Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Different Non-T-Cell Depletion Protocols

Xiao-Di Ma , Zheng-Li Xu , Xiao-Jun Huang

MedComm ›› 2025, Vol. 6 ›› Issue (6) : e70206

PDF
MedComm ›› 2025, Vol. 6 ›› Issue (6) :e70206 DOI: 10.1002/mco2.70206
REVIEW

Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Different Non-T-Cell Depletion Protocols

Author information +
History +
PDF

Abstract

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as a critical treatment for hematological diseases. However, challenges, such as graft rejection and graft-versus-host disease (GVHD), have historically been faced with this procedure. Immune reconstitution (IR) has been shown to have profound effects on posttransplantation complications, such as relapse, infections, and GVHD. Recent advances in non-T-cell depletion protocols including the Beijing protocol and Baltimore protocol have significantly influenced the outcomes of haplo-HSCT by improving IR. Clinical studies and multiomic analyses have revealed that different protocols offer distinct mechanisms for IR patterns and further influence clinical outcomes. However, there is a lack of comprehensive reviews that systematically link the differences in IR between two protocols to their clinical outcomes, which leaves a critical gap in understanding the optimal strategies for IR in haplo-HSCT. This review provides an analysis of IR following haplo-HSCT with different protocols; it compares the clinical outcomes of various protocols, addresses the role of each immune cell subset in influencing outcomes and discusses emerging strategies aimed at improving IR. This review highlights the importance of ongoing research for improving immune reconstitution strategies, ultimately reducing posttransplant complications and offering targeted treatments to improve patient outcomes.

Keywords

immune reconstitution / haploidentical hematopoietic stem cell transplantation / conditioning regimen / posttransplant cyclophosphamide

Cite this article

Download citation ▾
Xiao-Di Ma, Zheng-Li Xu, Xiao-Jun Huang. Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Different Non-T-Cell Depletion Protocols. MedComm, 2025, 6(6): e70206 DOI:10.1002/mco2.70206

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

J. R. Passweg, H. Baldomero, P. Bader, et al., “Use of Haploidentical Stem Cell Transplantation Continues to Increase: The 2015 European Society for Blood and Marrow Transplant Activity Survey Report,” Bone Marrow Transplantation 52, no. 6 (2017): 811-817.

[2]

L.-P. Xu, P.-H. Lu, D.-P. Wu, et al., “Hematopoietic Stem Cell Transplantation Activity in China 2022-2023. The Proportions of Peripheral Blood for Stem Cell Source Continue to Grow: A Report From the Chinese Blood and Marrow Transplantation Registry Group,” Bone Marrow Transplantation (2024), https://doi.org/10.1038/s41409-024-02419-8.

[3]

J. R. Passweg, H. Baldomero, C. Chabannon, et al., “Hematopoietic Cell Transplantation and Cellular Therapy Survey of the EBMT: Monitoring of Activities and Trends Over 30 Years,” Bone Marrow Transplantation 56, no. 7 (2021): 1651-1664.

[4]

J. Apperley, D. Niederwieser, X.-J. Huang, et al., “Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States,” Biology of Blood and Marrow Transplantation 22, no. 1 (2016): 23-26.

[5]

J. Ogonek, M. Kralj Juric, S. Ghimire, et al., “Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation,” Frontiers in Immunology 7 (2016): 507.

[6]

K. Kurata, K. Yakushijin, I. Mizuno, et al., “Early Lymphocyte Recovery Predicts Clinical Outcome After HSCT With Mycophenolate Mofetil Prophylaxis in the Japanese Population,” International Journal of Hematology 108, no. 1 (2018): 58-65.

[7]

R. Fedele, M. Martino, C. Garreffa, et al., “The Impact of Early CD4+ Lymphocyte Recovery on the Outcome of Patients Who Undergo Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplantation,” Blood Transfus 10, no. 2 (2012): 174-180.

[8]

I. H. Bartelink, S. V. Belitser, C. A. J. Knibbe, et al., “Immune Reconstitution Kinetics as an Early Predictor for Mortality Using Various Hematopoietic Stem Cell Sources in Children,” Biology of Blood and Marrow Transplantation 19, no. 2 (2013): 305-313.

[9]

J. Storek, M. A. Dawson, B. Storer, et al., “Immune Reconstitution After Allogeneic Marrow Transplantation Compared With Blood Stem Cell Transplantation,” Blood 97, no. 11 (2001): 3380-3389.

[10]

P. J. Podgorny, Y. Liu, P. Dharmani-Khan, et al., “Immune Cell Subset Counts Associated With Graft-versus-host Disease,” Biology of Blood and Marrow Transplantation 20, no. 4 (2014): 450-462.

[11]

U. Koehl, K. Bochennek, S. Y. Zimmermann, et al., “Immune Recovery in Children Undergoing Allogeneic Stem Cell Transplantation: Absolute CD8+ CD3+ Count Reconstitution Is Associated With Survival,” Bone Marrow Transplantation 39, no. 5 (2007): 269-278.

[12]

L. E. Duinhouwer, N. Beije, B. van der Holt, et al., “Impaired Thymopoiesis Predicts for a High Risk of Severe Infections After Reduced Intensity Conditioning Without Anti-thymocyte Globulin in Double Umbilical Cord Blood Transplantation,” Bone Marrow Transplantation 53, no. 6 (2018): 673-682.

[13]

J. A. Brown, K. Stevenson, H. T. Kim, et al., “Clearance of CMV Viremia and Survival After Double Umbilical Cord Blood Transplantation in Adults Depends on Reconstitution of Thymopoiesis,” Blood 115, no. 20 (2010): 4111-4119.

[14]

K. Weinberg, B. R. Blazar, J. E. Wagner, et al., “Factors Affecting Thymic Function After Allogeneic Hematopoietic Stem Cell Transplantation,” Blood 97, no. 5 (2001): 1458-1466.

[15]

M. Bosch, M. Dhadda, M. Hoegh-Petersen, et al., “Immune Reconstitution After Anti-thymocyte Globulin-conditioned Hematopoietic Cell Transplantation,” Cytotherapy 14, no. 10 (2012): 1258-1275.

[16]

F. Aversa, A. Tabilio, A. Terenzi, et al., “Successful Engraftment of T-cell-depleted Haploidentical “Three-loci” Incompatible Transplants in Leukemia Patients by Addition of Recombinant human Granulocyte Colony-stimulating Factor-mobilized Peripheral Blood Progenitor Cells to Bone Marrow Inoculum,” Blood 84, no. 11 (1994): 3948-3955.

[17]

F. Aversa, A. Tabilio, A. Velardi, et al., “Treatment of High-risk Acute Leukemia With T-cell-depleted Stem Cells From Related Donors With One Fully Mismatched HLA Haplotype,” New England Journal of Medicine 339, no. 17 (1998): 1186-1193.

[18]

F. Aversa, “Setting the Standard in T-cell-depleted Haploidentical Transplantation and Beyond,” Best Practice & Research, Clinical Haematology 24, no. 3 (2011): 325-329.

[19]

F. Aversa, A. Terenzi, A. Tabilio, et al., “Full Haplotype-mismatched Hematopoietic Stem-cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse,” Journal of Clinical Oncology 23, no. 15 (2005): 3447-3454.

[20]

D.-P. Lu, L. Dong, T. Wu, et al., “Conditioning Including Antithymocyte Globulin Followed by Unmanipulated HLA-mismatched/Haploidentical Blood and Marrow Transplantation Can Achieve Comparable Outcomes With HLA-identical Sibling Transplantation,” Blood 107, no. 8 (2006): 3065-3073.

[21]

Y. J. Chang and X. J. Huang, “Haploidentical Hematopoietic Stem Cell Transplantation With Unmanipulated Granulocyte Colony Stimulating Factor Mobilized Marrow and Blood Grafts,” Current Opinion in Hematology 19, no. 6 (2012): 454-461.

