Rational management of posttransplant lymphoproliferative disorder in pediatric recipients

Kartik Praghakaran, Barbara Wise, Allen R Chen, Kathleen Schwarz, Paul Colombani

Research output: Contribution to journalArticle

Abstract

Background/Purpose: Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10% of pediatric transplant recipients with mortality rates up to 80%. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years. Methods: A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsyproven cases of PTLD and one probable case (8%). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an 'intent-to-treat' basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C. Results: Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients-progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patient's had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low- dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child With significant neurological sequelae. Conclusions: PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100% patient and graft survival.

Original languageEnglish (US)
Pages (from-to)112-116
Number of pages5
JournalJournal of Pediatric Surgery
Volume34
Issue number1
DOIs
StatePublished - Jan 1999

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Lymphoproliferative Disorders
Pediatrics
Immunosuppression
Tacrolimus
Human Herpesvirus 4
B-Cell Leukemia
Liver
Drug Therapy
Transplants
Epstein-Barr Virus Infections
Acyclovir
Cytarabine
Vincristine
B-Cell Lymphoma
Graft Survival
Prednisone
Viral Load
Methotrexate
Spain
Doxorubicin

Keywords

  • B cell lymphoma
  • Pediatric liver transplant
  • Posttransplant lymphoproliferative disorder

ASJC Scopus subject areas

  • Surgery

Cite this

Rational management of posttransplant lymphoproliferative disorder in pediatric recipients. / Praghakaran, Kartik; Wise, Barbara; Chen, Allen R; Schwarz, Kathleen; Colombani, Paul.

In: Journal of Pediatric Surgery, Vol. 34, No. 1, 01.1999, p. 112-116.

Research output: Contribution to journalArticle

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abstract = "Background/Purpose: Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10{\%} of pediatric transplant recipients with mortality rates up to 80{\%}. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years. Methods: A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsyproven cases of PTLD and one probable case (8{\%}). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an 'intent-to-treat' basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C. Results: Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients-progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patient's had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low- dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child With significant neurological sequelae. Conclusions: PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100{\%} patient and graft survival.",
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AB - Background/Purpose: Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10% of pediatric transplant recipients with mortality rates up to 80%. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years. Methods: A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsyproven cases of PTLD and one probable case (8%). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an 'intent-to-treat' basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C. Results: Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients-progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patient's had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low- dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child With significant neurological sequelae. Conclusions: PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100% patient and graft survival.

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