Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies
Abstract
:1. Allogeneic Hematopoietic Stem Cell Transplantation Landscape
2. Role of Manipulated Donor-T Lymphocytes to Enhance Immune Reconstitution
Patients/ Primary Disease/Age at HSCT Median (Range), Years | HSCT Protocol | CD34+ Cell Dose Median (Range) | Memory T Cells (CD45RA−/CD45RO+) Dose Median (Range) | Timing and n° of Infusion after HSCT Median (Range), Days | Immunological Reconstitution Time, Median (Range) Days | Clinical Outcome and Side Effects after Memory T Cells Infusion | Reference |
---|---|---|---|---|---|---|---|
N = 17, hematological malignancies, 7.7 (0.6–20.3) years | Haploidentical CD34+ selected | 17.8 (3.6–67.5) × 106/kg | 121.8 (23.6–528.4) × 106/kg | 1 infusion at day +1 |
|
| [28] |
N = 8, relapsed or refractory solid tumors, 10 (9–15.2) years | Haploidentical CD34+ selected | 10.96 (2.44–34.60) × 106/kg | 99.21 (8.56–241.53) × 106/kg | 1 infusion at day +1 |
|
| [29] |
N = 53, N = 36 hematological malignant, N = 17 hematological non-malignant, 9.4 (1–21) years | TCR alpha/beta and CD19 depleted grafts (N = 25, haploidentical; N = 28, MUD). | 8.6 (3.2–23) × 106/kg, Residual: TCR αβ+ 12.8 × 103/kg (0.4–331) | 25 × 103/kg (haploidentical) 100 × 103/kg cells (MUD) | 3 infusions of escalating doses (monthly): 25, 50 and 100 × 103/kg (haploidentical) 100, 200 and 300 × 103/kg (MUD) | Not defined |
| [31] |
N = 50 high-risk hematological malignancies, 8.1 (0.6–20.8) years | Haploidentical CD34+ selected | 16.7 (2.95–67.55) × 106/kg | 75.85 (16.1–528.6) × 106/kg | 1 infusion at day +1 |
|
| [32] |
N = 16 hematological malignancies, 54 (30–68) years | HLA-identical family donor 8/8 HLA-MUD | Not defined | 1 × 106/kg, 5 × 106/kg, 1 × 107/kg, 5 × 107/kg, 1 × 108/kg. | Dose escalation | Not defined |
| [33] |
N = 19 hematological malignancies, 62 (24–72) years | Haploidentical CD34+ | Not defined | 5 × 105/kg, 1 × 106/kg, 5 × 106/kg, | Dose escalation (4–6 weeks apart) from day +55 (46–63); |
|
| [34] |
N = 76 hematological malignancies, 8.6 (0.5–18) years | TCR alpha/beta and CD19 depleted grafts | 9 (4–14) × 106/kg, Residual: TCR αβ+ 28 × 103/kg (0.9–361) | 25 × 103/kg 50 × 103/kg | 1 infusion at day 0; Additional infusion at days: +30, +60, +90, +120 |
|
| [35] |
3. Management of Post-Transplant Viral Infections with T Lymphocytes
3.1. Role of Memory T-Lymphocytes CD45RA−/CD45RO+ to Protect against Viral Infections
3.2. Virus-Specific T Lymphocytes vs. T-Memory Lymphocytes CD45RA-/CD45RO+ to Control Symptomatic Viremia and Aspergillosis
Patients Median (Range), Years | VST Specificity | VST Doses Median | Time/Type of VST Infusion after HSCT Median (Range), Days | VST Clinical Response Only for Therapeutic Infusion: R: Responder PR: Partial Responder | Clinical Outcome and Side Effects after VST Infusion | Reference |
---|---|---|---|---|---|---|
N = 23, age not specified | CMV | 0.1–1 × 105 cell dose/kg | Pre-emptive/prophylactic infusion: 4–130 (median 36) days | Not defined |
| [58] |
N = 18, age not specified | CMV | 1 × 104 cell dose/kg | N = 11, pre-emptive infusion: 28 (25.5–31) days N = 7, prophylactic infusion: 41 (41–41.5) days | Not defined |
| [47] |
N = 18, 18 (7.5–40.7) years | CMV | 21.3 × 103 cell dose/kg | Therapeutic infusion: 106.5 (65.5–153.5) days | R: 83.4% (15 of 18) |
| [59] |
N = 9, 8 (6–10) years | ADV | 1.2–50 × 103 cell dose/kg | Therapeutic infusion: 77 (62–97) days | R: 55.5% (5 of 9) |