[22]

X. J. Huang, D. H. Liu, K. Y. Liu, et al., “Haploidentical Hematopoietic Stem Cell Transplantation Without in Vitro T-cell Depletion for the Treatment of Hematological Malignancies,” Bone Marrow Transplantation 38, no. 4 (2006): 291-297.

[23]

L. Luznik, P. V. O'Donnell, H. J. Symons, et al., “HLA-haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-dose, Posttransplantation Cyclophosphamide,” Biology of Blood and Marrow Transplantation 14, no. 6 (2008): 641-650.

[24]

Y.-J. Chang, X.-Y. Zhao, M.-R. Huo, et al., “Immune Reconstitution Following Unmanipulated HLA-mismatched/Haploidentical Transplantation Compared With HLA-identical Sibling Transplantation,” Journal of Clinical Immunology 32, no. 2 (2012): 268-280.

[25]

X. Pei, X. Zhao, Y. Wang, et al., “Comparison of Reference Values for Immune Recovery Between Event-free Patients Receiving Haploidentical Allografts and Those Receiving human Leukocyte Antigen-matched Sibling Donor Allografts,” Frontiers of Medicine 12, no. 2 (2018): 153-163.

[26]

X. C.-H. Tsai, T.-T. Chen, J.-P. Gau, et al., “Outcomes of Different Haploidentical Transplantation Strategies From the Taiwan Blood and Marrow Transplantation Registry,” Cancers (Basel) 14, no. 4 (2022), https://doi.org/10.3390/cancers14041097.

[27]

X. Y. Pei, X. Y. Zhao, L. P. Xu, et al., “Immune Reconstitution in Patients With Acquired Severe Aplastic Anemia After Haploidentical Stem Cell Transplantation,” Bone Marrow Transplantation 52, no. 11 (2017): 1556-1562.

[28]

D.-M. Tian, Y. Wang, X.-H. Zhang, K.-Y. Liu, X.-J. Huang, and Y.-J. Chang, “Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival After Unmanipulated Haploidentical Blood and Marrow Transplantation,” PLoS ONE 11, no. 6 (2016): e0156777.

[29]

H. Guo, L. Guo, B. Wang, et al., “Distinct Immune Homeostasis Remodeling Patterns After HLA-Matched and Haploidentical Transplantation,” Adv Sci (Weinh) (2024): e2400544, https://doi.org/10.1002/advs.202400544.

[30]

R. V. Pandey, J. Strobl, A. Redl, et al., “Epigenetic Regulation of T Cell Lineages in Skin and Blood Following Hematopoietic Stem Cell Transplantation,” Clinical Immunology 248 (2023): 109245.

[31]

R. Massoud, N. Gagelmann, U. Fritzsche-Friedland, et al., “Comparison of Immune Reconstitution Between Anti-T-lymphocyte Globulin and Posttransplant Cyclophosphamide as Acute Graft-versus-host Disease Prophylaxis in Allogeneic Myeloablative Peripheral Blood Stem Cell Transplantation,” Haematologica 107, no. 4 (2022): 857-867.

[32]

A. Toubert, S. Glauzy, C. Douay, and E. Clave, “Thymus and Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation in Humans: Never Say Never Again,” Tissue Antigens 79, no. 2 (2012): 83-89.

[33]

N. G. van der Maas, D. Berghuis, M. van der Burg, and A. C. Lankester, “B Cell Reconstitution and Influencing Factors after Hematopoietic Stem Cell Transplantation in Children,” Frontiers in immunology 10 (2019): 782.

[34]

E. Velardi and J. J. Tsai, “van den Brink MRM. T Cell Regeneration After Immunological Injury,” Nature Reviews Immunology 21, no. 5 (2021): 277-291.

[35]

K. M. Williams, F. T. Hakim, and R. E. Gress, “T Cell Immune Reconstitution Following Lymphodepletion,” Seminars In Immunology 19, no. 5 (2007): 318-330.

[36]

B. J. Lee, P. Vittayawacharin, S. P. Griffin, et al., “Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients With Early Coronavirus Disease 2019 Infection,” Transplant Cell Ther 30, no. 8 (2024), https://doi.org/10.1016/j.jtct.2024.04.021.

[37]

N. Merindol, M. A. Champagne, M. Duval, and H. Soudeyns, “CD8(+) T-cell Reconstitution in Recipients of Umbilical Cord Blood Transplantation and Characteristics Associated With Leukemic Relapse,” Blood 118, no. 16 (2011): 4480-4488.

[38]

M. Di Ianni, F. Falzetti, A. Carotti, et al., “Tregs Prevent GVHD and Promote Immune Reconstitution in HLA-haploidentical Transplantation,” Blood 117, no. 14 (2011): 3921-3928.

[39]

R. C. Ash, M. M. Horowitz, R. P. Gale, et al., “Bone Marrow Transplantation From Related Donors Other Than HLA-identical Siblings: Effect of T Cell Depletion,” Bone Marrow Transplantation 7, no. 6 (1991): 443-452.

[40]

F. Ciceri, M. Labopin, F. Aversa, et al., “A Survey of Fully Haploidentical Hematopoietic Stem Cell Transplantation in Adults With High-risk Acute Leukemia: A Risk Factor Analysis of Outcomes for Patients in Remission at Transplantation,” Blood 112, no. 9 (2008): 3574-3581.

[41]

W. A. Bethge, M. Eyrich, S. Mielke, et al., “Results of a Multicenter Phase I/II Trial of TCRαβ and CD19-depleted Haploidentical Hematopoietic Stem Cell Transplantation for Adult and Pediatric Patients,” Bone Marrow Transplantation 57, no. 3 (2022): 423-430.

[42]

E. Salzmann-Manrique, M. Bremm, S. Huenecke, et al., “Joint Modeling of Immune Reconstitution Post Haploidentical Stem Cell Transplantation in Pediatric Patients with Acute Leukemia Comparing CD34(+)-Selected to CD3/CD19-Depleted Grafts in a Retrospective Multicenter Study,” Frontiers in immunology 9 (2018): 1841.

[43]

G. Li Pira, D. Malaspina, E. Girolami, et al., “Selective Depletion of Αβ T Cells and B Cells for Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency,” Biology of Blood and Marrow Transplantation 22, no. 11 (2016): 2056-2064.

[44]

P. Merli, D. Pagliara, F. Galaverna, et al., “TCRαβ/CD19 Depleted HSCT From an HLA-haploidentical Relative to Treat Children With Different Nonmalignant Disorders,” Blood Adv 6, no. 1 (2022): 281-292.

[45]

C. Tsilifis, S. H. Lum, Z. Nademi, et al., “TCRαβ-Depleted Haploidentical Grafts Are a Safe Alternative to HLA-Matched Unrelated Donor Stem Cell Transplants for Infants With Severe Combined Immunodeficiency,” Journal of Clinical Immunology 42, no. 4 (2022): 851-858.

[46]

N. Or-Geva and Y. Reisner, “The Evolution of T-cell Depletion in Haploidentical Stem-cell Transplantation,” British Journal of Haematology 172, no. 5 (2016): 667-684.

[47]

I. Airoldi, A. Bertaina, I. Prigione, et al., “γδ T-cell Reconstitution After HLA-haploidentical Hematopoietic Transplantation Depleted of TCR-αβ+/CD19+ Lymphocytes,” Blood 125, no. 15 (2015): 2349-2358.

[48]

A. Bacigalupo, A. Lankester, F. Ciceri, A. Bertaina., and H. C. T Haploidentical. In: Sureda A, Corbacioglu S, Greco R, Kröger N, Carreras E. (Springer, 2024): 577-585. Copyright 2024, The Author(s).

[49]

Y. Wang, Q.-F. Liu, L.-P. Xu, et al., “Haploidentical vs Identical-sibling Transplant for AML in Remission: A Multicenter, Prospective Study,” Blood 125, no. 25 (2015): 3956-3962.

[50]

N. Ghosh, R. Karmali, V. Rocha, et al., “Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis,” Journal of Clinical Oncology 34, no. 26 (2016): 3141-3149.

