Clinical Course and Outcome Predictors of Critically Ill Infants With Complete DiGeorge Anomaly Following Thymus Transplantation

Abstract

Objective To identify risk factors for pediatric intensive care unit (PICU) admission and mortality of infants with complete DiGeorge anomaly treated with thymus transplantation. We hypothesized that age at transplantation and presence of congenital heart disease (CHD) would be risk factors for emergent PICU admission, and these factors plus development of septicemia would increase morbidity and mortality. Design Retrospective review Setting Academic medical-surgical PICU Patients All infants with complete DiGeorge anomaly treated with thymus transplantation between January 1, 1993 and July 1, 2010 Interventions None Measurements and Main Results Seventy one infants with complete DiGeorge anomaly were consented for thymus transplantation, and 59 were transplanted. Median age at transplantation was 5.0 (range: 1.1 – 22.1) months. After transplantation, 12/59 infants (20%) required 25 emergent PICU admissions. Seven of 12 (58%) infants survived to PICU discharge with six surviving six months post-transplantation. Forty two of 59 (71%) infants transplanted had CHD, and 9/12 (75%) who were admitted to the PICU had CHD. In 15/25 admissions (60%), intubation and mechanical ventilation were necessary. There was no difference between median ventilation-free days between infants with and without CHD (33 vs. 23 days, p = 0.544). There was also no correlation between ventilation-free days and age of transplantation (R0.17, p=0.423). Age at transplantation and presence of CHD were not associated with risk for PICU admission (OR: 0.95, 95%CI: 0.78 – 1.15 and OR: 1.27, 95%CI: 0.30 – 5.49, respectively) or PICU mortality (OR: 0.98, 95%CI: 0.73 – 1.31 and OR: 0.40, 95%CI: 0.15 – 1.07, respectively). Conclusions Most transplanted infants did not require emergent PICU admission. Age at transplantation and presence of CHD were not associated with PICU admission or mortality.

Newborn screening for severe combined immunodeficiency and T‐cell lymphopenia

“…Over 90% of these had partial DiGeorge syndrome, in which T cell numbers rose over time and T cell function was judged by their immunology providers to be adequate. However, four infants with complete DiGeorge syndrome, having persistently fewer than 300 T cells per μL and/or absent naive helper T cells, received thymus transplantation therapy in an experimental protocol at Duke University, Durham, NC, three of whom have survived for at least 2 years . Trisomy 21 accounted for eight (11%) infants with syndromes; TCL resolved in three other cases of partial DiGeorge syndrome, three died of nonimmune complications, and two were lost to follow‐up.…”

“…Based on our observed genotype frequencies for SCID (Figure ), around half of all infants with SCID may be eligible for GT in the near future. Experimental thymus transplantation has also been successful in selected cases of DiGeorge thymic insufficiency, but is not widely available …”

“…Experimental thymus transplantation has also been successful in selected cases of DiGeorge thymic insufficiency, but is not widely available. [44][45][46] Integrating Given its high degree of specificity, the TREC test for SCID has not generated excessive anxiety on the part of families or negative feedback from primary providers. Communications between screening program staff and immunologists, as well as follow-up lymphocyte phenotyping within the NBS program have assured that infants with positive tests have a prompt, consistent approach to definitive diagnosis.…”

The immune system in infants: Relevance to xenotransplantation

“…Thymic tissue allotransplantation is already being performed on babies born with DiGeorge syndrome, with good outcomes (around 70% survival), but with some autoimmune complications. [134][135][136][137][138][139][140][141] This is a relatively simple and non-invasive technique as the thymic tissue is injected into the quadriceps muscles of the recipient. 134 In a xenotransplantation model, Lee et al performed thymus transplantation from pig-to-mouse to induce tolerance and demonstrated that specific T-cell tolerance could be achieved.…”

“…Thymic tissue allotransplantation is already being performed on babies born with DiGeorge syndrome, with good outcomes (around 70% survival), but with some autoimmune complications 134‐141 . This is a relatively simple and non‐invasive technique as the thymic tissue is injected into the quadriceps muscles of the recipient 134 …”