title: Adapted treatment of Epstein-Barr virus infection to prevent posttransplant lymphoproliferative disorder after heart transplantation.
abstract: Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.
authors.affiliation: Clinical Hematology Unit, CHU La Pitié Salpêtrière Hospital, APHP, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Choquet
authors.forename: S
authors.initials: S
authors.lastname: Varnous
authors.forename: C
authors.initials: C
authors.lastname: Deback
authors.forename: J L
authors.initials: JL
authors.lastname: Golmard
authors.forename: V
authors.initials: V
authors.lastname: Leblond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D016027:Heart Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008232:Lymphoproliferative Disorders / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D007166:Immunosuppressive Agents
keywords: Epstein-Barr virus; heart transplantation; immunosuppression; posttransplantation lymphoproliferative disease; rituximab