial Guideline Concordance in Liver and Lung Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.967 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S391-S392

Author(s):

Cynthia T Nguyen ◽

Rachel Marrs ◽

Jennifer Pisano ◽

Natasha N Pettit ◽

Lisa Potter

Keyword(s):

Antimicrobial Stewardship ◽

Lung Transplant ◽

Small Sample Size ◽

Solid Organ Transplantation ◽

Composite Endpoint ◽

Small Sample ◽

Solid Organ ◽

Transplant Recipients ◽

Modifiable Factor ◽

Lung Transplant Recipients

Abstract Background Surgical site infection (SSI) is a common complication among patients undergoing solid-organ transplantation. Administration of perioperative antimicrobials is one modifiable factor that may reduce the risk of SSIs. We sought to evaluate antimicrobial stewardship efforts to improve concordance of perioperative antimicrobial selection (AS) and dose timing (DT) with the institution’s perioperative antimicrobial guidelines among liver (LVR) and lung transplant recipients (LNG). Methods This was a single-center, observational study of LVR and LNG between January 1, 2017 and December 31, 2018. Patients receiving antimicrobials for the treatment of infection immediately prior to transplant were excluded. Throughout the study period, several interventions were performed, including: updating AS and DT protocols (2017 Q2) and preoperative order sets (2017 Q4), improving availability of antibiotics in the operating room (2018 Q1), and most recently developing a guideline and providing education for intraoperative redosing based on renal function (2018 Q3). The primary outcome was overall guideline concordance (GC). This was a composite endpoint including preoperative and intraoperative AS and DT, based on the institution’s guideline. Secondary outcomes included SSI rates based on the CDC National Healthcare Safety Network definition and rate of new C. difficile or vancomycin-resistant Enterococci infection or colonization. Results Among 112 patient screened, 79 patients were included (45 LNG and 34 LVR). The median age was 60 years and BMI was 26.5 kg/m2. The median procedure length was 7.8 hours for LNG and 6.9 hours for LVR. Results are shown in Table 1, Figure 1 and Figure 2. All GC rates demonstrate improvements over time, except for intraoperative DT for LNG. Conclusion Limited by a small sample size, our study demonstrates that noninvasive antimicrobial stewardship strategies can yield improvements in GC. Disclosures All authors: No reported disclosures.

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Posttransplant Lymphoproliferative Disorder in Adult Lung Transplant Recipients: A Report on Twenty-Seven Patients.

Blood ◽

10.1182/blood.v110.11.4425.4425 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4425-4425

Author(s):

Sophie D. Stein ◽

Jamal Misleh ◽

Vivek Ahya ◽

Robert Kotloff ◽

Jason Christie ◽

...

Keyword(s):

Surgical Resection ◽

Lymphoproliferative Disorder ◽

Lung Transplant ◽

Radiation Treatment ◽

Case Series ◽

Complete Response ◽

Transplant Recipients ◽

Posttransplant Lymphoproliferative Disorder ◽

Primary Treatment Modality ◽

Lung Transplant Recipients

Abstract Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. We report a case series on the diagnosis, treatment and outcome of PTLD in lung transplant recipients. From 1991 to 2006, 27 (5%) of the 502 lung transplant recipients at our institution developed PTLD. The median age at transplant was 51.5 years (range 21–65 years) and the median time from transplant to PTLD diagnosis was 33.7 months (range 1–174 months). Most cases had an elevated LDH (86%) and were EBV-positive (85%). Of the cases tested (n=14), 64% were monoclonal. PTLD was most commonly diagnosed in the lung (56%) and gastrointestinal tract (26%). Three patients were diagnosed at autopsy, while the remaining 24 received therapy. Eight patients were initially treated with reduced immunosuppression (RI) alone, but only 3 (38%) obtained a complete response (CR). Rituxan (R) was used alone (n=3) or in combination with RI (n=3) as initial therapy in six patients, four of whom obtained a CR. Five patients utilized RI +/− surgical resection as a primary treatment modality, all of whom achieved a CR. However, all of them relapsed and required further treatment. Of these five patients initially treated with RI +/− surgical resection, a CR was reestablished in 3 using rituxan alone (1/3), combined rituxan and reduced immunosuppression (1/3) and radiation treatment alone (1/3). The remaining five patients from the 24 patients receiving induction therapy for PTLD were given other treatments. With an average follow-up of 28 months (range 1-130 months), 81% of patients have died. However, only 18% of deaths were directly related to progressive PTLD. The remaining 17 deaths were due to: infection unrelated to PTLD treatment (15%), multi-organ failure (7%), graft failure not due to RI (30%), stroke (4%), and renal failure (4%). Most deaths can be attributed to disease specific and posttransplant complications rather than PTLD. Although an unfortunate diagnosis, PTLD is responsive to therapy, particularly reduced immunosuppression and rituximab.

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Respiratory Viruses in Solid Organ Transplant Recipients

Viruses ◽

10.3390/v13112146 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2146

Author(s):

Roni Bitterman ◽

Deepali Kumar

Keyword(s):

Lung Transplant ◽

Viral Infections ◽

Solid Organ Transplantation ◽

Clinical Manifestations ◽

Respiratory Viruses ◽

Solid Organ ◽

Transplant Recipients ◽

Increased Risk ◽

Respiratory Viral Infections ◽

Lung Transplant Recipients

Solid organ transplantation is often lifesaving, but does carry an increased risk of infection. Respiratory viral infections are one of the most prevalent infections, and are a cause of significant morbidity and mortality, especially among lung transplant recipients. There is also data to suggest an association with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. Respiratory viral infections can appear at any time post-transplant and are usually acquired in the community. All respiratory viral infections share similar clinical manifestations and are all currently diagnosed using nucleic acid testing. Influenza has good treatment options and prevention strategies, although these are hampered by resistance to neuraminidase inhibitors and lower vaccine immunogenicity in the transplant population. Other respiratory viruses, unfortunately, have limited treatments and preventive methods. This review summarizes the epidemiology, clinical manifestations, therapies and preventive measures for clinically significant RNA and DNA respiratory viruses, with the exception of SARS-CoV-2. This area is fast evolving and hopefully the coming decades will bring us new antivirals, immunologic treatments and vaccines.

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Epidemiology of Cryptococcosis and Cryptococcal Meningitis in a Large Retrospective Cohort of Patients After Solid Organ Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx004 ◽

2017 ◽

Vol 4 (1) ◽

Cited By ~ 21

Author(s):

Ige A. George ◽

Carlos A. Q. Santos ◽

Margaret A. Olsen ◽

William G. Powderly

Keyword(s):

Kidney Transplant ◽

Median Time ◽

Lung Transplant ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Risk Of Death ◽

Increased Risk ◽

Lung Transplant Recipients

Abstract Background Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT. Methods We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006–2012), New York (2006–2011), and California (2004–2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified. Results A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4–2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5–1816), heart (195 days; range, 4–1061), and liver (200 days; range, 4–1581) compared with kidney transplant recipients (616 days; range, 12–2393; P < .001, log rank test). Very early-onset disease (<30 days after transplantation) more frequently occurred in liver and lung transplant recipients. Lung transplant recipients had the highest risk of cryptococcosis (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.21–3.60). Cryptococcosis was associated with death (HR, 2.29; 95% CI, 1.68–3.11), after adjusting for age, type of SOT, and other comorbidities. Conclusions Cryptococcosis is rare after SOT, but it is associated with significantly increased risk of death. Lung transplant recipients are at highest risk for cryptococcosis among SOTs. Nonkidney transplants have earlier onset of cryptococcosis and higher risk of death compared with kidney transplant recipients.

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