Table 2.
Haploidentical HSCT and autologous gene-therapy in CGD between 2014 and 2020.
| Author*Year of report | Hoenig et al. (97) | Parta et al. (98) | Shah et al.** (99) | Reguiero-Garcia et al. (100) | Lum et al. ** (80) | Parta et al. (101) | Kohn et al. (102) |
|---|---|---|---|---|---|---|---|
| Conditioning | MAC | RTC | RTC/MAC | RTC/MAC | RTC/MAC | RTC | Gene therapy |
| (type of T-cell depletion) | Bu/Flu/TT CD34+ positive selection (in-vitro) | Bu/Flu/CY/TBI 2 Gy+post CY2 × 50 (d+3/+4) (in-vivo) | Treo/TT/Flu TCR-alpha/beta+/CD19+-depletion (in-vitro) | Treo-based +post CY 2 × 50 (d + 3/4) (in-vivo) | Treo/TT/Flu TCR-alpha/beta+/CD19+-depletion (in-vitro) | Bu/Flu/CY/TBI 2 Gy+post CY2 × 50 (d + 3/+4) (in-vivo) | Myeloablative Busulfan |
| TDM | No | No | No | No | Yes | Yes | |
| Target Bu (total dose mg/kg) Achieved Cauc mg/L × h | No (17.6) | No (10.4) 37 | No | No | No | No (10.4) 30–52 | Target 70–75 |
| Ped/Adult Age (yrs) | Ped (6) | Ped (14) | Ped (3) | Ped (ND) | ND ND | Mixed (14–26) | Mixed (2–27) |
| Patients n= | 1 | 1 | 2 | 1 | 4 | 7 | 9 |
| X-linked CGD % | 100 | 100 | 50 | 100 | ND | 71 | 100 |
| Colitis % | 0 | 100 | 50 | ND | ND | 86 | 11 |
| PGLD % | 0 | 0 | 0 | ND | ND | 0 | 22 |
| Lung infection % | 100 | 100 | 50 | ND | ND | 43 | 33 |
| Liver abscess % | 0 | 0 | 0 | ND | ND | 0 | 11 |
| McLeod % | 0 | 9 | 0 | ND | ND | ND | 0 |
| Donor | |||||||
| Type of transplant | 1 haplo | 1 haplo | 2 haplo | 1 haplo | 4 haplo | 7 haplo | 9 autologous |
| Father | 1 | 1 | 2 | ND | ND | 5 (1 brother) | NA |
| Mother | 0 | 0 | 0 | ND | ND | 1 (10/10 phenoident.) | |
| Source | PBSC | PBSC | PBSC | ND | PBSC | PBSC | PBSC |
| Outcome | |||||||
| Med. FU (mo.) | 48 | 9 | 47 | ? | ND | 36 | ND (12–36) |
| OS% | 100 | 100 | 100 | 100 | 100 | 71 | 78 |
| EFS% | 100 | 100 | 100 | 100 | 100 | 71 | 66 |
| Myeloid DC% (n=) | 90 (1) | 100 (1) | 100 (2) | ND | 100 (4) | 96–100 (7) | 12–46 (7)*** |
| DLI/SCB | 0 | 0 | 0 | ND | 0 | 0 | NA |
| Re-HSCT | 0 | 0 | 0 | ND | 0 | 0 | ND |
| Graft failure % | 0 | 0 | 0 | ND | 0 | 0 | 22 |
| Acute GVHD III-IV % | 0 | 0 | 0 | ND | 0 | 43 | NA |
| Chronic GvHD % | 0 | 0 | 0 | ND | 0 | 29 | NA |
| Lethal infections (n=) | 0 | 0 | 0 | 0 | 0 | 2 | Pneumonitis (1) ICH (1) |
| De-novo autoimmunity % Type (n=) | ND | ND | ND | ND | ND | ND | ND |
| Reported fertility (n=) | ND | ND | ND | ND | ND | ND | ND |
Bu, Busulfan; cAUC, cumulative area under the curve; CY, cyclophosphamide; DC, donor chimerism; DLI, donor lymphocyte infusion; EFS, event free survival; Flu, fludarabine; FU, follow-up; GVHD, chronic graft-versus-host disease; haplo, haploidentical family donor; ICH, intracranial hemorrhage; PGLD, progressive granulomatous lung disease; MAC, myeloablative conditioning; NA, not applicable; ND, not determined; OS, overall survival; PGLD, progressive granulomatous lung disease; rATG, rabbit Anti T-cell globulin; RIC, reduced intensity conditioning; RTC, reduced toxicity conditioning; SCB, stem cell boost; TDM, therapeutic drug monitoring; Treo, treosulfan; TT, thiotepa.
Literature citation see main manuscript.
Presumably patients of the same UK cohort.
Percentage of functional neutrophils.