scholarly journals Incidence and Outcomes of Post-Transplant Lymphoproliferative Disease after 5365 Solid Organ Transplants over a 20 Year Period at 2 UK Transplant Centres

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 888-888
Author(s):  
Anna Santarsieri ◽  
Andrew Butler ◽  
William Gelson ◽  
Stephen Pettit ◽  
John F Rudge ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
First Year ◽  
Solid Organ ◽  
Line Treatment ◽  
First Line ◽  
Post Transplant

Abstract Background: Post-transplant lymphoproliferative disease (PTLD) confers a high morbidity and mortality in a vulnerable population. We present the epidemiology and outcomes of PTLD in a large UK cohort of solid organ transplant (SOT) recipients who were transplanted over a 20-year period. Methods: This is a retrospective study of 5365 SOT recipients who had their first transplant between 2000 and 2021 at two UK transplant centres (Addenbrooke's Hospital and Papworth Hospital). We reviewed the records of all patients and found 142 who subsequently developed PTLD. For each type of transplant, we calculated the incidence rate of PTLD and cumulative incidence using a competing risk of death model. Survival was compared with the age-adjusted life expectancy of the UK population using the National life tables and a landmark analysis was performed to compare overall survival (OS) of PTLD patients from the date of diagnosis with the background survival of the transplant population. To compare treatment outcomes, a subset of 90 cases of monomorphic PTLD, DLBCL subtype were identified. 66 were treated with first-line Rituximab monotherapy and 24 received first-line R-Chemotherapy. Demographics, treatment response, and survival data were analysed with univariate and multivariate analysis to identify covariates associated with death in the first year post diagnosis of PTLD. Results: With a median follow-up time of 5.3 years, 142 of 5365 solid organ transplant recipients have developed PTLD (56/1965 kidney, 22/1428 liver, 12/327 simultaneous kidney-pancreas (SPK), 21/113 multivisceral (MVT), 10/778 heart, 15/503 bilateral lung, 3/148 single lung and 3/85 heart and lung). The incidence rate of PTLD was highest in the first year post-transplant in lung and MVT recipients. Cumulative incidence (shown in Figure 1) was 18% at 5 years post-MVT and 1-3% at 5 years following the other SOT types. Cumulative incidence was lowest for liver and heart transplants and was 10% at 20 years post-kidney transplantation. Median OS following SOT was 16 years which is significantly reduced compared with the age-adjusted UK population. There is a relatively high early mortality rate following diagnosis of PTLD and only patients surviving two years post diagnosis regained a similar longer-term survival to the non-PTLD SOT cohort. Treatment with rituximab monotherapy (RM) is now a standard of care for monomorphic PTLD 1. Outcomes for monomorphic patients were compared between those treated with RM (n=66, median follow-up 2.2 y) and R-Chemotherapy (n=24, median follow-up 5.2 y). The two groups were well matched for age and IPI. Of the 66 RM patients, 22 (33%) achieved complete remission with RM and required no further treatment. A further 18 (27%) patients achieved remission following further treatment with chemotherapy/surgery/CTL. 6/66 (9%) patients died of progressive disease (PD), 9/66 (14%) died pre-remission of non-PTLD causes and 11/66 (17%) died in remission of unrelated causes. In the R-Chemotherapy group, 22 patients received R-CHOP and 2 received R-CVP (n=24). 8 (33%) patients are alive and in remission after first line treatment and a further 3 patients (13%) after second line treatment. 2/24 (8%) patients died of PD, 4/24 (17%) died pre-remission of non-PTLD causes and 7/24 (30%) died post-remission of unrelated causes. There is no significant difference in OS between the two groups. Only a minority of deaths were due to PD and death from non-lymphoma causes pre and post remission remain considerably higher than non-PTLD SOT patients up to 2 years post treatment (Figure 1). Multivariate analysis of all 90 monomorphic PTLD patients identified IPI3+ as the strongest pre-treatment variable associating with inferior 1 year OS. Interestingly IPI3+ did not retain this significance when R-chemo patients were analysed alone. Conclusion: With this large SOT dataset we have mapped the cumulative incidence of PTLD over a 20 year period and highlight transplanted organ-specific differences in PTLD incidence over time. Treating monomorphic DLBL patients first-line with RM rather than R-chemotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes pre- and post-treatment remains high with both treatment approaches, with poor OS compared with age-matched non-PTLD SOT recipients. 1Trappe et al. Lancet Oncol; 2012 13(2):196-206 Figure 1 Figure 1. Disclosures Santarsieri: Janssen: Honoraria. Uttenthal: Roche: Other; Takeda: Other; Jazz: Other. Follows: Janssen, Abvie, Roche, AZ: Other.

