Detection and Cytotoxic T Lymphocyte Therapy of Post-Transplant Lymphoproliferative Disorder After Liver Transplant

Study Description

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Brief Summary:

Despite advances in medical and gene therapy, orthotopic liver transplantation remains the only definitive therapeutic option for children with end-stage liver disease. Recent advances in pre-, intra-, and early post-transplant care have resulted in a dramatic improvement in survival of the pediatric liver transplant patient. The broad long-range goal of our research program is directed at enhancing the patient's long-term survival. Our primary focus relates to obligate life-long immunosuppression, with its inherent complications including severe infection and development of cancer. These two complications come together in a single disease, Epstein-Barr Virus (EBV)- associated post-transplant lymphoproliferative disorder (PTLD). EBV, a latent human lymphotrophic herpes virus infects and immortalizes B cells. Primary infection usually occurs via salivary exchange and results in a mild, self-limited illness followed by life-long EBV-specific T cell controlled EBV latency. T cell-based immunosuppression prevents allograft rejection, however, it also suppresses cytotoxic T lymphocyte (CTL) function, generating an environment in which EBV-infected cells can proliferate. Patients receiving life-long T cell-based immunosuppression have an increased risk of developing PTLD due to their inability to produce normal immunoregulatory responses. This disease is particularly devastating to the pediatric patient as its incidence is at least 4-fold greater than in the adult liver transplant patient population. In fact, PTLD is the number one cause of death following pediatric liver transplantation. At this time, there is no definitive method of prospectively detecting, diagnosing, or treating PTLD, and current treatment protocols place the liver allograft and patient at risk. Therefore, a diagnostic tool that is both sensitive and specific, and a treatment strategy with low toxicity are greatly needed to decrease the morbidity and mortality suffered by the pediatric liver transplant patient with PTLD. Our proposed studies will support our hypothesis that the combination of a persistently elevated EBV load in the setting of a diminished immune response to EBV will be an early risk indicator associated with PTLD development, and that pre-emptive treatment utilizing autologous adoptive EBV-specific CTL immunotherapy will provide a low toxicity treatment option.

Condition or disease	Intervention/treatment	Phase
Liver Disease; Lymphoproliferative Disorders	Biological: EBV-specific autologous CTL	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	50 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Study Start Date :	May 2002
Study Completion Date :	December 2007

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	1 Month to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Pediatric patients s/p orthotopic liver transplantation

Contacts and Locations

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Locations

United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

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ClinicalTrials.gov Identifier:	NCT00063648 History of Changes
Other Study ID Numbers:	PTLD (completed)
First Posted:	July 3, 2003
Last Update Posted:	January 13, 2010
Last Verified:	January 2010

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

PTLD; CTL Therapy; Post-transplant lymphoproliferative disorder

Additional relevant MeSH terms:

Liver Diseases; Lymphoproliferative Disorders; Digestive System Diseases	Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases