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Low-dose chemotherapy for children with post-transplant lymphoproliferative disease
1Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, OH 45237, USA.
Insights
Pediatric post-transplant lymphoproliferative disease (PTLD) is challenging to treat. A low-dose chemotherapy regimen of cyclophosphamide and prednisone showed an 82% complete remission rate in children who failed immune suppression reduction.
Area of Science:
- Pediatric Oncology
- Transplantation Immunology
Background:
- Post-transplant lymphoproliferative disease (PTLD) poses a significant risk to pediatric solid organ transplant recipients.
- Treatment challenges include managing chemotherapy toxicity, infection risk, and allograft maintenance.
Purpose of the Study:
- To evaluate the efficacy and tolerability of a low-dose chemotherapy regimen for pediatric PTLD refractory to immune suppression reduction.
Main Methods:
- A cohort of 39 children with PTLD who failed immune suppression reduction were treated.
- The regimen consisted of cyclophosphamide (600 mg/m2) and prednisone (2 mg/kg/day for 5 days) every 3 weeks for 6 cycles.
Main Results:
- An 82% complete remission rate was achieved.
- Graft survival was 90% with an overall 1-year survival of 86%.
- Relapse occurred in 22% of patients, with late-onset PTLD being more prone to relapse.
Conclusions:
- Low-dose cyclophosphamide and prednisone is a well-tolerated and effective treatment for pediatric PTLD unresponsive to immune suppression reduction.
- Salvage therapy with conventional chemotherapy was successful in some relapsed cases.
Abstract:
Children are at higher risk for developing post-transplant lymphoproliferative disease (PTLD) than adults. Successful treatment of PTLD following solid organ transplant is a therapeutic challenge due to the patients' increased toxicity from chemotherapy, increased susceptibility to life-threatening infections, and the necessity to maintain the allograft. Patients who do not tolerate reduction of immune suppression (i.e., graft rejection), or have PTLD that does not respond to immune suppression reduction, require more aggressive therapy and have a much poorer prognosis. We report 39 children with PTLD who failed reduction of immune suppression and were treated with a low-dose chemotherapy regimen of cyclophosphamide (600 mg/m2) and prednisone (2 mg/kg per day for 5 days) given every 3 weeks for 6 cycles. The complete remission rate was 82%. Graft survival was 90%. Relapse rate was 22%, with late-onset PTLD (> or =2 years from transplant) more likely to relapse. Of the seven patients with relapsed PTLD, four were salvaged with "conventional" non-Hodgkin's lymphoma chemotherapy. The overall 1-year survival for patients treated with low-dose chemotherapy was 86%. The estimated 2-year survival is 73%. This low-dose chemotherapy approach is well tolerated and effective for PTLD in children who fail reduction of immune suppression.