Different Immune Reconstitution between Cord Blood and unrelated Bone Marrow Transplantation with Relation to Chronic Graft-versus-Host Disease
Background: Advances of allogeneic hematopoietic cell transplantation (allo-HCT) have brought long-term survival to the patients with hematologic malignancies. Chronic graft-versus-host disease (GVHD) is one of major problems for the long-survivors after allo-HCT. Dysregulation of immune reconstitution has been reported to be involved in the pathogenesis of chronic GVHD. Differences of immune reconstitution between cord blood transplantation (CBT) and unrelated bone marrow transplantation (uBMT) remain unclear in long-term survivors. We investigated immune reconstitution in patients who survive for more than 2 years after CBT (n=21) or uBMT (n=20) without relapse of underlying disease.
Materials and Methods: Using flowcytomeric analysis of peripheral blood, we investigated immune reconstitution of T cells, B cells, and NK cells between CBT and uBMT patients. We collected clinical data regarding allo-HCT and examined the relation of immune reconstitution to the development of chronic GVHD.
Results: Between CBT and uBMT patients, we found significant differences in absolute cell number of CD8+ as well as CD19+ cell and CD4/CD8 ratio even more than 2 years after allo-HCT. Among uBMT patients, absolute cell number of naïve CD4+ cell was significantly lower in patients with chronic GVHD. In addition, we found significant differences in absolute cell number of CD19+ cell, especially naïve B cell between patients with and without chronic GVHD in both CBT and uBMT patients.
Conclusion: These results suggest that differences of immune recovery between CBT and uBMT patients may exist even in patients who survive for more than 2 years and might be related to the development of chronic GVHD.
1. Kurosawa S, Oshima K, Yamaguchi T, et al. Quality of Life after Allogeneic Hematopoietic Cell Transplantation According to Affected Organ and Severity of Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017; 23(10):1749-1758.
2. Majhail NS. Long-term complications after hematopoietic cell transplantation. Hematol Oncol Stem Cell Ther. 2017; 10(4):220-227.
3. Pidala J, Kurland B, Chai X, et al. Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium. Blood. 2011; 117(17):4651-4657.
4. Sobocinski KA, Arora M, Horowitz MH, et al. Relapse and Late Mortality in 5-Year Survivors of Myeloablative Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia in First Chronic Phase. J Clin Oncol. 28(11):1888-1895.
5. Martin PJ, Counts Jr GW, et al. Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol. 28(6):1011-1016.
6. Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11):3214-3219.
7. Kanda J, Nakasone H, Atsuta Y, et al. Risk factors and organ involvement of chronic GVHD in Japan. Bone Marrow Transplant. 2014; 49(2):228-35.
8. Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood. 2014; 124(3):374-384.
9. Zeiser R, Sarantopoulos S, Blazar BR. B-cell targeting in chronic graft-versus-host disease. Blood. 2018; 131(13):1399-1405.
10. Alho AC, Kim HT, Chammas MJ, et al. Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Blood. 2016; 127(5):646-657.
11. Khoder A, Sarvaria A, Alsuliman A, et al. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood. 2014; 124(13):2034-2045.
12. Jacobson CA, Turki AT, McDonough SM, et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2012; 18(4):565-74.
13. Kanda J, Chiou LW, Szabolcs P, et al. Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012; 18(11):1664-1676.
14. Bejanyan N, Brunstein CG, Cao Q, et al. Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv. 2018; 2(8):909-922.
15. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3):389-401.
16. Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006; 203(7):1701-11.
17. Brown JA, Stevenson K, Kim HT, et al. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood. 2010; 115(20):4111-9.
18. Ballen K, Woo Ahn K, Chen M, et al. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016; 22(9):1636-1645.
19. de Masson A, Bouaziz JD, Le Buanec H, et al. CD24 (hi) CD27⁺ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease. Blood. 2015; 125(11):1830-9.
20. Wilke C, Holtan SG, Sharkey L, et al. Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen. Radiother Oncol. 2016; 118(1):65-71.
21. Geyer MB, Jacobson JS, Freedman J, et al. A comparison of immune reconstitution and graft-versus-host disease following myeloablative conditioning versus reduced toxicity conditioning and umbilical cord blood transplantation in paediatric recipients. Br J Haematol. 2011; 155(2):218-34.
22. Li X, Gao Q, Feng Y, et al. Developing role of B cells in the pathogenesis and treatment of chronic GVHD. Br J Haematol. 2019; 184(3):323-336.
23. Sarantopoulos S, Blazar BR, Cutler C, et al. B cells in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015; 21(1):16-23.
24. MacDonald KP, Hill GR, Blazar BR. Chronic graft-versus-host disease: biological insights from preclinical and clinical studies. Blood. 2017; 129(1):13-21.
25. Cutler CS, Koreth J, Ritz J. Mechanistic approaches for the prevention and treatment of chronic GVHD. Blood. 2017; 129(1):22-29.
26. Nakasone H, Sahaf B, Miklos DB. Therapeutic benefits targeting B-cells in chronic graft-versus-host disease. Int J Hematol. 2015; 101(5):438-51.
27. Koreth J, Kim HT, Jones KT, et al. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease. Blood. 2016; 128(1):130-7.
28. Kharfan-Dabaja, Cutler CS. Rituximab for prevention and treatment of graft-versus-host disease. Int J Hematol. 2011; 93(5):578-585.
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