title: Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation.
abstract: Lymphoproliferative disease (LPD) is a recognized complication of primary immunodeficiency (PID) and immunodysregulatory syndromes. Historically, it has a very poor outcome. For patients surviving LPD, myeloablative hematopoietic stem cell transplantation (SCT) was the only cure for the underlying PID, with a high risk of developing posttransplantation complications, including recurrent lymphoproliferative disease. We describe 8 patients with a range of PID and immunodysregulatory syndromes complicated by LPD. After initial treatment of the LPD (including the use of anti-CD20 monoclonal antibody, rituximab, in 6 of the patients), all patients underwent reduced-intensity conditioning (RIC) SCT with prospective monitoring for Epstein-Barr virus (EBV) viremia. After transplantation, 3 patients received rituximab, and 3 patients received prophylactic EBV-specific cytotoxic T-lymphocytes. Only 1 patient developed recurrent LPD posttransplantation, which responded to rituximab. All patients who underwent transplantation survive free of LPD and are cured of their PID at a median follow-up of 4 years (range, 1-7 years). With careful monitoring and pre-emptive therapy, we advocate this RIC SCT approach to patients with PID who have pre-existing EBV-LPD.
authors.affiliation: Department of Clinical Immunology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cohen
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: Julia
authors.initials: J
authors.lastname: Harvey
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Cale
authors.initials: C
authors.lastname: Cathy
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: David
authors.initials: D
authors.lastname: Cubitt
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000628:therapy* / Q000821:virology; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000628:therapy* / Q000821:virology; D008297:Male; D011446:Prospective Studies; D000069283:Rituximab; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D019562:Viral Load; D014766:Viremia / Q000209:etiology / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000069283:Rituximab