Subject characteristics, treatment, and outcomes
| PIN . | Age at entry . | Sex . | Mutation(s) . | PEG-ADA ERT . | Busulfan conditioning, mg/m2 . | CD34+ cell dose (× 106/kg) . | VCN,* copy/cell . | ADA enzyme activity,† nmol/108 cells/min . | Years of follow-up . | PEG-ADA ERT status . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MND-ADA . | GCsap M-ADA . | MND-ADA . | GCsap M-ADA . | |||||||||
| 201C | 15 y | F | c.955–959del | Continued | No | 0.7 | n.a.‡ | 0.06 | n.a.‡ | 36 | 10 | Continued |
| c.529C > A | ||||||||||||
| 202N | 6 y | F | Homozygous | Continued | No | 9.8 | 1.46 | 0.78 | 70.3 | 148.5 | 10 | Continued |
| c.632G > A | ||||||||||||
| 203N | 20 y | F | c.302G > T | Continued | No | 1.1 | Not done | Not done | 8.3 | 7.6 | 9 | Continued |
| c.872C > T | ||||||||||||
| 204C | 4 y | M | Not available | Continued | No | 1.9 | 0.48 | 0.25 | 143 | 50.3 | 9 | Continued |
| 301N | 2 y | M | c.424C > T | Withdrawn | 75 | 4.8 | Not done | Not done | 43.4 | 204.5 | 5 | Off × 5 y |
| c.976A > G | ||||||||||||
| 302C | 3 y | F | c.302G > A | Withdrawn | 75 | 1.5 | 0.106 | 0.0745 | 34.25 | 43.55 | 5 | S/P MUD HSCT§ |
| c.632G > A | ||||||||||||
| 303N | 15 mo | F | c.478 + 1G > A | Withdrawn | 75 | 1.9 | 1.2 | 13 | 7.23 | 88 | 4 | Off × 4 y |
| c.646G > A | ||||||||||||
| 304C | 9 yr | F | c.221G > T | Withdrawn | 65 | 1.6 | 0.3 | 0.14 | 5.9 | 10.5 | 3.5 | Resumed after 5 mo¶ |
| c.986C > T | ||||||||||||
| 305C | 20 mo | M | Homozygous | Withdrawn | 90 | 9.8 | 0.0565 | 0.69 | 14.28 | 85.53 | 3 | Off × 3 y |
| c.632G > A | ||||||||||||
| 306N | 22 mo | M | Homozygous | Withdrawn | 90 | 9.5 | 0.215 | 1.78 | 54.9 | 170 | 2.5 | Resumed after 5 mo¶ |
| c.955–959del | ||||||||||||
| PIN . | Age at entry . | Sex . | Mutation(s) . | PEG-ADA ERT . | Busulfan conditioning, mg/m2 . | CD34+ cell dose (× 106/kg) . | VCN,* copy/cell . | ADA enzyme activity,† nmol/108 cells/min . | Years of follow-up . | PEG-ADA ERT status . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MND-ADA . | GCsap M-ADA . | MND-ADA . | GCsap M-ADA . | |||||||||
| 201C | 15 y | F | c.955–959del | Continued | No | 0.7 | n.a.‡ | 0.06 | n.a.‡ | 36 | 10 | Continued |
| c.529C > A | ||||||||||||
| 202N | 6 y | F | Homozygous | Continued | No | 9.8 | 1.46 | 0.78 | 70.3 | 148.5 | 10 | Continued |
| c.632G > A | ||||||||||||
| 203N | 20 y | F | c.302G > T | Continued | No | 1.1 | Not done | Not done | 8.3 | 7.6 | 9 | Continued |
| c.872C > T | ||||||||||||
| 204C | 4 y | M | Not available | Continued | No | 1.9 | 0.48 | 0.25 | 143 | 50.3 | 9 | Continued |
| 301N | 2 y | M | c.424C > T | Withdrawn | 75 | 4.8 | Not done | Not done | 43.4 | 204.5 | 5 | Off × 5 y |
| c.976A > G | ||||||||||||
| 302C | 3 y | F | c.302G > A | Withdrawn | 75 | 1.5 | 0.106 | 0.0745 | 34.25 | 43.55 | 5 | S/P MUD HSCT§ |
| c.632G > A | ||||||||||||
| 303N | 15 mo | F | c.478 + 1G > A | Withdrawn | 75 | 1.9 | 1.2 | 13 | 7.23 | 88 | 4 | Off × 4 y |
| c.646G > A | ||||||||||||
| 304C | 9 yr | F | c.221G > T | Withdrawn | 65 | 1.6 | 0.3 | 0.14 | 5.9 | 10.5 | 3.5 | Resumed after 5 mo¶ |
| c.986C > T | ||||||||||||
| 305C | 20 mo | M | Homozygous | Withdrawn | 90 | 9.8 | 0.0565 | 0.69 | 14.28 | 85.53 | 3 | Off × 3 y |
| c.632G > A | ||||||||||||
| 306N | 22 mo | M | Homozygous | Withdrawn | 90 | 9.5 | 0.215 | 1.78 | 54.9 | 170 | 2.5 | Resumed after 5 mo¶ |
| c.955–959del | ||||||||||||
ADA indicates adenosine deaminase; ERT, enzyme-replacement therapy; HSCT, hematopoietic stem cell transplantation; MUD, matched unrelated donor; PEG-ADA, polyethylene glycol-conjugated adenosine deaminase; PIN, patient identification number; and VCN, vector copy number.
VCN in transduced CD34+ cells by quantitative PCR.
ADA enzyme activity in transduced CD34+ cells.
For subject 201C, only the GCsapM-ADA vector was used.
Status post-MUD HSCT 8 months after gene transfer for marrow aplasia.
Attributable to the development of infection.