| [49] |
N = 5 | ADV | 1.5 × 103 cell dose/kg | Therapeutic infusion: 28 (13–61) days | R: 90% (4 of 5) |
| [60] |
N = 27, 12.15 (0.96–43.3) years | ADV | 1.5 × 106 cell dose/kg | Therapeutic infusion: days not defined | R: 54% (15 of 27) PR: 27% (8 of 27) |
| [61] |
N = 6, 30 (24–42) years | EBV | 7.3 × 104 cell dose/kg | Therapeutic infusion (positive PTLD): days not defined | R: 50% (3 of 6, PTLD complete remission) |
| [62] |
N = 114, 8.4 (0.5–38) years | EBV | 0.6–4 × 106 cell dose/kg | Prophylactic infusion (N = 101)/Therapeutic infusion (positive PTLD, N = 13): days not defined | Not defined |
| [63] |
N = 10, 15 (8.3–23.5) years | EBV | 2.5–5 × 104 cell dose/kg | Therapeutic infusion: 131 (97–188) days | R: 70% (7 of 10) |
| [48] |
N = 16, Mean (SD): 35.6 (21.6) years | BKV | 6 × 105 cell dose/kg | Therapeutic infusion: days not defined | R: 100% (16 of 16) |
| [54] |
N = 6, 15 (9.8–18.8) years | BKV | 1.6–6 × 105 cell dose/kg | Therapeutic infusion: 75 (60.3–101.8) days | R: 100% (6 of 6) |
| [64] |
N = 59, 47 (16–69) years | BKV | 2 × 105 cell dose/kg | Therapeutic infusion: 60 (60.3–101.8) days | R: 69.4% (34 of 49) PR: 12.2% (6 of 49) |
| [65] |
4. Adoptive Infusion of Treg Lymphocytes in the Promotion of Immune Tolerance
Patients Median (Range), Year | T Reg Manufacturing | Treg Cell Dose Median (Range) | Treg Clinical Indications | Timing of Infusion after HSCT | Clinical Outcome and Side Effects after Treg Infusion | Reference |
---|---|---|---|---|---|---|
N = 19, 39 (20–64) years | Expanded | 1–3 × 105 cell dose/kg | aGVHD prophylaxis/ immunological reconstitution | 1 infusion at day 0 |
| [87] |
N = 5, 49 (41–54) years | Expanded | 0.5–4.5 × 106 cell dose/kg | Refractory cGVHD/relapse prevention | 1 infusion after 35 (35–40) months post-HSCT; double infusion in N = 1 patients. |
| [86] |
N = 24, 45 (27–61) years | Expanded | 2.6 × 106 cell dose/kg | aGVHD prophylaxis/immunological reconstitution | 1 infusion at day 0 |
| [88] |
N = 28, 41 (21–60) years | Freshly isolated | 2–4 × 106 cell dose/kg | aGVHD prophylaxis/immunological reconstitution | 1 infusion at day −4 |
| [89] |
N = 24, 53 (43–56) years | Freshly isolated | 1–3 × 106 cell dose/kg | aGVHD prophylaxis/immunological reconstitution | 1 infusion at day 0 |
| [90] |
N = 41, 40 (18–65) years | Freshly isolated | 2.5 × 106 cell dose/kg | Relapse prevention | 1 infusion at day 0 |
| [91] |
5. Role of T Lymphocytes in Graft-Versus-Leukemia and Relapse
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Braidotti, S.; Granzotto, M.; Curci, D.; Faganel Kotnik, B.; Maximova, N. Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies. Biomedicines 2024, 12, 1853. https://doi.org/10.3390/biomedicines12081853
Braidotti S, Granzotto M, Curci D, Faganel Kotnik B, Maximova N. Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies. Biomedicines. 2024; 12(8):1853. https://doi.org/10.3390/biomedicines12081853
Chicago/Turabian StyleBraidotti, Stefania, Marilena Granzotto, Debora Curci, Barbara Faganel Kotnik, and Natalia Maximova. 2024. "Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies" Biomedicines 12, no. 8: 1853. https://doi.org/10.3390/biomedicines12081853
APA StyleBraidotti, S., Granzotto, M., Curci, D., Faganel Kotnik, B., & Maximova, N. (2024). Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies. Biomedicines, 12(8), 1853. https://doi.org/10.3390/biomedicines12081853