Table 1.
Major HSCT studies with HLA-matched donor transplants in CGD between 2001 and 2019 (n >5 patients).
| Author*Year of report | Horwitz et al. (66) | Seger et al. (67) | Schuetz et al. (68) | Soncini et al. (69) | Gozdzik et al. (70) | Martinez** et al. (71) | Tewari et al. (72) | Ahlin et al. (73) | Gungor et al. (63) | Morillo-Gutierrezet al. (74) | Khandelwal et al. (75) | Parta et al. (64) | Osumi et al. (76) | Yanir** et al. (77) | Fox et al. (78) | Arnold et al. (79) | Lum et al. (80) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Conditioning | RIC Flu/CY + rATG | MAC (most) Bu/CY ±TNI/TT /Mel /rATG | MAC (most) Bu/Cy ± TBI, Mel, RIT ± rATG | MAC (most) Bu/Cy +Camp. | MAC (most) Bu/Cy or Flu/Mel + rATG | MAC Bu/Cy + Flu + Campath | MAC Bu/Cy + Flu + −2 Gy TBI + eATG | RIC and RTC/MAC1. Bu/CY2. Bu/Flu 3. Treo/Flu ± rATG | RIC Flu/low Bu + rATG or Campath | RTC Flu/Treo/ or Cy or TBI ± rabbit ATG or Camp. | RIC and RTC/MAC Flu/Mel + Camp. Or Bu/CY + rATG | RTC Bu (10 mg/kg)/TBI 3 Gy, +Camp. | RTC Flu/Bu/TBI 3 Gy + ATG | MAC Bu/Flu/CY + Ara C, + Camp. | RIC 1. Flu/Bu +Camp. or rATG (1) 2. Flu/Mel +Camp. (2) | MAC Bu/Flu +ATG (+TT) | MAC RIC/RTC Mixed |
| TDM | No | No | No | No | No | No | No | No | Yes | No | Yes | No | Yes | Yes | Yes | Yes | No |
| Target Bu cAUC Achieved cAUC mg /Lx h | No | No | No | No | No | No | No | No | Yes 45–65 30–65 | No | Yes 60–70 59–66 | No 19–88 | Yes 45–65 39–52 | No 60–80 | No 44–63 | No 59–98 | No |
| Ped/Adult Age (yrs) | Mixed 5–36 | Mixed 3–39 | Mixed 4–20 | Mainly Ped. 1–21 | Ped. 2–13 | Ped 1–13 | Ped. 0.7–11.7 | Mixed 1–35 | Mixed 1–39 | Ped. 0.4–19 | Mainly Ped. 0.45–20.17 | Mixed 4–32 | Ped. 2–18 | Mixed 0.5–30 | Adult 17–28 | Ped. 1–13 | Ped. 0.6–18 |
| Patients n= | 10 | 27 | 12 | 20 | 6 | 11 | 12 | 14 | 56 | 70 | 18 | 40 | 6 | 24 (11**) | 11 | 7 | 55 |
| X-linked CGD % | 80 | 85 | 92 | 95 | 83 | 82 | 67 | 71 | 61 | 80 | 44 | 85 | 83 | 88 | 64 | 86 | 82 |
| Colitis% | ND | 7 | 0 | 50 | 0 | 9 | 30 | 14 | 34 | 50 | 11 | 12.5 (?) | 67 | 0 | 55 | 43 | 91 |
| PGLD% | ND | 26 | 58 | 25 | 67 | 27 | ND | ND | 14 | 21 | 11 | 0 | 0 | 4 | 0 | 0 | 7 |
| Lung infection % | ND | 26 | 83 | 25 | 33 | 55 | 17 | 43 | 27 | 17 | 0 | 20 | 0 | 25 | 27 | 14 | ? |
| Liver abscess % | ND | 0 | 40 | 15 | 0 | 9 | 8 | 7 | 2 | 0 | 0 | 2.5 | 0 | 0 | 0 | 14 | ? |