[51]

A. Di Stasi, D. R. Milton, L. M. Poon, et al., “Similar Transplantation Outcomes for Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients With Haploidentical versus 10/10 human Leukocyte Antigen-matched Unrelated and Related Donors,” Biology of Blood and Marrow Transplantation 20, no. 12 (2014): 1975-1981.

[52]

Y. Wang, D. P. Wu, Q. F. Liu, et al., “Low-dose Post-transplant Cyclophosphamide and Anti-thymocyte Globulin as an Effective Strategy for GVHD Prevention in Haploidentical Patients,” Journal of Hematology & Oncology 12, no. 1 (2019): 88.

[53]

F. Tang, Y. Xu, H. Chen, et al., “Comparison of the Clinical Outcomes of Hematologic Malignancies After Myeloablative Haploidentical Transplantation With G-CSF/ATG and Posttransplant Cyclophosphamide: Results From the Chinese Bone Marrow Transplantation Registry Group (CBMTRG),” Sci China Life Sci 63, no. 4 (2020): 571-581.

[54]

Y. Lu, Y. L. Zhao, J. P. Zhang, et al., “Comparable Outcomes Among Unmanipulated Haploidentical, Matched Unrelated, and Matched Sibling Donors in BU-based Myeloablative Hematopoietic Stem Cell Transplantation for Intermediate and Adverse Risk Acute Myeloid Leukemia in Complete Remission: A Single-center Study,” Annal of Hematology 100, no. 6 (2021): 1579-1591.

[55]

Z. L. Xu, L. P. Xu, D. P. Wu, et al., “Comparable Long-term Outcomes Between Upfront Haploidentical and Identical Sibling Donor Transplant in Aplastic Anemia: A National Registry-based Study,” Haematologica 107, no. 12 (2022): 2918-2927.

[56]

M. Barkhordar, A. Kasaeian, G. Janbabai, et al., “Modified Combination of Anti-thymocyte Globulin (ATG) and Post-transplant Cyclophosphamide (PTCy) as Compared With Standard ATG Protocol in Haploidentical Peripheral Blood Stem Cell Transplantation for Acute Leukemia,” Frontiers in Immunology 13 (2022): 921293.

[57]

D. Yao, Y. Tian, J. Li, et al., “Association Between Haploidentical Hematopoietic Stem Cell Transplantation Combined With an Umbilical Cord Blood Unit and Graft-versus-host Disease in Pediatric Patients With Acquired Severe Aplastic Anemia,” Ther Adv Hematol 13 (2022): 20406207221134409.

[58]

W. Zhang, R. Gui, Y. Zu, et al., “Reduced-dose Post-transplant Cyclophosphamide plus Low-dose Post-transplant Anti-thymocyte Globulin as Graft-versus-host Disease Prophylaxis With Fludarabine-busulfan-cytarabine Conditioning in Haploidentical Peripheral Blood Stem Cell Transplantation: A Multicentre, Randomized Controlled Clinical Trial,” British Journal of Haematology 200, no. 2 (2023): 210-221.

[59]

J. Cao, R. Pei, Y. Lu, et al., “Fludarabine and Antithymocyte Globulin-based Conditioning Regimen Combined With Post-transplantation Cyclophosphamide for Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in Patients With High-risk Acute Myeloid Leukemia and Myelodysplastic Syndrome,” Curr Res Transl Med 71, no. 1 (2023): 103360.

[60]

Z.-L. Xu, J. Ji, S.-B. Wang, et al., “Clinical Outcomes of Three Haploidentical Transplantation Protocols for Hematologic Malignancies Based on Data From the Chinese Bone Marrow Transplantation Registry Group,” Haematologica (2024), https://doi.org/10.3324/haematol.2024.286040.

[61]

J. Xiao, X. Yang, N. Wu, et al., “Modified G-CSF/ATG-Based Haploidentical Transplantation Protocol in Pediatric Primary Hemophagocytic Lymphohistiocytosis: A Long-Term Follow-Up Single-Center Experience,” Pediatric blood & cancer 72, no. 3 (2025): e31495.

[62]

D. R. Makanga, T. Guillaume, C. Willem, et al., “Posttransplant Cyclophosphamide and Antithymocyte Globulin versus Posttransplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis for Peripheral Blood Stem Cell Haploidentical Transplants: Comparison of T Cell and NK Effector Reconstitution,” Journal of Immunology 205, no. 5 (2020): 1441-1448.

[63]

J. Sugita, T. Kamimura, T. Ishikawa, et al., “Reduced Dose of Posttransplant Cyclophosphamide in HLA-haploidentical Peripheral Blood Stem Cell Transplantation,” Bone Marrow Transplantation 56, no. 3 (2021): 596-604.

[64]

F. Saglio, M. Berger, M. Spadea, et al., “Haploidentical HSCT With Post Transplantation Cyclophosphamide versus Unrelated Donor HSCT in Pediatric Patients Affected by Acute Leukemia,” Bone Marrow Transplantation 56, no. 3 (2021): 586-595.

[65]

G. Battipaglia, M. Labopin, D. Blaise, et al., “Impact of the Addition of Antithymocyte Globulin to Post-Transplantation Cyclophosphamide in Haploidentical Transplantation With Peripheral Blood Compared to Post-Transplantation Cyclophosphamide Alone in Acute Myelogenous Leukemia: A Retrospective Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation,” Transplant Cell Ther 28, no. 9 (2022): 587.e1-587.e7.

[66]

F. Baron, M. Labopin, J. Tischer, et al., “Comparison of HLA-mismatched Unrelated Donor Transplantation With Post-transplant Cyclophosphamide versus HLA-haploidentical Transplantation in Patients With Active Acute Myeloid Leukemia,” Bone Marrow Transplantation 57, no. 11 (2022): 1657-1663.

[67]

A. E. DeZern, M. Zahurak, H. J. Symons, et al., “Alternative Donor BMT With Posttransplant Cyclophosphamide as Initial Therapy for Acquired Severe Aplastic Anemia,” Blood 141, no. 25 (2023): 3031-3038.

[68]

R. Duléry, C. Goudet, D. Mannina, et al., “Reduced Post-transplant Cyclophosphamide Doses in Haploidentical Hematopoietic Cell Transplantation for Elderly Patients With Hematological Malignancies,” Bone Marrow Transplantation 58, no. 4 (2023): 386-392.

[69]

S. Arslan, A. Desai, D. Yang, et al., “Total Body Irradiation and Fludarabine With Post-Transplantation Cyclophosphamide for Mismatched Related or Unrelated Donor Hematopoietic Cell Transplantation,” Transplant Cell Ther 30, no. 10 (2024): 1013.e1-1013.e12.

[70]

A. Ruggeri, N. Santoro, J. E. Galimard, et al., “Matched Unrelated Donor Transplantation versus Haploidentical Transplantation With Post-transplant Cyclophosphamide in Children With Acute Myeloid Leukemia: A PDWP-EBMT Study,” Haematologica 109, no. 7 (2024): 2122-2130.

[71]

K. Harada, J. Kanda, M. Hirayama, et al., “Comparison of Nonrelapse Mortality after Haploidentical Hematopoietic Stem Cell Transplantation with Post-transplant Cyclophosphamide versus Single Umbilical Cord Blood Transplantation in Hematologic Disease,” Transplant Cell Ther 31, no. 2 (2025): 103.e1-103.e13.

[72]

X.-J. Huang, W. Han, L.-P. Xu, et al., “A Novel Approach to HLA-mismatched Transplantation,” Beijing Da Xue Bao Yi Xue Ban 36, no. 3 (2004): 229-233.

[73]

X. J. Huang, “Haploidentical Hematopoietic Stem Cell Transplantation Without in Vitro T-cell-depletion for the Treatment of Hematologic Diseases,” Chimerism 4, no. 1 (2013): 26-28.

[74]

C.-H. Yan, Y. Wang, J.-Z. Wang, et al., “Minimal Residual Disease- and Graft-vs.-host Disease-guided Multiple Consolidation Chemotherapy and Donor Lymphocyte Infusion Prevent Second Acute Leukemia Relapse After Allotransplant,” Journal of hematology & oncology 9, no. 1 (2016): 87.

[75]

Y.-J. Chang, L.-P. Xu, Y. Wang, et al., “Controlled, Randomized, Open-Label Trial of Risk-Stratified Corticosteroid Prevention of Acute Graft-Versus-Host Disease after Haploidentical Transplantation,” Journal of Clinical Oncology 34, no. 16 (2016): 1855-1863.

[76]

Y. Wang, Y.-J. Chang, L.-P. Xu, et al., “Who Is the Best Donor for a Related HLA Haplotype-mismatched Transplant?,” Blood 124, no. 6 (2014): 843-850.

[77]

Y. Q. Sun, L. P. Xu, X. H. Zhang, et al., “A Retrospective Comparison of BU-fludarabine and BU-CY Regimens in Elderly Patients or in Patients With Comorbidities Who Received Unmanipulated Haploidentical Hematopoietic SCT,” Bone Marrow Transplantation 50, no. 4 (2015): 601-603.

[78]

Y. Wang, D.-H. Liu, K.-Y. Liu, et al., “Long-term Follow-up of Haploidentical Hematopoietic Stem Cell Transplantation Without in Vitro T Cell Depletion for the Treatment of Leukemia: Nine Years of Experience at a Single Center,” Cancer 119, no. 5 (2013): 978-985.

[79]

L.-P. Xu, Z.-L. Xu, S.-Q. Wang, et al., “Long-term Follow-up of Haploidentical Transplantation in Relapsed/Refractory Severe Aplastic Anemia: A Multicenter Prospective Study,” Sci Bull (Beijing) 67, no. 9 (2022): 963-970.

[80]

L. Q. Cao, W. X. Huo, X. H. Zhang, et al., “Peripheral Blood Stem Cell Transplantation From Haploidentical Related Donor Could Achieve Satisfactory Clinical Outcomes for Intermediate- or High-risk Adult Acute Myeloid Leukemia Patients,” Bone Marrow Transplantation 59, no. 2 (2024): 203-210.

[81]

R. Duléry, R. Mohty, M. Labopin, et al., “Early Cardiac Toxicity Associated with Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation,” JACC CardioOncol 3, no. 2 (2021): 250-259.

[82]

M. J. McAdams, M. Hyder, D. Dimitrova, et al., “Phase I/II Study of Reduced Dosing of Post-Transplantation Cyclophosphamide (PTCy) After HLA-Haploidentical Bone Marrow Transplantation,” Blood 138, Supplement no. 1 (2021): 101-101.

[83]

M. A. Hyder, D. Dimitrova, R. Sabina, et al., “Intermediate-Dose Post-Transplantation Cyclophosphamide for Myeloablative HLA-Haploidentical Bone Marrow Transplantation,” Blood Adv (2025), https://doi.org/10.1182/bloodadvances.2024014879.

[84]

S. Fuji, H. Nakamae, J. Sugita, et al., “Lower-dose Post-transplant Cyclophosphamide in Haploidentical Hematopoietic Cell Transplantation,” Bone Marrow Transplantation 59, no. 11 (2024): 1628-1630.

[85]

A. Ruggeri, M. Labopin, E. Angelucci, et al., “Prognostic Factors for Neutrophil Engraftment After Haploidentical Cell Transplantation With PT-Cy in Patients With Acute Myeloid Leukemia in Complete Remission, on Behalf of the ALWP-EBMT,” Bone Marrow Transplantation 56, no. 8 (2021): 1842-1849.

[86]

K. Raj, A. Pagliuca, K. Bradstock, et al., “Peripheral Blood Hematopoietic Stem Cells for Transplantation of Hematological Diseases From Related, Haploidentical Donors After Reduced-intensity Conditioning,” Biology of Blood and Marrow Transplantation 20, no. 6 (2014): 890-895.

[87]

C. Marcoux, D. Marin, J. Ramdial, et al., “Younger Haploidentical Donor versus Older Matched Unrelated Donor for Patients With AML/MDS,” American Journal of Hematology 98, no. 5 (2023): 712-719.

[88]

R. S. Mehta, D. Marin, A. Alousi, et al., “Haploidentical vs Matched Unrelated Donors for Patients With ALL: Donor Age Matters More Than Donor Type,” Blood Adv 7, no. 8 (2023): 1594-1603.

[89]

M. Leick, R. M. Gittelman, E. Yusko, et al., “T Cell Clonal Dynamics Determined by High-Resolution TCR-β Sequencing in Recipients After Allogeneic Hematopoietic Cell Transplantation,” Biology of Blood and Marrow Transplantation 26, no. 9 (2020): 1567-1574.

[90]

A. Schäfer, Z. Calderin Sollet, M. P. Hervé, et al., “NK- and T-cell Repertoire Is Established Early After Allogeneic HSCT and Is Imprinted by CMV Reactivation,” Blood Adv 8, no. 21 (2024): 5612-5624.

[91]

H. X. Jun, C. Y. Jun, and Z. X. Yu, “In Vivo Induction of T-cell Hyporesponsiveness and Alteration of Immunological Cells of Bone Marrow Grafts Using Granulocyte Colony-stimulating Factor,” Haematologica 89, no. 12 (2004): 1517-1524.

[92]

M. Gooptu, H. T. Kim, Y.-B. Chen, et al., “Effect of Antihuman T Lymphocyte Globulin on Immune Recovery After Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial,” Biology of Blood and Marrow Transplantation 24, no. 11 (2018): 2216-2223.

[93]

A. T. Turki, V. Klisanin, E. Bayraktar, et al., “Optimizing Anti-T-lymphocyte Globulin Dosing to Improve Long-term Outcome After Unrelated Hematopoietic Cell Transplantation for Hematologic Malignancies,” American Journal of Transplantation 20, no. 3 (2020): 677-688.

[94]

C. G. Kanakry, S. Ganguly, M. Zahurak, et al., “Aldehyde Dehydrogenase Expression Drives human Regulatory T Cell Resistance to Posttransplantation Cyclophosphamide,” Science Translational Medicine 5, no. 211 (2013): 211ra157.

[95]

M. Eto, H. Mayumi, Y. Tomita, et al., “Specific Destruction of Host-reactive Mature T Cells of Donor Origin Prevents Graft-versus-host Disease in Cyclophosphamide-induced Tolerant Mice,” Journal of Immunology 146, no. 5 (1991): 1402-1409.

[96]

X. Pei, X. Zhao, Y. Wang, et al., “Comparison of Reference Values for Immune Recovery Between Event-free Patients Receiving Haploidentical Allografts and Those Receiving human Leukocyte Antigen-matched Sibling Donor Allografts,” Front Med 12, no. 2 (2018): 153-163.

[97]

C. Retière, C. Willem, T. Guillaume, et al., “Impact on Early Outcomes and Immune Reconstitution of High-dose Post-transplant Cyclophosphamide vs Anti-thymocyte Globulin After Reduced Intensity Conditioning Peripheral Blood Stem Cell Allogeneic Transplantation,” Oncotarget 9, no. 14 (2018): 11451-11464.

[98]

L. J. DeCook, M. Thoma, T. Huneke, et al., “Impact of Lymphocyte and Monocyte Recovery on the Outcomes of Allogeneic Hematopoietic SCT With Fludarabine and Melphalan Conditioning,” Bone Marrow Transplantation 48, no. 5 (2013): 708-714.

[99]

A. Bashey, M. J. Zhang, S. R. McCurdy, et al., “Mobilized Peripheral Blood Stem Cells versus Unstimulated Bone Marrow as a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide,” Journal of Clinical Oncology 35, no. 26 (2017): 3002-3009.

[100]

C. Hong, H. Lu, X. Huang, et al., “Neutrophils as Regulators of Macrophage-induced Inflammation in a Setting of Allogeneic Bone Marrow Transplantation,” Stem Cell Reports 17, no. 7 (2022): 1561-1575.

