Unrelated donor lymphocyte infusions as a treatment of immunodeficiency in complete DI George syndrome

Complete DiGeorge syndrome (DGS) is a rare congenital disorder characterized by number of developmental defects and T-cell deficiency. We present an infant with multiple anomalies (choanal and esophageal atresia, coloboma, tracheobronchomalacia, etc.), diagnosed at the age of 2 months with complete DGS (absence of T cells, no response to mitogens, absent thymus), treated with unrelated donor lymphocyte infusion (DLI). During first 7 months of age he required long-term ventilation, suffered recurrent infections, and sepsis. He had no sibling and no fully matched unrelated donor was available. At the age of 6 months the first dose of DLI (1 × 106 /kg CD3+; 2 ×105/kg CD34+) was administered to him from an unrelated donor (mismatched for B and Cw alleles) with no conditioning regimen and no graft versus host disease (GVHD) prophylaxis. Ten days after DLI, he developed severe acute GVHD (skin stage 3–4) complicated with sepsis, cardiopulmonary instability, capillary leak syndrome, and ileus. He was treated with antithymocyte globulin (rATG), cyclosporin A (CsA), and steroids with a complete resolution of GVHD. On day +36 after first DL, he was given the second DLI (0.9 × 106/kg CD3+) with no conditioning and GVHD prophylaxis consisting of continued CsA. EBV infection has appeared 4 weeks after infusion (peripheral expansion of CD8+ donor cells started), successfully treated with CsA withdrawal and rituximab. Isolated cholestatic liver GVHD manifested month after second DLI, progressed to stage 4, successfully treated with steroids, CsA, and rATG. Since day +10 after first DLI, the donor genotype due to presence of donor T cells is documented in VNTR. Response to mitogens appeared and is now comparable to healthy controls. Central memory (CD27pos, CD45RAneg) stages dominate in the peripheral blood CD4 and CD8 cells (64 to 81% and 52 to 95%, respectively), which was higher than in control. Effector memory cells are increased in CD4 subset, decreased in CD8. Naive CD4 T cells (CD45RApos, CD27pos) continued to be completely absent at all time-point measured, but naive CD8 (CD45RApos, CD27pos) were detected already at D +100 at 5% and continued raise thereafter. The patient is now 10 months after first DLI still on CsA and steroids, slowly started to gain his developmental milestones. We believe that infusions of small doses of DLI from an unrelated donor represent an adequate therapy for complete DiGeorge syndrome.