First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Disease Patient and Review of the Literature

• Main Authors: Maddalena Migliavacca, Andrea Assanelli, Maurilio Ponzoni, Roberta Pajno, Federica Barzaghi, Fabio Giglio, Francesca Ferrua, Marta Frittoli, Immacolata Brigida, Francesca Dionisio, Roberto Nicoletti, Miriam Casiraghi, Maria Grazia Roncarolo, Claudio Doglioni, Jacopo Peccatori, Fabio Ciceri, Maria Pia Cicalese, Alessandro Aiuti
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-02-01
• Series: Frontiers in Immunology
• Subjects: adenosine deaminase-deficient severe combined immunodeficiency disease; lymphoma; plasmablastic lymphoma; primary immunodeficiency; gene therapy; gene therapy for rare diseases
• Online Access: http://journal.frontiersin.org/article/10.3389/fimmu.2018.00113/full

Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term. To date, eight cases of lymphomas have been described in ADA-SCID patients. Here we report the first case of plasmablastic lymphoma occurring in a young adult with ADA-SCID on long-term ERT, which turned out to be Epstein–Barr virus associated. The patient previously received infusions of genetically modified T cells. A cumulative analysis of the eight published cases of lymphoma from 1992 to date, and the case here described, reveals a high mortality (89%). The most common form is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT. The significant incidence of immunodeficiency-associated lymphoproliferative disorders and poor survival of patients developing this complication highlight the priority in finding a prompt curative treatment for ADA-SCID.