| McLeod n= | ND | ND | 2 | ND | ND | ND | ND | 2 | 1 | 1 | 0 | 2 | 0 | 0 | 1 | 0 | ? |
| Donor n= | |||||||||||||||||
| MSD/MFD n= (carrier n=) | 10 | 25 (5) | 3 | 10 (1) | 2 | 4 | 6 | 5 (2) | 21 | 13 | 3 | 6 | 0 | 6 | 3 | 1 | 20 |
| MUD 10/10 | 0 | 2 | 9 | 10 | 3 | 7 | 0 | 7 | 25 | 44 | 15 | 33 | 3 | 16 | 6 (10/10 MUD) | 7 | 31 |
| MUD 9/10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 10 | 11 | 0 | 1 | 3 | 4 | 2 (9/10 MUD) | 0 | ND |
| MMUD 8/10 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 haplo | 0 | 0 | 0 | 0 | 8 | 0 | 4 haplo |
| UCB 4-6/6 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 4 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 2 |
| Source n= | 0 BM | 24 BM | 9 BM | 15 BM | 6 BM | 11 | 5 BM | 11 BM | 45 BM | 36 BM | 16 BM | 5 BM | 6 BM | ND BM | 4 PBSC | 6 BM | 53 BM |
| 10 PBSC | 3 PBSC | 3 PBSC | 3 PBSC | 0 PBSC | 0 PBSC | 0 PBSC | 3 PBSC | 11 PBSC | 33 PBSC | 1 PBSC | 35 PBSC | 0 PBSC | ND PBSC | 7 BM | 2 PBSC | 23 PBSC | |
| 0 CB | 0 CB | 0 CB | 2 CB | 0 CB | 0 CB | 9 CB | 4 CB | 0 CB | 1 CB | 1 CB | 0 CB | 0 CB | 0 CB | 0 CB | 0 CB | 2 CB | |
| Outcome | |||||||||||||||||
| Med. FU in months | 17 | 24 | 53 | 61 | 20 | 48 | 70.5 | 92 | 21 | 34 | 20 (in RIC) 60 (in RTC/MAC) | 41 | 12 | 48 | 33 | 32 | 78 |
| OS % | 70 | 85 | 75 | 90 | 100 | 100 | 100 | 93 | 96 | 90.5 | 83 | 82.5 | 100 | 91 | 81.8 | 100 | 89 |
| EFS % | 60 | 81 | 67 | 90 | 83 | 100 | 100 | 79 | 91 | 81 | 50 | 80 | 83 | 83 | 90.9 | 90 | 77 |
| Myeloid DC% n = pat. | 6 (full) 2 (mix.) | 22 (full) | 11 (full) | 14 (full) | 100% | 9 (full) 2 (mix.) | 15 (>90%) | 12 (>90%) 1 (60%) | 52 (>90%) | 51 (>95%) 1 (<90%) 3 (39–74%) | 14 (>95%) 1 (50%) 2 (11–40%) | 27 (>97%) 3 (>70%) 1 (<50%) | 5 (>95%) 1 (0%) | 22 (full) 2 (mixed) | 4 (100 %) 7 (mixed) | 7 (full) | 43 (Med. 92%) |
| DLI/SCB | 9/0 | 2/0 | 0/0 | 0/0 | 1/0 | 0/0 | 0/0 | 3/0 | 0/0 | 4/0 | 1/2 | 0/6 | 0/0 | 0/0 | 0/0 | 0/0 | 0/3 |
| Re-HSCT | 0 | 0 | 1 | 1 | 1 | 0 | 3 | 3 | 3 | 5 | 0 | 3 | 1 | 2 | 0 | 1 | 4 |
| DSF after re-HSCT% | NA | NA | 0 | 100 | 100 | NA | 100 | 67 | 67 | 80 | NA | 0 | ND | 100 | NA | 100 | 100 |
| Graft failure % (n=) | 20 (2) | 7 (2) | 17 (2) | 5 (1) | 16 (1) | 0 (0) | 25 (3) | 14 (2) | 5 (3) | 12 (8) | 50 (2) | 22 (9) | 17 (1) | 8 (2) | 0 | 15 (1) | 7 (4) |
| aGVHD III-IV % (n=) | 10 (1) | 15 (4) | 0 (0) | 10 (2) | 17 (1) | 0 (0) | 8 (1) | 7 (1) | 4 (2) | 12 (8) | 28% (5) | 15% (6) | 17% (1) | 0% (0) | 1 | 15 (1) | 9 (5) |
