Table 1.
Clinical, genetics, and biological characteristics of ADA-SCID patients who developed lymphoma (review of the published cases).
| Reference | ADA mutation | PEG-ADA | HSCT for ADA-SCID | Lymphoma type | Organs involved | EBV related | Age at onset | Treatments for lymphoma | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Kapoor (7) | nk | No | Second haplo T depleted, no conditioning, poor engraftment (only T cells), and donor EBV positive | B cell of host origin, 85% k chain—50% delta chain—90% μ chain | Liver, spleen, CNS, gut, lung, and BM | Yes | 1 year after II HSCT | nk | Dead 1 week after lymphoma onset |
| Ratech et al. (8) | nk | Yes | No | Diffuse large cell immunoblastic plasmacytoid type NHL (MALT). Monoclonal IgA lambda | Gut, spleen, nodes, liver, lung, kidney, meninges, and adrenal gland | nk | nk | nk | Died at 4 years |
| Hirschhorn et al. (9) | E217K; exon 1–5 deletion | No | Haplo-HSCT | nk | nk | nk | 1.5 years after HSCT | 2 HSCT (haplo) | Dead |
| Hershfield (10) | nka | Yes for 13 years | No | Hodgkin lymphoma | nk | Yes | 13 years after starting PEG-ADA | HSCT (CB) | Died at 16 years |
| Hershfield (10) | nk | Yes for 10 years | No | nk | Pulmonary nodule | Yes | 8 years after starting PEG-ADA | Rituximab; HSCT (MUD) at 10 years | Died of viral disease 1 month after HSCT |
| Kaufman et al. (11) | A83D; Exon5 splice donor site c.573 + 1G>A | Yes for 10 years | No | B large cell type. Immunoblastic and plasmacytoid features. BCL6 neg. Deletion in 1p36, 19q13, and 10q23 | CNS | Yes | 10 years | DXM + phenytoin; COP + APO + 6-MP; MTX | Dead |
| Husain et al. (12) | Q3X (h) | Yes for 14 years | No | Burkitt’s lymphoma. CD20 and CD79a positive Aberrant co-expression T marker CD43 | Right iliac-ischial bone | No | 15 years | Chemotherapy not specified | Complete remission 20 months after diagnosis |
| Genel (13) | W272X (h) | Yes for 3 years | No | Diffuse large B cell lymphoma NHL | Multiple pulmonary nodules and splenic mass | nk | 3 years | Chemotherapy (BFM 2004 protocol) | Dead |
| Current patient | 462delG (h) | Yes for 17 years | No (infusion of gene corrected peripheral blood lymphocytes) | Plasmablastic B-cell lymphoma with plasmocytoid features. CD138, MUM-1, kappa light chain monoclonal, CD20 partially positive | Nodes, lungs, periocular, spleen, and BM | Yes | 18 years | Rituximab; APO; and cyclophosphamide + dexamethasone | Dead |
HSCT, hematopoietic stem cell transplantation; EBV, Epstein–Barr virus; nk, not known; NHL, non-Hodgkin lymphoma; h, homozygous; Haplo, haploidentical; CB, cord blood; MUD, matched unrelated donor; CNS, central nervous system; BM, bone marrow; COP, cyclophosphamide, vincristine, and prednisone; APO, doxorubicin, vincristine, and prednisone; 6-MP, 6-mercaptopurine; ADA-SCID, adenosine deaminase-deficient severe combined immunodeficiency disease.
aThis patient is the brother of the one described in Hirschhorn et al. (9).