Table 1.
Characteristics and treatment of the three WAS patients.
| Patient 1 | Patient 2 | Patient 3 | |
|---|---|---|---|
| Infectious manifestations | Recurrent ENT | Pneumonias, Colitis arthritis/cellulitis, URTI, UTI | Pneumonia with respiratory distress, URTI, otitis |
| Pathogens | VZV, CMV, HSV, EBV | CMV, HSV6, candida | Pneumocystis jirovecii, CMV |
| Thrombocytopenia manifestations | Skin petechiae | Skin petechiae, GI bleeding | Skin petechiae, GI bleeding, epistaxis |
| Eczema | Moderate-severe | Moderate-severe | Severe |
| Other | Developmental disorder, allergy | Failure to thrive, ⇑Inflammatory indexes/vasculitis, hepatosplenomegaly | GE reflux/food adversion (fed by naso-gastric tube), allergy |
| WAS mutation | Exon 10: C>T 995 (R321X) | IVS10del11nt | 37C>T (R13X) |
| WASP expression | <5% | <5% | <5% |
| Zhu score | 3 | 4 | 4 |
| Age at treatment (y) | 5.9 | 1.6 | 1.1 |
| Infused CD34+ cells (×106/kg) | 3.66 (BM) + 5.25 (MPB) | 14.1 | 10.2 |
| Vector copies/genome | 1.9 (BM)−1.4 (MPB) | 2.4 | 2.8 |
| Transduction efficiency (CFC) | 92% (BM)−88% (MPB) | 97% | 100% |
| Follow-up (mo) | 32 | 23 | 20 |
| Current clinical conditions | A&W No eczema No major bleeding/petechiae Off IVIG |
A&W No eczema No major bleeding/petechiae |
A&W No eczema No major bleeding/petechiae |
ENT, ear nose throat, URTI; upper respiratory tract infection; UTI, urinary tract infection; GI, gastrointestinal. GE, gastroesophageal. IVIG, intravenous immunoglobulins. WASP expression analysis was performed on PB lymphocytes by FACS. Patient 1 also received G-CSF mobilized peripheral blood (MPB)-derived CD34+ cells, previously collected as back-up, to achieve the target HSPC dose. F.U., follow-up. A&W, alive and well. Y, years. Mo, months.