Low Incidence and Successful Treatment of Post-Transplant Lymphoproliferative Disorders (PTLD) among 1,513 Patients Undergoing Liver Transplant Procedures.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 513-513
Author(s):  
Corrado Tarella ◽  
Ornella Perotto ◽  
Roberto Passera ◽  
Renato Romagnoli ◽  
Alessandro Franchello ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Transplant ◽  
Cumulative Incidence ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Large Series ◽  
Competing Risk ◽  
Solid Organ ◽  
Post Transplant

Abstract Introduction. Post-transplant lymphoproliferative disorder (PTLD) is a serious complication due to immunosuppression in solid organ transplant recipients. The incidence is quite variable and the outcome has been reported to be often fatal, although improvements have been observed since the introduction of Rituximab. Aim of the study. To evaluate: frequency, risk factors, and outcome of PTLD in a large series of Liver Transplant (LT). Patients and Methods. Data have been collected on 1,513 patients who underwent LT (127 had one to four re-LT, for a total of 1,648 procedures), over the last 15 yrs. PTLD were diagnosed by histology and immunophenotipical analysis on biopsy specimens. Several parameters were evaluated for possible association with PTLD occurrence, including age, sex, liver disease and HCV state of LT recipient, presence of hepatocellular carcinoma, time elapsed from LT to PTLD, main immunosuppressant therapy (cyclosporine vs. tacrolimus), other drugs for graft rejection. The cumulative incidence of PTLD was determined using the Fine and Gray competing risk regression model. Results. At a median follow-up of 62 mos., 1,224 out of 1,513 patients are alive, with a 5-yr Overall Survival (OS) projection of 80% (see Figure 1). So far, 18 PTLD have been recorded, with a cumulative incidence of 1.0, 1.9 and 4.2% at 5, 10 and 15 yrs respectively. Median time of PTLD occurrence was 32 mos. (range 2–155) since LT. On competing risk multivariate analysis, the use of tacrolimus vs. cyclosporine A was the only factor associated with increased risk of PTLD (SDHR: 2.79, p=0.032). Treatment for PTLD included: i. reduction or discontinuation (4 cases) of the immunosuppression; ii. chemotherapy (15 cases); in addition, Rituximab was delivered to 11 patients (combined with chemotherapy in 5); treatment resulted in Complete Remission in 14 patients, good Partial Remission (PR) in 4; one patient had a transient PR soon followed by disease progression; this was the only patient dying for PTLD; 2 more patients died for causes other than PTLD; at present, at a median follow up of 30 mos., 15 out of the 18 PTLD patients are alive, with a 5-yr OS projection of 88% (see Figure 2). Conclusions. The overall incidence of PTLD in this large series of LT is among the lowest reported so far in patients receiving solid organ transplant; the use of tacrolimus is confirmed as a significant risk factor for PTLD; the outcome of PTLD seems definitely improved; the availability of Rituximab is quite likely to have contributed to the prolonged survival observed. Based on the results of this study, the exclusion of patients with a previous history of lymphoproliferative disease from LT procedures seems questionable. Figure 1. Overall survival of 1,513 patients undergoing LT Figure 1. Overall survival of 1,513 patients undergoing LT Figure 2. Overall survival of 18 patients developing PTLD Figure 2. Overall survival of 18 patients developing PTLD

scholarly journals 572. Antiviral Toxicities Among Pediatric Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S351-S351
Author(s):  
Kevin J Downes ◽  
Anna Sharova ◽  
Marina Mitrou ◽  
Molly Hayes ◽  
Despoina Galetaki ◽  
...  
Keyword(s):  
Medication Management ◽  
Organ Transplant ◽  
Kidney Injury ◽  
Solid Organ Transplant ◽  
Incidence Rates ◽  
First Year ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Disease

