A pilot study of chemoimmunotherapy (cyclophosphamide, prednisone, and rituximab) in patients with post-transplant lymphoproliferative disorder following solid organ transplantation.
OBJECTIVE
We have previously demonstrated a >80% complete response (CR) rate with cyclophosphamide/prednisone (Cy/Pred) chemotherapy alone in patients with post-transplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT), but only a 58% 2-year event-free survival. The response rate to immunotherapy (rituximab) is only about 46% with a 54% relapse/progression rate. In this study, we investigated the use of a combination of Cy/Pred with rituximab as treatment for this disease.


METHODS
Patients received two to six courses of cyclophosphamide (600 mg/m(2), on day 1 of each course) and prednisone (1 mg/kg, every 12 h x 10 doses), given every 3 weeks. The first two courses were given in combination with 4-6 weekly doses of rituximab (375 mg/m(2), i.v.). Imaging studies were done every 2 months to document response.


RESULTS
There were six PTLD patients (two fulminant); age, 4-23 year; sex, male:female (3:3); status post SOT (two cardiac, two liver, two renal); median onset, 39 months (10-144 months). Fifty percent were polyclonal, 100% were CD20+, and 83% were EBV+. The overall response rate was 100% (five CRs and one PR). All five CRs showed no evidence of disease, and one PR eventually progressed and died of fulminant disease. All allografts in surviving patients were functional. There was no grade III/IV toxicity and/or no infectious complications related to the combination of Cy/Pred with rituximab. Median follow-up was 12.5 months (range, 4-29 months).


CONCLUSIONS
These preliminary results suggest that the combination of Cy/Pred and targeted immunotherapy (rituximab) is well tolerated and may be more efficacious in patients with PTLD after SOT. Future prospective larger trials with longer follow-up investigating this combination will be required to confirm these preliminary results.
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000379:methods*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008232:Lymphoproliferative Disorders / Q000628:therapy*; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects*; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage*; D000069283:Rituximab; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D011241:Prednisone