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

Abstract

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.

Keywords: adenosine deaminase-deficient severe combined immunodeficiency disease; gene therapy; gene therapy for rare diseases; lymphoma; plasmablastic lymphoma; primary immunodeficiency; review of literature.

Figure 1

Total body positron emission tomography (PET)–computed tomography (CT). (A) Diffuse lymph nodes involvement in PET. (B) Lymphoma lung interstitial reticular thickening in CT scan. (C) Axillary and mediastinum enlargement lymph nodes in CT scan. (D) Neoplastic involvement of neck nodes and palatine tonsils in CT scan.

Figure 2

Plasmablastic lymphoma accompanied by areas of necrosis. (A) Giemsa stain highlights nuclear features of neoplastic cells, with particular reference to central, single prominent nucleolus (40×); (B) in situ hybridization for Epstein–Barr virus shows positive nuclear signal in neoplastic lymphocytes.