Early Signs And Risk Factors For The Increased Incidence Of Epstein-Barr Virus-Related Posttransplant Lymphoproliferative Diseases In Pediatric Liver Transplant Recipients Treated With Tacrolimus

Sokal, Étienne; Antunes, Hugo; Beguin, Claire; Bodéus, Monique; Wallemacq, Pierre; Goyet, Jean de Ville de; Reding, Raymond; Janssen, M.; Buts, Jean-Paul; Otté, Jean-Bernard

doi:10.1097/00007890-199711270-00011

Cited by 178 publications

(134 citation statements)

References 10 publications

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“…OKT3 induction is associated with fever, aseptic meningitis, and noncardiogenic pulmonary edema, as well as profound immunosuppression and an increased risk for opportunistic infections and neoplasia, especially posttransplant lymphoproliferative disease. 5,6,[15][16][17] In our study, the OKT3 group had the greatest rate of infections. Similar results were published by Reding et al, 18 who noted that 49% of infectious processes occurred in their OKT3 group.…”

Section: Discussionmentioning

confidence: 88%

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function

et al. 2001

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The addition of daclizumab (a human immunoglobulin G1 monoclonal antibody that blocks interleukin-2 receptors on T lymphocytes) to mycophenolate mofetil (MMF) and steroids is a new option for initial immunosuppression in patients undergoing liver transplantation (LT) with impaired renal function. We evaluated the efficacy and safety of daclizumab in preventing rejection in 25 patients with impaired kidney function undergoing LT. Patients with serum creatinine (Cr) levels greater than 2 mg/dL immediately before LT were administered initial immunosuppression with daclizumab, 1 mg/kg, in addition to MMF, 2 g/d, and methylprednisolone. Tacrolimus was added after kidney function improved (when Cr levels improved by >25% of initial value). Daclizumab-treated patients were compared retrospectively with 2 other groups of patients who underwent LT with kidney impairment (Cr > 2 mg/dL): 56 patients were administered OKT3 induction, and 48 patients were administered lowdose tacrolimus. The incidence of rejection and infection (bacterial, fungal, and viral), need for preoperative and postoperative dialysis, Cr level immediately post-LT and at 3 months, and graft and patient survival were analyzed. There was no difference among the groups in 3-month Cr levels or the incidence of rejection or fungal or viral infection. The daclizumab group had fewer bacterial infections (n ‫؍‬ 13) than the tacrolimus group (n ‫؍‬ 28) and significantly fewer than the OKT3 group (n ‫؍‬ 58; P ‫؍‬ .006). Only 1 patient (4%) in the daclizumab group required dialysis post-LT versus 13 patients in each of the other groups (OKT3, 23.21%; P < .05; tacrolimus, 27%). In the daclizumab group, 2-year patient and graft survival rates were statistically significant compared with the lowdose tacrolimus group (89% and 81% v 73% and 69%, respectively; P ‫؍‬ .06). There were no side effects related to daclizumab use, and all patients tolerated the drug well. In patients with impaired renal function before LT, daclizumab-based initial immunosuppression can be used safely to reduce the risk for infection and need for dialysis post-LT, with improved long-term graft and patient survival. (Liver Transpl 2001;7:220-225.)T here is no agreement on initial immunosuppressive regimens in patients undergoing liver transplantation (LT) with impaired renal function. [1][2][3] Suggested regimens include OKT3 induction in combination with azathioprine and steroids, with or without low doses of calcineurin inhibitors. [4][5][6] A new option in this circumstance is the use of daclizumab with mycophenolate mofetil (MMF) and steroids. Daclizumab is a human immunoglobulin G1 monoclonal antibody that blocks the ␣ chain of interleukin-2 receptors on activated T lymphocytes. [7][8][9] Previous studies have shown the efficacy of daclizumab in preventing rejection in kidney transplantation and LT without immediate side effects. [7][8][9][10][11] In particular, daclizumab does not cause cytokine release syndrome, neurotoxicity, or nephrotoxicity, which makes it an appealing alternative t...

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Section: Discussionmentioning

confidence: 88%

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function

et al. 2001

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“…Bacterial and fungal infections affect up 75% of patients and directly result in up to 50% of deaths. 1,11 Multiresistant organisms, such as methicillin-resistant Staphylococcus aureus, multiresistant Klebsiella, and vancomycin-resistant enterococcus, [25][26][27][28] The immunosuppressive management of neonates is difficult and rarely tailored to age. In most centers, neonates receive regimens similar to those for older patients, with protocols based on either cyclosporine or tacrolimus.…”

