title: Treatment of posttransplant lymphoproliferative disease with rituximab: the remission, the relapse, and the complication.
abstract: BACKGROUND
  Rituximab, a humanized anti-CD20 monoclonal antibody, is a promising new tool for the treatment of posttransplant lymphoproliferative disease (PTLD), especially for patients transplanted with rejection prone transplants of vital organs, such as patients after lung transplantation. Thus far, no major complications have been described. We treated three lung transplant recipients with Rituximab because of PTLD.
  
  
  METHODS
  Patients were treated with four weekly doses of 375 mg/m2 of Rituximab. Epstein-Barr virus (EBV) DNA was monitored with quantitative-competitive polymerase chain reaction and circulating B cells with flow cytometry.
  
  
  RESULTS
  Treatment with Rituximab resulted in a complete remission in all patients without signs of or progression of bronchiolitis obliterans syndrome. Patient 1 relapsed after 2 months with a partly CD20-negative PTLD but is in stable remission after radiotherapy. Patient 2 is in complete remission 16 months after treatment, but patient 3 developed a hypogammaglobulinemia and died of invasive aspergillosis after 6 months. EBV DNA was detectable in the blood samples of patients 2 and 3 before treatment with Rituximab and became negative instantly after Rituximab. In all three patients, B cells are absent in the peripheral blood 7 months (at death), 16 months, and 16 months after treatment with Rituximab. Antiproliferating agents, such as mycophenolate mofetil (MMF), might prolong B-cell depletion.
  
  
  CONCLUSIONS
  Rituximab was effective for the treatment of PTLD without progression of transplant dysfunction in our patients. Complications were a partly CD20-negative relapse of PTLD and a hypogammaglobulinemia. Attention should be paid to immunoglobulin G (IgG) levels, especially in patients treated with antiproliferating agents such as MMF.
authors.affiliation: Dept. of Internal Medicine, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. e.a.m.verschuuren@int.azg.nl
authors.forename: Erik A M
authors.initials: EA
authors.lastname: Verschuuren
authors.forename: Servi J C
authors.initials: SJ
authors.lastname: Stevens
authors.forename: Gustaaf W
authors.initials: GW
authors.lastname: van Imhoff
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Middeldorp
authors.forename: Conny
authors.initials: C
authors.lastname: de Boer
authors.forename: Gerard
authors.initials: G
authors.lastname: Koëter
authors.forename: T Hauw
authors.initials: TH
authors.lastname: The
authors.forename: Wim
authors.initials: W
authors.lastname: van Der Bij
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000188:drug therapy*; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D004279:DNA, Viral; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000069283:Rituximab