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THERAPEUTIC CONTROVERSIES

Role of Chemotherapy and Rituximab for Treatment of Posttransplant Lymphoproliferative Disorder in Solid Organ Transplantation

at time of writing, PharmD Student, College of Pharmacy, University of Florida, Gainesville, FL; now, Pharmacy Practice Resident, Florida Hospital, Orlando, FL

Masha SH Lam, PharmD BCOP

Oncology Pharmacist, Hematology/Oncology Infusion Clinic, Kaiser Permanente Health Plan, Walnut Creek, CA

Amy Rosenberg, PharmD BCPS

Clinical Pharmacy Specialist, Lung Transplantation, Shands at the University of Florida; Clinical Assistant Professor, College of Pharmacy, University of Florida

Reprints: Dr. Lam, 1425 S. Main St., Walnut Creek, CA 94596, fax 925/295-7370, mlam102108{at}yahoo.com

OBJECTIVE: To evaluate the role of chemotherapy and/or rituximab for treatment of posttransplant lymphoproliferative disorder (PTLD) in solid organ transplantation.

DATA SOURCES: A MEDLINE search (1966-May 2007) was conducted using the key words posttransplant lymphoproliferative disorder, solid organ transplantation, chemotherapy, and rituximab. References of relevant articles and abstracts from recent hematology, oncology, and transplantation scientific meetings (2004-May 2007) were also reviewed.

STUDY SELECTION AND DATA EXTRACTION: Prospective and retrospective studies identified from the data sources were evaluated, and all information deemed relevant was included for this review.

DATA SYNTHESIS: Overall response rates ranged from 53% to 68%, 25% to 83%, and 74% to 100% for rituximab monotherapy, chemotherapy, and chemotherapy plus rituximab, respectively. Positive response to treatment was influenced by prognostic factors, including presence of Epstein-Barr virus in tumor cells, normal lactate dehydrogenase levels, good performance status, early disease onset after transplantation, and early disease stages. These factors in study patients likely contribute to the variability in response rates seen between treatment options. Severe adverse effects, ranging from grade 3 neutropenia to infection resulting in death, occurred more frequently in patients receiving chemotherapy than in patients receiving only rituximab.

CONCLUSIONS: Although reduction in immunosuppressive medications remains the first-line therapy for PTLD treatment, many cases do not respond to this treatment alone, especially monomorphic or more aggressive cases of lymphoma. Therefore, it is reasonable to begin active treatment including rituximab and/or chemotherapy initially, along with reduction in immunosuppression in many cases. Further prospective, comparative studies are urgently needed to confirm the efficacy of these treatment strategies as well as to clarify which subset of patients may benefit most from them.

Key Words: chemotherapy, posttransplant lymphoproliferative disorder, solid organ transplantation, rituximab

Published Online, September 11, 2007. www.theannals.com, DOI 10.1345/aph.1K175