Section: Operative and Postoperative Considerationsmentioning

confidence: 99%

Liver transplantation in neonates

Sundaram

Alonso

Whitington

2003

Liver Transplantation

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Orthotopic liver transplantation (OLT) has evolved over the past two decades to become the standard of care for end-stage liver disease in infants and children. Technical advances, particularly the use of technical variant allografts, have permitted extension of OLT into a much younger and smaller population than previously possible. Major centers around the world now routinely perform OLT in infants with survival success equivalent to that in older children and adults. We are beginning to see a small population of school-aged children who were infant OLT recipients. The further extension of OLT into neonates is more recent, with only a few pediatric centers reporting survival success. Very little is known about this frontier of transplantation. Our intent is to provide an overview of neonatal OLT using all available data and our experience in the field. (Liver Transpl 2003;9:783-788.)F or the purpose of this review, neonatal orthotopic liver transplantation (OLT) is defined as transplantation performed in the first three months of life. This does not coincide with the usual definition of the neonate, infants in their first month of life. The extension to three months is necessary, however, because of the manner in which data regarding pediatric OLT have been collated. This division also holds because most diseases necessitating neonatal OLT produce liver failure at or near the time of birth. United Network for Organ Sharing (UNOS) data show that in 2001, 623 pediatric OLTs were performed in the United States. Of these transplantations, 167 were performed in children younger than one year of age and only eight in neonates. The number of neonatal OLT procedures has been varied over the past four years from eight to 14, with the peak in 2000. Patient and graft survival, 57% and 38% respectively, remain significantly lower than that of older children. 1,2 UNOS data show that infants three to 12 months old have graft and patient survival of 72.8 % and 82.1%, respectively. Children aged one to five years have 76.8% graft and 84.1% patient survival, and those older than six years have greater than 82% graft and 91% patient survival. These data demonstrate that transplantation in neonates presents unique medical and technical challenges. The complexities of liver transplantation in this age group have received relatively little attention in the medical literature. This review details the common indications for transplantation, addresses the multiple obstacles to successful transplantation, and explores strategies to improve survival and long-term outcomes in neonatal recipients. Defining the ProblemThe age distribution of reported neonatal OLTs is evenly distributed across the first three months of life. Woodle et al reported a series of 23 neonatal OLTs performed at three US centers: 28% were less than one month old, 35% were one to two months old, and 36% were two to three months old at the time of transplantation. 2 The youngest infant reported to undergo liver transplant was five days old. 3 The typical body weight...

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“…Because of the use of high doses of immunosuppressive agents and/or T cell depletion, these patients have impaired cellular immune responses and therefore cannot control the proliferation of EBV-infected B cells (6). The incidence of PTLD is a particular problem in the pediatric population, because a high proportion of young children are EBV seronegative and cannot mount a primary immune response to EBV while receiving immunosuppressive drugs (7)(8)(9). PTLD can be aggressive, with a rapidly lethal course, and current therapies have limited success (10).…”

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confidence: 99%

Generation of EBV-Specific CD4+ Cytotoxic T Cells from Virus Naive Individuals

Savoldo

Cubbage

Durett

et al. 2002

The Journal of Immunology

104

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Adoptive immunotherapy with EBV-specific CTL (EBV-CTL) effectively prevents and treats EBV-driven lymphoproliferation in immunocompromised hosts. EBV-seronegative solid organ transplant recipients are at high risk of EBV-driven lymphoproliferation because they lack EBV-specific memory T cells. For the same reason, standard techniques for generating EBV-CTL in vitro from EBV-naive individuals are unsuccessful. To overcome this problem, we compared several methods of expanding EBV-CTL from seronegative adults and children. First, the standard protocol, using EBV-transformed lymphoblastoid B cell lines (LCL) as the source of APC, was compared with protocols using EBV-Ag-loaded dendritic cells as APC. Surprisingly, the standard protocol effectively generated CTL from all seronegative adults. The additional finding of EBV-DNA in the peripheral blood of three of these four adults suggested that some individuals may develop cellular, but not humoral, immune responses to EBV. By contrast, LCL failed to reactivate EBV-CTL from any of the six EBV-seronegative children. EBV-Ag-loaded dendritic cells could expand EBV-CTL, but only in a minority of children. However, the selective expansion of CD25-expressing T cells, 9–11 days after activation with LCL alone, proved to be a simple and reliable method for generating EBV-CTL from all seronegative children. The majority of these CTL were CD4+ (71 ± 26%) and demonstrated HLA class II-restricted, EBV-specific killing. Our results suggest that a negative EBV serology does not accurately identify EBV-negative individuals. In addition, our method for selecting EBV-specific CTL from naive individuals by precursor cell enrichment may be applicable to the immunotherapy of cancer patients with a low frequency of tumor- or virus-specific CTL.

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Early Signs And Risk Factors For The Increased Incidence Of Epstein-Barr Virus-Related Posttransplant Lymphoproliferative Diseases In Pediatric Liver Transplant Recipients Treated With Tacrolimus

Cited by 178 publications

References 10 publications

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function

Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function

Liver transplantation in neonates

Generation of EBV-Specific CD4+ Cytotoxic T Cells from Virus Naive Individuals

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