Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation.
OBJECTIVE
To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) -positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD.


METHODS
Eligible patients received cyclophosphamide (600 mg/m2 intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles.


RESULTS
Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had > or = three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively.


CONCLUSIONS
This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.
Gross
Thomas G
TG
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA. tgross@chi.osu.edu
Bucuvalas
John C
JC
Park
Julie R
JR
Greiner
Timothy C
TC
Hinrich
Steven H
SH
Kaufman
Stuart S
SS
Langnas
Alan N
AN
McDonald
Ruth A
RA
Ryckman
Frederick C
FC
Shaw
Byers W
BW
Sudan
Debra L
DL
Lynch
James C
JC
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D016377:Organ Transplantation / Q000009:adverse effects* / Q000379:methods; D011241:Prednisone / Q000627:therapeutic use; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate