Impact of Transplant-Related Complications on Lymphocyte Subset Reconstitution Following Allogeneic Hematopoietic Stem Cell Transplantation
DOI:
https://doi.org/10.14748/zy6fb656Keywords:
allogeneic hematopoietic stem cell transplantation, lymphocyte reconstitution, immune recovery, , transplant-related complications, graft-versus-host disease, infectionsAbstract
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a cornerstone treatment for hematologic malignancies, though frequently complicated by graft-versus-host disease (GVHD), infections, and immune dysregulation. The timely and effective recovery of lymphocyte subsets post-transplant is critical for long-term prognosis, yet remains poorly understood in the context of these complications.
Aim: The aim of this study was to evaluate the impact of transplant-related complications of the quantitative reconstitution of lymphocyte subsets in adult recipients of allogeneic hematopoietic stem cell transplantation.
Materials and Methods: This retrospective study analyzed 89 adult patients who underwent allo-HSCT at St. Marina University Hospital, Varna, between 2017 and 2023. Data on lymphocyte subset reconstitution (CD3⁺CD4⁺, CD3⁺CD8⁺CD38⁺, NK, and CD19⁺ cells) were collected at days +100, +180, and +270 post-transplant and correlated with the occurrence of transplant-related complications (GVHD, infections, relapse, and non-infectious complications). Various conditioning regimens and immunosuppressive protocols were applied, with most patients receiving HLA-matched or haploidentical grafts.
Results: Patients who experienced complications post-allo-HSCT exhibited significantly impaired immune recovery across all lymphocyte subsets. Graft-versus-host disease was the strongest negative predictor, associated with the lowest counts of CD3⁺CD4⁺ and CD3⁺CD8⁺CD38⁺ cells at all time points (p<0.001). Infectious complications also significantly reduced the reconstitution of CD4⁺, CD8⁺, NK, and B-cell populations (p<0.05).
Conclusion: Transplant-related complications, particularly GVHD and infections, substantially impair lymphocyte subset reconstitution following allo-HSCT, which may negatively impact clinical outcomes. Monitoring immune recovery dynamics provides prognostic insight and could inform individualized immunomodulatory strategies. These findings support the integration of immunological biomarkers into post-transplant risk stratification and patient management.
References
[1] Ji C, Dai R, Wu H, et al. Efficacy and safety of hematopoietic stem cell transplantation for hematologic malignancies. Medicine Case Reports and Study Protocols. 2021 Dec 1;2(12):e0174–4. doi: 10.1097/MD9.0000000000000174. DOI: https://doi.org/10.1097/MD9.0000000000000174
[2] Gyurkocza B, Rezvani A, Storb RF. Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol. 2010 Jun;3(3):285-99. doi: 10.1586/ehm.10.21. DOI: https://doi.org/10.1586/ehm.10.21
[3] Antin JH. Immune reconstitution: the major barrier to successful stem cell transplantation. Biol Blood Marrow Transplant. 2005 Feb;11(2 Suppl 2):43-5. doi: 10.1016/j.bbmt.2004.11.010. DOI: https://doi.org/10.1016/j.bbmt.2004.11.010
[4] Storek J, Geddes M, Khan F, et al. Reconstitution of the immune system after hematopoietic stem cell transplantation in humans. Semin Immunopathol. 2008 Dec 24;30(4):425–37. doi: 10.1007/s00281-008-0132-5. DOI: https://doi.org/10.1007/s00281-008-0132-5
[5] Servais S, Lengline E, Porcher R, et al. Long-Term Immune Reconstitution and Infection Burden after Mismatched Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2014 Apr;20(4):507-17. doi: 10.1016/j.bbmt.2014.01.001. DOI: https://doi.org/10.1016/j.bbmt.2014.01.001
[6] Naymagon S, Naymagon L, Wong SY, et al. Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol. 2017 Dec 27;14(12):711–26. doi: 10.1038/nrgastro.2017.126. DOI: https://doi.org/10.1038/nrgastro.2017.126
[7] Walz B, Maier C, Beck V. Treatment of graft versus host disease with methotrexate after allogeneic hematopoietic stem cell transplantation. J Dtsch Dermatol Ges. 2021 Jan;19(1):109-111. doi: 10.1111/ddg.14206. DOI: https://doi.org/10.1111/ddg.14206
[8] Kröger N, Shahnaz Syed Abd Kadir S, Zabelina T, et al. Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018 Oct;24(10):2152-2156. doi: 10.1016/j.bbmt.2018.05.023. DOI: https://doi.org/10.1016/j.bbmt.2018.05.023
[9] van der Waart AB, van der Velden WJFM, van Halteren AGS, et al. Decreased Levels of Circulating IL17-Producing CD161+CCR6+ T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation. PLoS One. 2012 Dec 4;7(12):e50896. doi: 10.1371/journal.pone.0050896. DOI: https://doi.org/10.1371/journal.pone.0050896
[10] Lin MT, Tseng LH, Frangoul H, et al. Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. Blood. 2000 Jun 15;95(12):3832–9. DOI: https://doi.org/10.1182/blood.V95.12.3832
[11] Naik S, Vasileiou S, Aguayo-Hiraldo P, et al. Toward Functional Immune Monitoring in Allogeneic Stem Cell Transplant Recipients. Biol Blood Marrow Transplant. 2020 May;26(5):911-9. doi: 10.1016/j.bbmt.2020.01.005. DOI: https://doi.org/10.1016/j.bbmt.2020.01.005
[12] Wils EJ, van der Holt B, Broers AEC, et al. Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. Haematologica. 2011 Dec 1;96(12):1846–54. doi: 10.3324/haematol.2011.047696. DOI: https://doi.org/10.3324/haematol.2011.047696
[13] Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood. 2001 Jun 1;97(11):3380–9. doi: 10.1182/blood.v97.11.3380. DOI: https://doi.org/10.1182/blood.V97.11.3380
[14] Ottinger H, Beelen D, Scheulen B. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood. 1996 Oct 1;88(7):2775–9. DOI: https://doi.org/10.1182/blood.V88.7.2775.bloodjournal8872775
[15] Talvensaari K, Clave E, Douay C, et al. A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation. Blood. 2002 Feb 15;99(4):1458–64. doi: 10.1182/blood.v99.4.1458. DOI: https://doi.org/10.1182/blood.V99.4.1458
[16] Massoud R, Gagelmann N, Fritzsche-Friedland U, 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. 2021 Apr 8;107(4):857–67. doi: 10.3324/haematol.2020.271445. DOI: https://doi.org/10.3324/haematol.2020.271445
[17] Toubert A, Glauzy S, Douay C. Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again. Tissue Antigens. 2012 Feb 6;79(2):83–9. doi: 10.1111/j.1399-0039.2011.01820.x. DOI: https://doi.org/10.1111/j.1399-0039.2011.01820.x