[101]

Y.-J. Chang, X.-Y. Zhao, and X.-J. Huang, “Effects of the NK Cell Recovery on Outcomes of Unmanipulated Haploidentical Blood and Marrow Transplantation for Patients With Hematologic Malignancies,” Biology of Blood and Marrow Transplantation: Journal of the American Society For Blood and Marrow Transplantation 14, no. 3 (2008): 323-334.

[102]

A. Raiola, A. Dominietto, R. Varaldo, et al., “Unmanipulated Haploidentical BMT Following Non-myeloablative Conditioning and Post-transplantation CY for Advanced Hodgkin's Lymphoma,” Bone Marrow Transplantation 49, no. 2 (2014): 190-194.

[103]

X. Y. Zhao, X. J. Huang, K. Y. Liu, L. P. Xu, and D. H. Liu, “Prognosis After Unmanipulated HLA-haploidentical Blood and Marrow Transplantation Is Correlated to the Numbers of KIR Ligands in Recipients,” European Journal of Haematology 78, no. 4 (2007): 338-346.

[104]

J. Liu, Z. Bian, X. Wang, et al., “Inverse Correlation of Vδ2+ T-cell Recovery With EBV Reactivation After Haematopoietic Stem Cell Transplantation,” British Journal of Haematology 180, no. 2 (2018): 276-285.

[105]

N. Stocker, B. Gaugler, M. Labopin, et al., “High-dose Post-transplant Cyclophosphamide Impairs Γδ T-cell Reconstitution After Haploidentical Haematopoietic Stem Cell Transplantation Using Low-dose Antithymocyte Globulin and Peripheral Blood Stem Cell Graft,” Clin Transl Immunology 9, no. 9 (2020): e1171.

[106]

L. C. M. Arruda, A. Gaballa, and M. Uhlin, “Impact of Γδ T Cells on Clinical Outcome of Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-analysis,” Blood Adv 3, no. 21 (2019): 3436-3448.

[107]

S. R. McCurdy, A. Vulic, H. J. Symons, et al., “Comparable and Robust Immune Reconstitution After HLA-Haploidentical or HLA-Matched Allogeneic Transplantation (BMT) Utilizing Posttransplantation Cyclophosphamide,” Biology of Blood and Marrow Transplantation 21, no. 2 (2015): S71.

[108]

M. Iwamoto, S. Ikegawa, T. Kondo, et al., “Post-transplantation Cyclophosphamide Restores Early B-cell Lymphogenesis That Suppresses Subsequent Chronic Graft-versus-host Disease,” Bone Marrow Transplantation 56, no. 4 (2021): 956-959.

[109]

A. Roberto, L. Castagna, S. Gandolfi, et al., “B-cell Reconstitution Recapitulates B-cell Lymphopoiesis Following Haploidentical BM Transplantation and Post-transplant CY,” Bone Marrow Transplantation 50, no. 2 (2015): 317-319.

[110]

M. Bosch, F. M. Khan, and J. Storek, “Immune Reconstitution After Hematopoietic Cell Transplantation,” Current Opinion in Hematology 19, no. 4 (2012): 324-335.

[111]

K. S. Peggs, “Reconstitution of Adaptive and Innate Immunity Following Allogeneic Hematopoietic Stem Cell Transplantation in Humans,” Cytotherapy 8, no. 5 (2006): 427-436.

[112]

K. Atkinson, J. C. Biggs, K. Downs, et al., “GM-CSF After Allogeneic Bone Marrow Transplantation: Accelerated Recovery of Neutrophils, Monocytes and Lymphocytes,” Australian and New Zealand Journal of Medicine 21, no. 5 (1991): 686-692.

[113]

M. D. Porta, G. M. Rigolin, E. P. Alessandrino, et al., “Dendritic Cell Recovery After Allogeneic Stem-cell Transplantation in Acute Leukemia: Correlations With Clinical and Transplant Characteristics,” European Journal of Haematology 72, no. 1 (2004): 18-25.

[114]

M. V. Gonçalves, M. Yamamoto, E. Y. S. Kimura, et al., “Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation,” Biology of Blood and Marrow Transplantation 21, no. 7 (2015): 1223-1229, https://doi.org/10.1016/j.bbmt.2015.03.010.

[115]

A. Roberto, C. Di Vito, E. Zaghi, et al., “The Early Expansion of Anergic NKG2Apos/CD56dim/CD16neg Natural Killer Represents a Therapeutic Target in Haploidentical Hematopoietic Stem Cell Transplantation,” Haematologica 103, no. 8 (2018): 1390-1402.

[116]

S. Cooley, P. Parham, and J. S. Miller, “Strategies to Activate NK Cells to Prevent Relapse and Induce Remission Following Hematopoietic Stem Cell Transplantation,” Blood 131, no. 10 (2018): 1053-1062.

[117]

H. G. Ljunggren and K. Kärre, “In Search of the ‘Missing Self’: MHC Molecules and NK Cell Recognition,” Immunology Today 11, no. 7 (1990): 237-244.

[118]

M. A. Cooper, T. A. Fehniger, and M. A. Caligiuri, “The Biology of human Natural Killer-cell Subsets,” Trends in Immunology 22, no. 11 (2001): 633-640.

[119]

L. Moretta, F. Locatelli, D. Pende, E. Marcenaro, M. C. Mingari, and A. Moretta, “Killer Ig-Like Receptor-mediated Control of Natural Killer Cell Alloreactivity in Haploidentical Hematopoietic Stem Cell Transplantation,” Blood 117, no. 3 (2011): 764-771.

[120]

A. Russo, G. Oliveira, S. Berglund, et al., “NK Cell Recovery After Haploidentical HSCT With Posttransplant Cyclophosphamide: Dynamics and Clinical Implications,” Blood 131, no. 2 (2018): 247-262.

[121]

Y. Hu, Q. Cui, C. Luo, Y. Luo, J. Shi, and H. Huang, “A Promising Sword of Tomorrow: Human Γδ T Cell Strategies Reconcile Allo-HSCT Complications,” Blood Reviews 30, no. 3 (2016): 179-188.

[122]

N. Xiong and D. H. Raulet, “Development and Selection of Gammadelta T Cells,” Immunological Reviews 215 (2007): 15-31.

[123]

Y. Hu, Q. Hu, Y. Li, et al., “γδ T Cells: Origin and Fate, Subsets, Diseases and Immunotherapy,” Signal Transduct Target Ther 8, no. 1 (2023): 434.

[124]

M. Hirokawa, T. Horiuchi, Y. Kawabata, A. Kitabayashi, and A. B. Miura, “Reconstitution of Gammadelta T Cell Repertoire Diversity After human Allogeneic Hematopoietic Cell Transplantation and the Role of Peripheral Expansion of Mature T Cell Population in the Graft,” Bone Marrow Transplantation 26, no. 2 (2000): 177-185.

[125]

S. Ravens, C. Schultze-Florey, S. Raha, et al., “Human Γδ T Cells Are Quickly Reconstituted After Stem-cell Transplantation and Show Adaptive Clonal Expansion in Response to Viral Infection,” Nature Immunology 18, no. 4 (2017): 393-401.

[126]

X. Wang, J. Liu, H. Gao, et al., “Dendritic Cells Are Critical for the Activation and Expansion of Vδ2+ T Cells after Allogeneic Hematopoietic Transplantation,” Frontiers in immunology 9 (2018): 2528.

[127]

R. Elfeky, A. Lazareva, W. Qasim, and P. Veys, “Immune Reconstitution Following Hematopoietic Stem Cell Transplantation Using Different Stem Cell Sources,” Expert Rev Clin Immunol 15, no. 7 (2019): 735-751.

[128]

M. S. Chaudhry, E. Velardi, F. Malard, and M. R. M. van den Brink, “Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation: Time To T up the Thymus,” Journal of Immunology 198, no. 1 (2017): 40-46.

[129]

S. Servais, C. Menten-Dedoyart, Y. Beguin, et al., “Impact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery After Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation,” PLoS ONE 10, no. 6 (2015): e0130026.

