Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children's Oncology Group Report

Am J Transplant. 2012 Nov;12(11):3069-75. doi: 10.1111/j.1600-6143.2012.04206.x. Epub 2012 Aug 6.

Abstract

Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains problematic. A phase II trial adding rituximab to a low-dose cyclophosphamide and prednisone regimen was conducted for pediatric patients with Epstein-Barr virus (EBV) (+), CD20 (+) PTLD. Fifty-five patients were enrolled. Toxicity was similar for cycles of therapy containing rituximab versus those without. The complete remission (CR) rate was 69% (95% confidence interval (CI); 57%-84%). Of 12 patients with radiographic evidence of persistent disease at the end of therapy, eight were in CR 28 weeks later without further PTLD therapy. There were 10 deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2-year event-free survival (alive with functioning original allograft and no PTLD) was 71% (95% CI: 57%-82%) and overall survival was 83% (95% CI: 69%-91%) with median follow-up of 4.8 years. Due to small numbers, we were unable to determine significance of tumor histology, stage of disease, allograft type or early response to treatment on outcome. These data suggest rituximab combined with low-dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD following solid-organ transplantation.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Child
  • Child, Preschool
  • Confidence Intervals
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epstein-Barr Virus Infections / drug therapy
  • Epstein-Barr Virus Infections / etiology
  • Epstein-Barr Virus Infections / mortality
  • Epstein-Barr Virus Infections / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoproliferative Disorders / drug therapy*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / mortality
  • Lymphoproliferative Disorders / pathology
  • Male
  • Maximum Tolerated Dose
  • Organ Transplantation / adverse effects*
  • Organ Transplantation / methods
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prospective Studies
  • Risk Assessment
  • Rituximab
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Cyclophosphamide
  • Prednisone