NEW YORK—A low-dose cyclophosphamide(Drug information on cyclophosphamide)/prednisone regimen is effective for treating children with refractory lymphoproliferative disease after a solid organ transplant, according to results of a prospective study including 36 children. The total response rate was 86% for this group, which is the largest series of post-transplant lymphoproliferative disorder (PTLD) patients treated uniformly with chemotherapy. Two-year overall survival was 73%.
While the results are "encouraging," more work needs to be done, said Thomas G. Gross, MD, PhD, director, Division of Pediatric Hematology/Oncology, Ohio State University School of Medicine, Columbus. "We need to make some improvements in decreasing the relapse rate, in treating relapsed disease, and in treating patients with fulminant PTLD, which continues to be a difficult group," Dr. Gross said at the First International Symposium on Childhood and Adolescent Non-Hodgkin’s Lymphoma.
The next logical step, Dr. Gross said, is to add an antibody therapy to this "backbone" of chemotherapy. Notably, researchers from Columbia University are piloting a "more aggressive" therapy of cyclophosphamide, prednisone(Drug information on prednisone), and rituximab(Drug information on rituximab) (Rituxan) (CPR) in patients with refractory PTLD (Orjuela M et al: Clin Cancer Res, in press).
In addition, a currently pending Children’s Oncology Group (COG) trial will evaluate the CPR regimen in children, adolescents, and young adults with CD20-positive PTLD. Dr. Gross, the principal investigator in that trial, said he hopes this could be a way to achieve tumor control without adding toxicity.
According to preliminary results from the Columbia group’s pilot study, including data on seven treated patients, "response rates have been excellent, and toxicity has been low," Dr. Gross said. "Interestingly, two patients presented with fulminant disease, and one is now greater than 1 year out in continuous complete remission."
The Gold Standard
The gold standard for the treatment of PTLD in the solid organ transplant population is withdrawal or reduction of immunosuppression plus or minus antiviral therapy, Dr. Gross said. With this approach, remission rates of from 40% to 60% have been reported. For patients with refractory PTLD, or those who do not respond or have a complication upon withdrawal or reduction of immunosuppression, outcomes are historically poor due to risk of rejection, infection, and increased susceptibility to treatment-related toxicity.
