Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

Eshraghian, Ahad; Imanieh, Mohammad Hadi; Dehghani, Seyed Mohsen; Nikeghbalian, Saman; Shamsaeefar, Alireza; Barshans, Frouzan; Kazemi, Kourosh; Geramizadeh, Bita; Malek-Hosseini, Seyed Ali

doi:10.3748/wjg.v23.i7.1224

Cited by 31 publications

(20 citation statements)

References 39 publications

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“…The survival rate was significantly better in patients undergoing tacrolimus regimens compared to CsA (81.2% vs 50% after 5 years from the PTLD diagnosis)[29]. Multidisciplinary approaches that include IS weaning, interferon, surgery, radiotherapy and chemotherapy were attempted to reduce the incidence or recurrence from PTLDs[30].…”

Section: Resultsmentioning

confidence: 99%

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Manzia¹,

Angelico²,

Gazia³

et al. 2019

WJG

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BACKGROUNDImmunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients.AIMTo study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients.METHODSA systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTSEmerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences.CONCLUSIONThe selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

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Section: Resultsmentioning

confidence: 99%

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Manzia¹,

Angelico²,

Gazia³

et al. 2019

WJG

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“…This is in keeping with other published series in the literature with Ng reporting 5.3% of patients with PTLD at 10 years post‐LT in their cohort of 167 patients across North America. Another series from the Middle East reported 6.25% of pediatric LT recipients with PTLD …”

Section: Discussionmentioning

confidence: 98%

Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5 years

Sheikh

Chau

Evans

2018

Pediatric Transplantation

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Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low-dose steroids for the first year post-LT. Patients undergo a protocol biopsy at 1 year post-LT prior to stopping steroids, then at 5 years and every 5 years thereafter. Target tacrolimus levels are 5-8 μg/L and 3-5 μg/L after 3 and 12 months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5 years, respectively. A total of 43 patients (median age at LT 2.3 years) underwent a protocol biopsy at 1 year (16 male; median time post-LT 12.5 months), and 44 (20 male; median time post-LT 5.1 years) at 5 years. By 5 years, 3 had transferred to adult services; 1 was re-transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5 years. At 1 and 5 years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5 years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5 years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5 years, respectively). Tacrolimus levels at 5 years were slightly higher than anticipated (median trough level 5.8 μg/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1 year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5 years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5 years. However, the tacrolimus levels at 5 years were higher than planned and this may have played a role. Further evaluation is also required to determine the potential long-term adverse effects of corticosteroid use on linear growth and bone mineral density.

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“…10 PTLD are mostly from recipient-origin but can also occur from donor-origin and the main risk factors include being a pediatric recipient, having positive EBV titers, and the degree of immunosuppression. 11,12 The prognosis of PTLD is poor with a 5-year survival rate of around 50%. 9 Our patient had DLBCL, classified as a monomorphic B-cell type PTLD, which is seen 12-times more in posttransplant patients than the general population and has the highest risk 1 year after transplant.…”

Section: Discussionmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disorder Presenting as Ptosis, Fever, and Regression of Milestones 7 Months After Liver Transplant

Proaño

Margolis

Gandert

et al. 2020

Clin Pediatr (Phila)

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Post-transplant lymphoproliferative disorder after liver transplantation: Incidence, long-term survival and impact of serum tacrolimus level

Cited by 31 publications

References 39 publications

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5 years

Posttransplant Lymphoproliferative Disorder Presenting as Ptosis, Fever, and Regression of Milestones 7 Months After Liver Transplant

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