NEW YORKA low-dose 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, and
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.