Table 3.
Transplant outcomes from published studies using TCD and TCR platforms for haplo-HSCT for SCD.
| Author | Graft Source | Conditioning Regimen | N | OS | GvHD | Engraftment (%) | Complications |
|---|---|---|---|---|---|---|---|
| Gaziev et al. [51] T-cell receptor alpha/beta+ CD19 depletion |
PBSC | Hydroxyurea and azathioprine with fludarabine pre-conditioning ATG, busulfan, thiotepa, and cyclophosphamide GvHD prophylaxis—cyclosporine and methylprednisolone or cyclosporine and MMF |
3 sickle cell disease and 11 thalassemia | 84% at 5 years | 36% (5/14) acute GvHD 21% (3/14) chronic GvHD |
86% | 4 developed auto-immune disorders Infections Reactivation of CMV and EBV BK virus Adenovirus Bacterial infections with Gram-positive and Gram-negative sepsis Fungal |
| Gilman et al. [53] CD34+ selection |
PBSC | Reduced intensity ATG, melphalan, thiotepa, fludarabine GvHD prophylaxis—none |
8 | 88% (7/8) at over a range of 6–60 months | 25% (2/8) grades II–IV acute GvHD 12.5% (1/8) moderate–severe chronic GvHD |
100% (8/8) | 2 with engraftment syndrome 2 with posterior reversible encephalopathy syndrome 88% (7/8) alive and without SCD 13% (1/8) died from disseminated aspergillosis All survivors in school and/or employed Infections 4 with EBV reactivation (2 with PTLD), 1 with CMV enteritis, 6 with HHV-6 reactivation |
| Foell et al. [52] CD3+ and CD19+ depletion |
PBSC | Myeloablative ATG, fludarabine, thiotepa, and treosulfan GvHD prophylaxis—cyclosporine and MMF |
9 | 89% (8/9) at over a range of 6–42 months (median 26 months) | 56% (5/9) grades I–II acute GvHD 11% (1/9) chronic moderate–severe GvHD |
100% (9/9) | Grades 1–2 mucositis, diarrhea, limited pain crises with hemiplegia, 1 with neuromuscular spasms with cranial nerve V and VII transient impairment 89% (8/9) alive and without sickle-cell-disease-related symptoms 11% (1/9) died from CMV-pneumonitis Infections 3 with CMV reactivation, 1 with CMV pneumonitis Reactivation of EBV, adenovirus, HHV-6, and BK virus |
| Bolanos-Meade et al. [6] PTCy |
G-BM (3), BM (11) | Non-myeloablative ATG (12 patients), fludarabine, cyclophosphamide, and total body irradiation GvHD prophylaxis—PTCy, FK, sirolimus, and MMF |
14 (age range 15–42 years) | 100% (14/14) at 7.5–66 months | 0% (0/14) acute GvHD 0% (0/14) chronic GvHD |
57% (8/14) | 50% (7/14) alive and without sickle-cell-related symptoms No new strokes, acute chest syndrome, or priapism Infections 3 with CMV reactivation, 1 with EBV reactivation, and 1 with RSV upper respiratory infection and mycobacterium lung infection |
| Fitzhugh et al. [7] PTCy |
PBSC | Non-myeloablative alemtuzumab, total body irradiation GvHD prophylaxis—PTCy, sirolimus |
12 (age range 20–56 years) | 92% (11/12) | 8% (1/8) acute GvHD 8% (1/8) chronic GvHD |
70% | No SCD-related issues and no sinusoidal obstruction syndrome 2 patients with graft rejection developed high-grade myelodysplastic syndrome with fibrosis 1 patient with pulmonary hypertension and heart failure (died) 1 died from infection post-surgery 50% (6/12) alive and without sickle-cell-disease-associated symptoms Infectious 4 with CMV reactivation, 1 with CMV colitis, 1 with disseminated adenovirus, 3 maintained chronic EBV viremia, 1 with EBV-PTLD, 3 were treated for presumed fungal pulmonary nodules, and 15 with bacteremia |
| De la Fuente et al. [11] PTCy |
BM | Non-myeloablative ATG, fludarabine, cyclophosphamide, total body irradiation (all), and thiotepa (15 patients) GvHD prophylaxis—PTCy, MMF, sirolimus |
18 (age range 12.1–26 years) | 100% (16/16) | 13% (2/16) grades III–IV acute GvHD 6% (1/16) limited chronic GvHD |
83% (15/18) | 1 case of sinusoidal obstruction syndrome 2 with posterior reversible encephalopathy syndrome 1 new infarct (patient who did not engraft) Suspected MMF induced gastritis, ulcer with bleeding, and typhlitis Infections 6 with EBV reactivation (no PTLD), 3 with CMV reactivation, 1 with adenovirus respiratory infection, 1 with BK cystitis, 2 cases of oral HSV infection, 2 with HHV-6 viremia (1 with HHV-6 encephalopathy) |
Legend: HLA, human leukocyte antigen; RIC, reduced intensity conditioning; PBSC, peripheral blood stem cell; BM, bone marrow; ATG, anti-thymocyte globulin; G-BM, granulocyte colony-stimulating factor primed bone marrow; MMF, mycophenolate mofetil; PTIS, pre-transplant immune suppression; PTLD, post-transplant lymphoproliferative disorder; PTCy, post-transplant cyclophosphamide; GvHD, graft-versus-host disease; OS, overall survival; EFS, event-free survival; CMV, cytomegalovirus; EBV, Epstein–Barr virus.