Abstract Background Ganciclovir (GCV) and valganciclovir (VGCV) are used for prophylaxis (PPX) and treatment for CMV in pediatric solid organ transplant (SOT) recipients, but the frequency and impact of toxicities from these medications are not well described. Methods Retrospective cohort study of children undergoing SOT at Children’s Hospital of Philadelphia from Jan 2012 - Jun 2018. EMR were reviewed to identify laboratory-based toxicities between 15 days and 1 year post-transplant; medication management within 14 days of toxicity onset was recorded. Toxicities were defined as GCV or VGCV-associated if a patient was on the antiviral at toxicity onset. We defined acute kidney injury (AKI) as ≥50% change in creatinine (Cr) from 30 days prior, leukopenia as WBC < 3500/µL, neutropenia as ANC < 1000/µL, and thrombocytopenia as < 100K/µL. Incidence rates of toxicities on PPX and treatment were compared to rates during no antiviral using univariate Poisson regression. Results 285 children received 299 SOTs: 108 liver, 91 kidney, 69 heart, 31 lung. Nearly half (46%) of toxicities during the first year after transplant occurred while on GCV or VGCV PPX or treatment, but their use accounted for only 23% of all follow-up time. Receipt of VGCV and GCV PPX and treatment were associated with significantly higher incidence rates of toxicities compared to no antiviral (Fig 1). Of 259 GCV or VGCV-associated toxicities, 44% (n=113) were leukopenia, 26% (66) neutropenia, 26% (66) AKI, and 6% (15) thrombocytopenia (Table 1). Most recipients of VGCV PPX (64%) sustained at least one toxicity while on PPX. AKI during VGCV PPX led to stopping/dose-adjusting of VGCV in 43% and of immunosuppression in 57% of cases. Neutropenia during VGCV PPX resulted in stopping/dose-adjusting of VGCV in 63%, of immunosuppression in 36%, and of TMPX/SMX PPX in 36% of cases. During VGCV PPX, 81% of AKI was stage II/III (≥100% change in Cr) and 65% of neutropenia was severe (< 500/µL); 11% of both AKI (n=6) and neutropenia (n=7) during VGCV PPX resulted in hospitalization. Figure 1. Incidence Rates of Toxicities from Day 15 through 1 Year After Transplant Table 1. Antiviral Use and Toxicity 2 Weeks to 1 Year After Transplant Conclusion GCV and VGCV use was associated with significant renal and hematological toxicities in pediatric SOT recipients. While VGCV and GCV are effective at preventing CMV disease in pediatric SOT, clinicians should consider risk of toxicity when evaluating CMV prevention strategies. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

CD30 in pediatric post-transplant lymphoproliferative disease after solid organ transplant: characterization of a new therapeutic target

2014 ◽  
Vol 56 (3) ◽  
pp. 832-833 ◽  
Author(s):  
Tilmann Schober ◽  
Theodor Framke ◽  
Anika Großhennig ◽  
Christoph Klein ◽  
Hans Kreipe ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
Solid Organ ◽  
Post Transplant

Measles, Mumps, Rubella, and Varicella Zoster Virus Serology and Infections in Solid Organ Transplant Recipients During the First Year Posttransplantation

2020 ◽  
Author(s):  
Omid Rezahosseini ◽  
Søren Schwartz Sørensen ◽  
Michael Perch ◽  
Christina Ekenberg ◽  
Dina Leth Møller ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Solid Organ ◽  
Varicella Zoster ◽  
Severe Infections ◽  
One Year ◽  
A Prospective Study

Abstract Background Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients. Methods This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection. Results Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR. Conclusions A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT.

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