[130]

J. D. Fontenot and A. Y. Rudensky, “A Well Adapted Regulatory Contrivance: Regulatory T Cell Development and the Forkhead family Transcription Factor Foxp3,” Nature Immunology 6, no. 4 (2005): 331-337.

[131]

J. D. Fontenot, J. P. Rasmussen, L. M. Williams, J. L. Dooley, A. G. Farr, and A. Y. Rudensky, “Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor foxp3,” Immunity 22, no. 3 (2005): 329-341.

[132]

S. Sakaguchi, T. Yamaguchi, T. Nomura, and M. Ono, “Regulatory T Cells and Immune Tolerance,” Cell 133, no. 5 (2008): 775-787.

[133]

P. Hoffmann, J. Ermann, M. Edinger, C. G. Fathman, and S. Strober, “Donor-type CD4(+)CD25(+) Regulatory T Cells Suppress Lethal Acute Graft-versus-host Disease After Allogeneic Bone Marrow Transplantation,” Journal of Experimental Medicine 196, no. 3 (2002): 389-399.

[134]

J. M. Magenau, X. Qin, I. Tawara, et al., “Frequency of CD4(+)CD25(hi)FOXP3(+) Regulatory T Cells Has Diagnostic and Prognostic Value as a Biomarker for Acute Graft-versus-host-disease,” Biology of Blood and Marrow Transplantation 16, no. 7 (2010): 907-914.

[135]

A. Xhaard, H. Moins-Teisserenc, M. Busson, et al., “Reconstitution of Regulatory T-cell Subsets After Allogeneic Hematopoietic SCT,” Bone Marrow Transplantation 49, no. 8 (2014): 1089-1092.

[136]

Y. Wang, J. Liu, P. D. Burrows, and J.-Y. Wang, “B Cell Development and Maturation,” Advances in Experimental Medicine and Biology (2020): 1254, https://doi.org/10.1007/978-981-15-3532-1_1.

[137]

R. P. Witherspoon, R. Storb, H. D. Ochs, et al., “Recovery of Antibody Production in human Allogeneic Marrow Graft Recipients: Influence of Time Posttransplantation, the Presence or Absence of Chronic Graft-versus-host Disease, and Antithymocyte Globulin Treatment,” Blood 58, no. 2 (1981): 360-368.

[138]

M. Xie, H.-X. Fu, Y.-J. Chang, et al., “Characteristics and Influencing Factors of CD19+ B Cell Reconstitution in Patients Following Haploidentical/Mismatched Hematopoietic Stem Cell Transplantation,” International Journal of Hematology 96, no. 1 (2012): 109-121.

[139]

W. J. Kovacs, “To B or Not to B? Glucocorticoid Impact on B Lymphocyte Fate and Function,” Endocrinology 155, no. 2 (2014): 339-342.

[140]

L. A. Welniak, B. R. Blazar, and W. J. Murphy, “Immunobiology of Allogeneic Hematopoietic Stem Cell Transplantation,” Annual Review of Immunology 25 (2007): 139-170.

[141]

G. Zhou, Q. Zhan, L. Huang, et al., “The Dynamics of B-cell Reconstitution Post Allogeneic Hematopoietic Stem Cell Transplantation: A Real-world Study,” Journal of Internal Medicine 295, no. 5 (2024): 634-650.

[142]

K. H. Chu and B. L. Chiang, “A Novel Subset of Regulatory T Cells Induced by B Cells Alleviate the Severity of Immunological Diseases,” Clinical Reviews in Allergy & Immunology 67, no. 1-3 (2024): 73-82.

[143]

G. Raimondi, I. Zanoni, S. Citterio, P. Ricciardi-Castagnoli, and F. Granucci, “Induction of Peripheral T Cell Tolerance by Antigen-presenting B Cells. II. Chronic Antigen Presentation Overrules Antigen-presenting B Cell Activation,” Journal of Immunology 176, no. 7 (2006): 4021-4028.

[144]

L. Ruggeri, M. Capanni, M. Casucci, et al., “Role of Natural Killer Cell Alloreactivity in HLA-mismatched Hematopoietic Stem Cell Transplantation,” Blood 94, no. 1 (1999): 333-339.

[145]

Z. Zhou, X. Liu, X. Zhang, et al., “Impact of Early Natural Killer Cell Reconstitution on the Outcomes of T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation,” J Inflamm Res 16 (2023): 2993-3008.

[146]

L. M. Turcotte, Q. Cao, S. A. Cooley, et al., “Monocyte Subpopulation Recovery as Predictors of Hematopoietic Cell Transplantation Outcomes,” Biology of Blood and Marrow Transplantation 25, no. 5 (2019): 883-890.

[147]

Y.-J. Chang, X.-Y. Zhao, L.-P. Xu, et al., “Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome,” Leukemia & Lymphoma 54, no. 12 (2013): 2671-2677, https://doi.org/10.3109/10428194.2013.783912.

[148]

A. Perez-Corral, N. Dorado, V. Pradillo, et al., “Immune Reconstitution Impact on Overall Survival After Hematopoietic Haploidentical Stem Cell Transplantation,” Blood 128, no. 22 (2016): 5779.

[149]

Y. J. Chang, X. Y. Zhao, and X. J. Huang, “Effects of the NK Cell Recovery on Outcomes of Unmanipulated Haploidentical Blood and Marrow Transplantation for Patients With Hematologic Malignancies,” Biology of Blood and Marrow Transplantation 14, no. 3 (2008): 323-334.

[150]

L. Ruggeri, M. Capanni, E. Urbani, et al., “Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants,” Science 295, no. 5562 (2002): 2097-2100.

[151]

W. Leung, R. Iyengar, V. Turner, et al., “Determinants of Antileukemia Effects of Allogeneic NK Cells,” Journal of Immunology 172, no. 1 (2004): 644-650.

[152]

H. Olkinuora, K. Talvensaari, T. Kaartinen, et al., “T Cell Regeneration in Pediatric Allogeneic Stem Cell Transplantation,” Bone Marrow Transplantation 39, no. 3 (2007): 149-156.

[153]

R. Lin and Q. Liu, “Diagnosis and Treatment of Viral Diseases in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation,” Journal of hematology & oncology 6 (2013): 94.

[154]

J. Huang, Z. Pan, L. Wang, et al., “Early T-cell Reconstitution Predicts Risk of EBV Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation,” Clinical and Experimental Medicine 24, no. 1 (2024): 22.

[155]

Y. F. Huang, S. Y. Zhang, J. B. He, et al., “Early Cellular Immune Exhaustion in Patients With Epstein-Barr Virus Activation Following Haploidentical Hematopoietic Stem Cell Transplantation,” Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi 45, no. 11 (2024): 998-1004.

[156]

X.-Y. Pei, X.-Y. Zhao, X.-F. Liu, et al., “Adoptive Therapy With cytomegalovirus-specific T Cells for cytomegalovirus Infection After Haploidentical Stem Cell Transplantation and Factors Affecting Efficacy,” American Journal of Hematology 97, no. 6 (2022): 762-769.

[157]

E. Atilla, P. A. Atilla, S. C. Bozdağ, and T. Demirer, “A Review of Infectious Complications After Haploidentical Hematopoietic Stem Cell Transplantations,” Infection 45, no. 4 (2017): 403-411.

[158]

J. Storek, G. Espino, M. A. Dawson, B. Storer, M. E. Flowers, and D. G. Maloney, “Low B-cell and Monocyte Counts on Day 80 Are Associated With High Infection Rates Between Days 100 and 365 After Allogeneic Marrow Transplantation,” Blood 96, no. 9 (2000): 3290-3293.

[159]

E. Corre, M. Carmagnat, M. Busson, et al., “Long-term Immune Deficiency After Allogeneic Stem Cell Transplantation: B-cell Deficiency Is Associated With Late Infections,” Haematologica 95, no. 6 (2010): 1025-1029.

