title: Pre-emptive rituximab based on viraemia and T cell reconstitution: a highly effective strategy for the prevention of Epstein-Barr virus-associated lymphoproliferative disease following stem cell transplantation.
abstract: This study investigated the efficacy of a pre-emptive strategy based on the combination of Epstein-Barr virus (EBV) viraemia and poor T cell reconstitution in preventing post-transplant lymphoproliferative disease (PTLD) following T cell depleted stem cell transplant (SCT). EBV viral load and immune reconstitution were prospectively monitored in 70 consecutive children undergoing SCT following reduced intensity conditioning with alemtuzumab. Patients who developed significant EBV viraemia (> 40 000 copies/ml blood) were treated pre-emptively with rituximab if they were within 3 months of SCT or their CD3 count was <0·3 × 10⁹ /l. Of 20/70 patients who developed significant EBV viraemia, 13 received pre-emptive rituximab. The incidence of PTLD was significantly reduced in the pre-emptive cohort compared to historical controls (1·4% vs. 21·7%, P = 0·003). This difference was more marked among viraemic patients (2·7% vs. 62·5%P < 0·0001). Patients treated with rituximab demonstrated significantly delayed B cell reconstitution at 1 year post-SCT but this was not associated with an increase in infectious mortality. In 6/6 patients >3 months post-SCT who had a CD3 count >0·3 × 10⁹ /l, reduced immunosuppression only resulted in successful resolution of EBV viraemia without PTLD. This strategy is safe and highly effective in preventing PTLD following T cell depleted SCT, and directs rituximab therapy to patients at highest risk of this complication.
authors.affiliation: Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Austen
authors.initials: A
authors.lastname: Worth
authors.forename: Rachel
authors.initials: R
authors.lastname: Conyers
authors.forename: Jonathon
authors.initials: J
authors.lastname: Cohen
authors.forename: Mamta
authors.initials: M
authors.lastname: Jagani
authors.forename: Robert
authors.initials: R
authors.lastname: Chiesa
authors.forename: Kanchana
authors.initials: K
authors.lastname: Rao
authors.forename: Nicholas
authors.initials: N
authors.lastname: Goulden
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D011446:Prospective Studies; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014766:Viremia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014775:Virus Activation; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D000069283:Rituximab