Newborns with genetic variants in interleukin 7 receptor (IL7R) resulting in severe combined immunodeficiency (SCID) are commonly identified after an abnormal newborn screen. These patients experience profound T cell lymphopenia with varied humoral findings and are at risk for infection prior to definitive therapy. Definitive therapy includes hematopoietic stem cell transplant (HCT) and can result in immune reconstitution.
Retrospective chart review of four patients with IL7R SCID who were diagnosed through newborn screening in Maryland, Virginia, or Washington, D.C., and received HCT at Children’s National Hospital.
All four patients were found when the newborn screening identified abnormal T cell receptor excision circle (TREC) values and were evaluated by immunology between 8-13 days of life. Each patient had markedly reduced CD3+ T cells at presentation (CD3+ 5-23 cells/mcL), variable B cells (CD19+ 354 cell/mcL–1,948 cells/mcL), and natural killer (NK) cell counts (CD16/56+ 288 cells/mcL–946 cells/mcL). Humoral profiles varied, with all patients exhibiting normal immunoglobulin G (IgG) and M (IgM). Two patients had absent immunoglobulin A (IgA) levels. Antifungal prophylaxis was initiated between days of life (DOL) 14-41. Pneumocystis jirovecii pneumonia (PJP) prophylaxis was initiated between DOL 30-41, and immunoglobulin replacement was initiated between DOL 30-53. Maternal CMV IgG was positive in three mothers. All mothers who had positive CMV IgG were asked to stop breastfeeding. One mother with detectable CMV stopped breastfeeding. All patients experienced pre-transplant infections ranging between upper respiratory infections, including parainfluenza, rhino/enterovirus, and respiratory syncytial virus (RSV), and fungal infections, including candidal intertrigo of axilla and pityrosporum folliculitis. Transplant strategies encompassed haploidentical peripheral blood HCT (3 patients) and matched sibling donor marrow HCT (1 patient). One patient received anti-CD117 monoclonal antibody conditioning with graft failure necessitating subsequent HCT. Three patients received a preparative regime of busulfan, fludarabine, and rabbit antithymocyte globulin (rATG), and one patient received busulfan and fludarabine preparative regime. Post-transplant complications included CMV disease (retinitis, pneumonia, and enteric involvement) requiring virus-specific T cell therapy, hypertension, transaminitis, norovirus, and poor oral intake. All four patients demonstrated full donor T cell chimerism and mixed myeloid chimerism. Post-transplant immune assessments showed T cell reconstitution, improved lymphocyte proliferation to mitogens, and appropriate immunoglobulin values. Vaccine responses were protective to diphtheria, tetanus, and pneumococcal serotypes, and all patients were off chronic IgG replacement between 106–244 days after transplant.
In this cohort of four patients with IL7R SCID, newborn screening was essential for diagnosis and implementation of prophylactic treatment. Despite early intervention, patients with IL7R SCID may still experience pre-transplant complications such as upper respiratory infections or fungal infections. Early definitive therapy is essential and can lead to immune reconstitution.