[160]

S. Maury, J.-Y. Mary, C. Rabian, et al., “Prolonged Immune Deficiency Following Allogeneic Stem Cell Transplantation: Risk Factors and Complications in Adult Patients,” British Journal of Haematology 115, no. 3 (2001): 630-641.

[161]

J. L. Ferrara, R. Levy, and N. J. Chao, “Pathophysiologic Mechanisms of Acute Graft-vs.-host Disease,” Biology of Blood and Marrow Transplantation 5, no. 6 (1999): 347-356.

[162]

W. Krenger, G. R. Hill, and J. L. M. Ferrara, “Cytokine Cascades in Acute Graft-versus-host disease1,” Transplantation 64, no. 4 (1997).

[163]

M. Edinger, P. Hoffmann, J. Ermann, et al., “CD4+CD25+ regulatory T Cells Preserve Graft-versus-tumor Activity While Inhibiting Graft-versus-host Disease After Bone Marrow Transplantation,” Nature Medicine 9, no. 9 (2003): 1144-1150.

[164]

K. Rezvani, S. Mielke, M. Ahmadzadeh, et al., “High Donor FOXP3-positive Regulatory T-cell (Treg) Content Is Associated With a Low Risk of GVHD Following HLA-matched Allogeneic SCT,” Blood 108, no. 4 (2006): 1291-1297.

[165]

M. Delia, D. Pastore, A. Mestice, et al., “Outcome of Allogeneic Peripheral Blood Stem Cell Transplantation by Donor Graft CD3+/Tregs Ratio: A Single-Center Experience,” Biology of Blood and Marrow Transplantation 19, no. 3 (2013): 495-499.

[166]

C. G. Brunstein, J. S. Miller, Q. Cao, et al., “Infusion of Ex Vivo Expanded T Regulatory Cells in Adults Transplanted With Umbilical Cord Blood: Safety Profile and Detection Kinetics,” Blood 117, no. 3 (2011): 1061-1070.

[167]

E. Zorn, H. T. Kim, S. J. Lee, et al., “Reduced Frequency of FOXP3+ CD4+CD25+ Regulatory T Cells in Patients With Chronic Graft-versus-host Disease,” Blood 106, no. 8 (2005): 2903-2911.

[168]

P. Trzonkowski, M. Bieniaszewska, J. Juścińska, et al., “First-in-man Clinical Results of the Treatment of Patients With Graft versus Host Disease With human Ex Vivo Expanded CD4+CD25+CD127- T Regulatory Cells,” Clinical Immunology 133, no. 1 (2009): 22-26.

[169]

M. S. Massei, I. Capolsini, E. Mastrodicasa, et al., “HLA-haploidentical Hematopoietic Stem Cells Transplantation With Regulatory and Conventional T-cell Adoptive Immunotherapy in Pediatric Patients With Very High-risk Acute Leukemia,” Bone Marrow Transplantation 58, no. 5 (2023): 526-533.

[170]

L. Gao, Y. Zhang, B. Hu, et al., “Phase II Multicenter, Randomized, Double-Blind Controlled Study of Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cells in the Prophylaxis of Chronic Graft-Versus-Host Disease after HLA-Haploidentical Stem-Cell Transplantation,” Journal of Clinical Oncology 34, no. 24 (2016): 2843-2850.

[171]

N. Pang, S. Tudahong, Y. Zhu, et al., “Galectin-9 Alleviates Acute Graft-versus-host Disease After Haplo-hematopoietic Stem Cell Transplantation by Regulating Regulatory T Cell/Effector T Cell Imbalance,” Immun Inflamm Dis 12, no. 2 (2024): e1177.

[172]

C. Cutler and J. H. Antin, “Sirolimus Immunosuppression for Graft-versus-host Disease Prophylaxis and Therapy: An Update,” Current Opinion in Hematology 17, no. 6 (2010): 500-504.

[173]

R. J. Soiffer, R. Gonin, C. Murray, et al., “Prediction of Graft-versus-host Disease by Phenotypic Analysis of Early Immune Reconstitution After CD6-depleted Allogeneic Bone Marrow Transplantation,” Blood 82, no. 7 (1993): 2216-2223.

[174]

R. Seggewiss and H. Einsele, “Immune Reconstitution After Allogeneic Transplantation and Expanding Options for Immunomodulation: An Update,” Blood 115, no. 19 (2010): 3861-3868.

[175]

A. Thiolat, C. Pilon, P. Caudana, et al., “Treg-targeted IL-2/Anti-IL-2 Complex Controls Graft-versus-host Disease and Supports Anti-tumor Effect in Allogeneic Hematopoietic Stem Cell Transplantation,” Haematologica 109, no. 1 (2024): 129-142.

[176]

O. Alpdogan, C. Schmaltz, S. J. Muriglan, et al., “Administration of Interleukin-7 After Allogeneic Bone Marrow Transplantation Improves Immune Reconstitution Without Aggravating Graft-versus-host Disease,” Blood 98, no. 7 (2001): 2256-2265.

[177]

G. Chen, D. Wu, Y. Wang, et al., “Expanded Donor Natural Killer Cell and IL-2, IL-15 Treatment Efficacy in Allogeneic Hematopoietic Stem Cell Transplantation,” European Journal of Haematology 81, no. 3 (2008): 226-235.

[178]

D. Min, P. A. Taylor, A. Panoskaltsis-Mortari, et al., “Protection From Thymic Epithelial Cell Injury by Keratinocyte Growth Factor: A New Approach to Improve Thymic and Peripheral T-cell Reconstitution After Bone Marrow Transplantation,” Blood 99, no. 12 (2002): 4592-4600.

[179]

R. Seggewiss, K. Loré, F. J. Guenaga, et al., “Keratinocyte Growth Factor Augments Immune Reconstitution After Autologous Hematopoietic Progenitor Cell Transplantation in rhesus Macaques,” Blood 110, no. 1 (2007): 441-449.

[180]

O. Alpdogan, S. J. Muriglan, B. J. Kappel, et al., “Insulin-Like Growth Factor-I Enhances Lymphoid and Myeloid Reconstitution After Allogeneic Bone Marrow Transplantation,” Transplantation 75, no. 12 (2003): 1977-1983.

[181]

A. Knyszynski, S. Adler-Kunin, and A. Globerson, “Effects of Growth Hormone on Thymocyte Development From Progenitor Cells in the Bone Marrow,” Brain, Behavior, and Immunity 6, no. 4 (1992): 327-340.

[182]

A. Lundqvist, J. P. McCoy, L. Samsel, and R. Childs, “Reduction of GVHD and Enhanced Antitumor Effects After Adoptive Infusion of Alloreactive Ly49-mismatched NK Cells From MHC-matched Donors,” Blood 109, no. 8 (2007): 3603-3606.

[183]

V. H. Nguyen, S. Shashidhar, D. S. Chang, et al., “The Impact of Regulatory T Cells on T-cell Immunity Following Hematopoietic Cell Transplantation,” Blood 111, no. 2 (2008): 945-953.

[184]

M. Sudres, F. Norol, A. Trenado, et al., “Bone Marrow Mesenchymal Stem Cells Suppress Lymphocyte Proliferation in Vitro but Fail to Prevent Graft-versus-Host Disease in Mice1,” The Journal of Immunology 176, no. 12 (2006): 7761-7767.

[185]

X. Y. Pei, X. F. Liu, X. Y. Zhao, et al., “Comparable Anti-CMV Responses of Transplant Donor and Third-party CMV-specific T Cells for Treatment of CMV Infection After Allogeneic Stem Cell Transplantation,” Cell Mol Immunol 19, no. 4 (2022): 482-491.

[186]

M. J. Reddehase, W. Mutter, K. Münch, H. J. Bühring, and U. H. Koszinowski, “CD8-positive T Lymphocytes Specific for Murine cytomegalovirus Immediate-early Antigens Mediate Protective Immunity,” Journal of Virology 61, no. 10 (1987): 3102-3108.

