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Molecular Targeting of Post-transplant Lymphoproliferative Disorders

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Molecularly Targeted Therapy for Childhood Cancer

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Abstract

Post-transplant lymphoproliferative disorders (PTLD) represent a heterogeneous group of life-threatening lymphoproliferative disorders that can be observed in a transplant recipient. PTLD can occur in patients after solid organ transplantation (SOT) because of immunosuppression to prevent graft rejection (Penn et al. 1969), and continues to be a major cause of morbidity and mortality seen in about 10% of pediatric SOT recipients. There is a higher incidence in children following SOT than in adults (Ho et al. 1988; Swerdlow et al. 2000), with highest incidence of 20% following heart-lung transplant. PTLD occurs in hematopoietic stem cell transplantation (HSCT) recipients secondary to the immunosuppression of pre-HSCT preparative regimens, and the post-HSCT immunosuppression to prevent graft vs host disease (GVHD). PTLD in HSCT occurs at a lower rate than following SOT (approximately 1%), with the vast majority occurring within 6 months following HSCT (Bhatia et al. 1996; Curtis et al. 1999). Accordingly, few cases of PTLD have been reported after autologous HSCT (Lones et al. 2000; Nash et al. 2003). PTLD is associated with Epstein–Barr virus (EBV) and inadequate EBV immunity in the majority of cases. PTLD following HSCT is essentially all EBV-associated. EBV-negative PTLD occurs following SOT in as many as 30% of cases. (Leblond et al. 2001). The pathogenesis, treatment strategies and outcome differ from EBV-positive PTLD, as EBV-negative disease tends to require more aggressive therapy and portends a worse prognosis. This chapter will focus on EBV positive PTLD and molecularly targeted therapies in its prevention and treatment.

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Authors and Affiliations

  1. Division of Hematology/Oncology/BMT, The Ohio State University College of Medicine, 700 Children’s Drive, Columbus, OH, 43205, USA

    Thomas G. Gross

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Correspondence to Thomas G. Gross .

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Editors and Affiliations

  1. Director, Center for Childhood Cancer, Nationwide Children’s Hospital, The Research Institute, 700 Children’s Drive 332, Columbus, 43205, Ohio, USA

    Peter J. Houghton

  2. Johns Hopkins The Bunting & Blaustein Ca, Medicine Kimmel Comprehensive Cancer Cen, Orleans Street 1650, Baltimore, 21231, Maryland, USA

    Robert J. Arceci

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Wang, M., Gross, T.G. (2010). Molecular Targeting of Post-transplant Lymphoproliferative Disorders. In: Houghton, P., Arceci, R. (eds) Molecularly Targeted Therapy for Childhood Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69062-9_11

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