| chronic GVHD % (n=) | 20 (2) | 11 (3) | 8 (1) | 10 (2) | 17 (1) | 0 (0) | 33 (4) | 0 (0) | 7 (4) | 13 (9) | 22 (4) | 12.5 (5) | 17 (1) | 0 (0) | 3 (1) | 0 (0) | 0 (0) |
| Lethal infections (n=) | Bact. (1) Fung. (1) | Fung. (2) Pre-exist. | BK (1) CNS (1) ARDS (1) | Fung. (2) Pre-exist. | (0) | (0) | (0) | Fung. (1) Pre-exist. | PTLD (1) | Bact. (1), ADV (2), FLU (1) | Fung. (1) | Bact. (2), Fung. (1) Pre-exist. | Not specified (2) | (0) | ND | (0) | PTLD (1) |
| De-novo autoimmunity % Type (n=) | ND | ND | ND | 11 Thyroid (2) | ND | 18 Thyroid (1) AIHA (1) | 25 ITP (3) | 7 AIN (1) | 4 AIHA (2) | 5 AIHA (2) GBS (1) | ND | 2.5 AIHA/ITP (1) | ND | 50 AIHA/ITP (6) Thyroid (6) GB (2) | ND | 14 AIHA (1) | 12 AIHA (3) Thyroid (2) DM (1) |
| Reported fertility (n=) | ND | ND | ND | ND | ND | ND | ND | ND | Fatherhood. (2) | ND | ND | ND | ND | ND | Fatherh. (1) Viable sperm (2) | ND | ND |
ADV, adenovirus; aGVHD, acute Graft-vs.-host disease; AIHA, autoimmune hemolytic anemia; AIN, autoimmune neutropenia; ARDS, acute respiratory distress syndrome; Bact, bacteria; Bu, Busulfan; Camp, Campath IH/Alemtuzumab; chronic GVHD, chronic graft-vs.-host disease; CY, cyclophosphamide; DC, donor chimerism; DFS, disease-free survival; DLI, donor lymphocyte infusion; DM, diabetes mellitus, eATG, equine Anti T-cell globulin; EFS, event free survival; Fatherh., fatherhood; Flu, fludarabine; FU, follow-up; Fung, fungi; GB, Guillain-Barré-Syndrome; ICH, intracranial hemorrhage; ITP, immune thrombocytopenia; LD, lung disease; MAC, myeloablative conditioning; med, median; Mel, melphalan; MSD, matched family donor; MFD, matched family donor; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; NA, not applicable; ND, not done; OS, overall survival; PGLD, progressive granulomatous lung disease; SCB, stem cell boost; TDM, therapeutic drug monitoring; rATG, rabbit Anti T-cell/thymocyte globulin; RIC, reduced intensity conditioning; RTC, reduced toxicity conditioning; RIT, radioimmune therapy; SCB, stem cell boost; TDM, therapeutic drug monitoring; TBI, total body irradiation; TNI, total nodal irradiation; Treo, treosulfan; TT, thiotepa; UCB, unrelated cord blood.
Literature citation see in main manuscript.
11 patients from Martinez were reanalyzed with a longer follow-up in Yanir‘s investigation.