[187]

D. Wolf, H. Barreras, C. S. Bader, et al., “Marked in Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients After Hematopoietic Stem Cell Transplantation,” Biology of Blood and Marrow Transplantation 23, no. 5 (2017): 757-766.

[188]

Y. Meguri, T. Asano, T. Yoshioka, et al., “Responses of Regulatory and Effector T-cells to Low-dose Interleukin-2 Differ Depending on the Immune Environment After Allogeneic Stem Cell Transplantation,” Frontiers in immunology 13 (2022): 891925.

[189]

A. A. Kennedy-Nasser, S. Ku, P. Castillo-Caro, et al., “Ultra Low-dose IL-2 for GVHD Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation Mediates Expansion of Regulatory T Cells Without Diminishing Antiviral and Antileukemic Activity,” Clinical Cancer Research 20, no. 8 (2014): 2215-2225.

[190]

C. L. Mackall, T. J. Fry, C. Bare, P. Morgan, A. Galbraith, and R. E. Gress, “IL-7 Increases both Thymic-dependent and Thymic-independent T-cell Regeneration After Bone Marrow Transplantation,” Blood 97, no. 5 (2001): 1491-1497.

[191]

Y.-Y. Lei, X.-R. Chen, S. Jiang, et al., “Mechanisms of Thymic Repair of in Vitro-Induced Precursor T Cells as a Haploidentical Hematopoietic Stem Cell Transplantation Regimen,” Transplant Cell Ther 29, no. 6 (2023), https://doi.org/10.1016/j.jtct.2023.03.015.

[192]

A. Abdul-Hai, L. Weiss, A. Ben-Yehuda, D. Ergas, M. Y. Shapira, and S. Slavin, “Interleukin-7 Induced Facilitation of Immunological Reconstitution of Sublethally Irradiated Mice Following Treatment With Alloreactive Spleen Cells in a Murine Model of B-cell Leukemia/Lymphoma (BCL1),” Bone Marrow Transplantation 40, no. 9 (2007): 881-889.

[193]

A. E. C. Broers, S. J. Posthumus-van Sluijs, H. Spits, et al., “Interleukin-7 Improves T-cell Recovery After Experimental T-cell-depleted Bone Marrow Transplantation in T-cell-deficient Mice by Strong Expansion of Recent Thymic Emigrants,” Blood 102, no. 4 (2003): 1534-1540.

[194]

I. André-Schmutz, D. Bonhomme, F. Yates, et al., “IL-7 Effect on Immunological Reconstitution After HSCT Depends on MHC Incompatibility,” British Journal of Haematology 126, no. 6 (2004): 844-851.

[195]

M. A. Perales, J. D. Goldberg, J. Yuan, et al., “Recombinant human Interleukin-7 (CYT107) Promotes T-cell Recovery After Allogeneic Stem Cell Transplantation,” Blood 120, no. 24 (2012): 4882-4891.

[196]

D. M. Danilenko, “Preclinical and Early Clinical Development of Keratinocyte Growth Factor, an Epithelial-specific Tissue Growth Factor,” Toxicologic Pathology 27, no. 1 (1999): 64-71.

[197]

O. Alpdogan, V. M. Hubbard, O. M. Smith, et al., “Keratinocyte Growth Factor (KGF) Is Required for Postnatal Thymic Regeneration,” Blood 107, no. 6 (2006): 2453-2460.

[198]

Y. W. Chu, S. Schmitz, B. Choudhury, et al., “Exogenous Insulin-Like Growth Factor 1 Enhances Thymopoiesis Predominantly Through Thymic Epithelial Cell Expansion,” Blood 112, no. 7 (2008): 2836-2846.

[199]

C. Van Elssen and S. O. Ciurea, “NK Cell Therapy After Hematopoietic Stem Cell Transplantation: Can We Improve Anti-tumor Effect?,” International Journal of Hematology 107, no. 2 (2018): 151-156.

[200]

K. Rezvani, A. S. Yong, S. Mielke, et al., “Leukemia-associated Antigen-specific T-cell Responses Following Combined PR1 and WT1 Peptide Vaccination in Patients With Myeloid Malignancies,” Blood 111, no. 1 (2008): 236-242.

[201]

S. Naik, S. Vasileiou, I. Tzannou, et al., “Donor-derived Multiple Leukemia Antigen-specific T-cell Therapy to Prevent Relapse After Transplant in Patients With ALL,” Blood 139, no. 17 (2022): 2706-2711.

[202]

C. H. Yan, Q. F. Liu, D. P. Wu, et al., “Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-versus-Host Disease-Guided Multiple DLIs Could Improve Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Refractory/Relapsed Acute Leukemia,” Biology of Blood and Marrow Transplantation 23, no. 8 (2017): 1311-1319.

[203]

J. R. Passweg, A. Tichelli, S. Meyer-Monard, et al., “Purified Donor NK-lymphocyte Infusion to Consolidate Engraftment After Haploidentical Stem Cell Transplantation,” Leukemia 18, no. 11 (2004): 1835-1838.

[204]

S. Meyer-Monard, J. Passweg, U. Siegler, et al., “Clinical-grade Purification of Natural Killer Cells in Haploidentical Hematopoietic Stem Cell Transplantation,” Transfusion 49, no. 2 (2009): 362-371.

[205]

U. Koehl, R. Esser, S. Zimmermann, et al., “Ex Vivo Expansion of Highly Purified NK Cells for Immunotherapy After Haploidentical Stem Cell Transplantation in Children,” Klinische Padiatrie 217, no. 6 (2005): 345-350.

[206]

K.-H. Lee, S. R. Yoon, J.-R. Gong, et al., “The Infusion of Ex Vivo, Interleukin-15 and -21-activated Donor NK Cells After Haploidentical HCT in High-risk AML and MDS Patients-a Randomized Trial,” Leukemia 37, no. 4 (2023): 807-819.

[207]

S. Y. Lu, K. Y. Liu, D. H. Liu, L. P. Xu, and X. J. Huang, “High Frequencies of CD62L⁺ Naive Regulatory T Cells in Allografts Are Associated With a Low Risk of Acute Graft-versus-host Disease Following Unmanipulated Allogeneic Haematopoietic Stem Cell Transplantation,” Clinical and Experimental Immunology 165, no. 2 (2011): 264-277.

[208]

N. A. Jain, K. Lu, S. Ito, et al., “The Clinical and Financial Burden of Pre-emptive Management of cytomegalovirus Disease After Allogeneic Stem Cell Transplantation-implications for Preventative Treatment Approaches,” Cytotherapy 16, no. 7 (2014): 927-933.

[209]

S. R. Riddell, K. S. Watanabe, J. M. Goodrich, C. R. Li, M. E. Agha, and P. D. Greenberg, “Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones,” Science 257, no. 5067 (1992): 238-241.

[210]

T. Feuchtinger, K. Opherk, W. A. Bethge, et al., “Adoptive Transfer of pp65-specific T Cells for the Treatment of Chemorefractory cytomegalovirus Disease or Reactivation After Haploidentical and Matched Unrelated Stem Cell Transplantation,” Blood 116, no. 20 (2010): 4360-4367.

[211]

M. Odendahl, G. U. Grigoleit, H. Bönig, et al., “Clinical-scale Isolation of ‘Minimally Manipulated’ cytomegalovirus-specific Donor Lymphocytes for the Treatment of Refractory cytomegalovirus Disease,” Cytotherapy 16, no. 9 (2014): 1245-1256.

[212]

A. M. Leen, C. M. Bollard, A. M. Mendizabal, et al., “Multicenter Study of Banked Third-party Virus-specific T Cells to Treat Severe Viral Infections After Hematopoietic Stem Cell Transplantation,” Blood 121, no. 26 (2013): 5113-5123.

[213]

B. Withers, E. Blyth, L. E. Clancy, et al., “Long-term Control of Recurrent or Refractory Viral Infections After Allogeneic HSCT With Third-party Virus-specific T Cells,” Blood Adv 1, no. 24 (2017): 2193-2205.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

78

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/