serum-free thymus transplantation in digeorge anomaly

Conditions: DiGeorge Anomaly

Summary: the study purpose is to determine if thymus tissue cultured in a serum-free (sf) solution is a safe and effective treatment for atypical and typical complete digeorge anomaly. \[funding source - fda oopd\]

complete digeorge anomaly is a congenital disorder characterized by athymia. without successful treatment, patients remain immunodeficient and usually die by age 2 years. in "typical" complete digeorge subjects who have no t cells, thymus transplantation without immunosuppression has resulted in diverse t cell development and good t cell function. in "atypical" complete digeorge subjects who have no thymus, a rash, and some t cells that presumably developed extrathymically, thymus transplantation with immunosuppression has resulted in diverse t cell development and good t cell function. thus far, thymus transplantation studies have used thymus cultured in fetal bovine serum (fbs medium). this protocol's purpose is to determine whether transplanted thymus cultured in serum free medium can safely support thymopoiesis and t cell reconstitution as does fbs medium cultured thymus tissue in digeorge anomaly subjects. this protocol includes 2 arms: atypical digeorge subjects who will receive immunosuppression and thymus transplantation; and, typical complete digeorge subjects who will receive thymus transplantation without immunosuppression. serum free medium use would reduce concerns of animal product exposure including potential exposure to bovine spongiform encephalopathy(bse).

Eligibility criteria:
thymus recipients inclusion: complete digeorge anomaly diagnosis must have one of following: * congenital heart disease * hypocalcemia requiring replacement * 22q11 or 10p13 hemizygous * charge atypical arm: * must have, or have had, rash. if rash present, skin biopsy must show t cells. if rash resolved, must have \>50/cumm t cells; \& \<50/cumm naive t cells or \<5% total * pha response must be \<40000 counts per minute(cpm) on immunosuppression; or, \<75000cpm off immunosuppression. pha test must be done 2x * cd45ra+cd62l+ cd3+ t cells must be \<50/mm3; or, \<5% of total cd3. test must be done 2x typical arm: * pha response \<20 fold or \<5,000cpm * circulating cd3+cd45ra+cd62l+t cells \<50/mm3 or \<5% total t cells * 2 tests of t cells \& pha response must show similar results biological mother inclusion: -must be recipient's biological mother thymus recipient exclusion: * heart surgery \<4 weeks pre-transplant or within 3 months post-transplant * rejection by surgeon or anesthesiologist as surgical candidates * lack of sufficient muscle tissue to accept transplant * medical condition does not allow to undergo a biopsy * hiv * cmv(\>500 copies/ml blood by pcr on 2 tests) * ventilator dependence * gvhd * maternal t cells \>20% of total t cells * prior immune reconstitution attempts (e.g., bmt, prior thymus transplant) * hypoparathyroidism meeting criteria for combined thymus/parathyroid transplant \& parents desiring it * rsv or parainfluenza virus * enterovirus or adenovirus in stool biological mother exclusion: -unwillingness to sign consent or provide blood/buccal samples

Keywords: thymus transplantation digeorge anomaly athymia low t cell numbers immunoreconstitution immunodeficiency