Skip to main content
Top
Published in: Journal of Clinical Immunology 2/2012

01-04-2012

Immune Reconstitution Following Unmanipulated HLA-Mismatched/Haploidentical Transplantation Compared with HLA-Identical Sibling Transplantation

Authors: Ying-Jun Chang, Xiang-Yu Zhao, Ming-Rui Huo, Lan-Ping Xu, Dai-Hong Liu, Kai-Yan Liu, Xiao-Jun Huang

Published in: Journal of Clinical Immunology | Issue 2/2012

Login to get access

Abstract

In this study, we prospectively investigated the immune reconstitution in patients with hematological malignancies after human leukocyte antigen (HLA)-mismatched/unmanipulated haploidentical transplantation (50 cases) and HLA-matched transplant (25 cases). Transplant-related mortality, relapse, leukemia-free survival, and overall survival were similar between the two transplant strategies, although the cumulative incidence of CMV antigenemia was significantly higher in haploidentical recipients than in HLA-matched recipients (49.9 ± 7.2% versus 13 ± 7%, P = 0.007). Compared with HLA-matched recipients, T-cell subset and dendritic cell subgroup cell counts in the first 90 days after grafting were lower in haploidentical recipients. The difference was most striking for CD4+ and CD4+ naïve T cells. Reconstitution of B cells and monocytes was comparable between groups. T cells appeared equally functional in both groups among patients without graft-versus-host disease. Our results suggest that the clinical outcomes were not compromised by the early delayed immune reconstitution following haploidentical transplantation.
Literature
1.
go back to reference Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008;41:473–81.PubMedCrossRef Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008;41:473–81.PubMedCrossRef
2.
go back to reference Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–54.PubMedCrossRef Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–54.PubMedCrossRef
3.
go back to reference Huang XJ, Liu DH, Liu KY, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38:291–7.PubMedCrossRef Huang XJ, Liu DH, Liu KY, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38:291–7.PubMedCrossRef
4.
go back to reference Kang Y, Chao NJ, Aversa F. Unmanipulated or CD34 selected haplotype mismatched transplants. Curr Opin Hematol. 2008;15:561–7.PubMedCrossRef Kang Y, Chao NJ, Aversa F. Unmanipulated or CD34 selected haplotype mismatched transplants. Curr Opin Hematol. 2008;15:561–7.PubMedCrossRef
5.
go back to reference Lu DP, Dong L, Wu T, 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. 2006;107:3065–73.PubMedCrossRef Lu DP, Dong L, Wu T, 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. 2006;107:3065–73.PubMedCrossRef
6.
go back to reference Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.PubMedCrossRef Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.PubMedCrossRef
7.
go back to reference Shimazaki C, Ochiai N, Uchida R, et al. Non-T-cell-depleted HLA haploidentical stem cell transplantation in advanced hematologic malignancies based on the feto-maternal microchimerism. Blood. 2003;101:3334–6.PubMedCrossRef Shimazaki C, Ochiai N, Uchida R, et al. Non-T-cell-depleted HLA haploidentical stem cell transplantation in advanced hematologic malignancies based on the feto-maternal microchimerism. Blood. 2003;101:3334–6.PubMedCrossRef
8.
go back to reference van Rood JJ, Loberiza Jr FR, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood. 2002;99:1572–7.PubMedCrossRef van Rood JJ, Loberiza Jr FR, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood. 2002;99:1572–7.PubMedCrossRef
9.
go back to reference Ichinohe T, Uchiyama T, Shimazaki C, et al. Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism. Blood. 2004;104:3821–8.PubMedCrossRef Ichinohe T, Uchiyama T, Shimazaki C, et al. Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism. Blood. 2004;104:3821–8.PubMedCrossRef
10.
go back to reference Huang XJ, Chang YJ. Unmanipulated HLA-mismatched/haploidentical blood and marrow hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:197–204.PubMedCrossRef Huang XJ, Chang YJ. Unmanipulated HLA-mismatched/haploidentical blood and marrow hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:197–204.PubMedCrossRef
11.
go back to reference Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–93.PubMedCrossRef Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–93.PubMedCrossRef
12.
go back to reference Chang YJ, Zhao XY, Huo MR, et al. Influence of lymphocyte recovery on outcome of haploidentical transplantation for hematologic malignancies. Medicine (Baltimore). 2009;88:322–30.CrossRef Chang YJ, Zhao XY, Huo MR, et al. Influence of lymphocyte recovery on outcome of haploidentical transplantation for hematologic malignancies. Medicine (Baltimore). 2009;88:322–30.CrossRef
13.
go back to reference Porrata LF, Inwards DJ, Ansell SM, et al. Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study. Biol Blood Marrow Transplant. 2008;14:807–16.PubMedCrossRef Porrata LF, Inwards DJ, Ansell SM, et al. Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study. Biol Blood Marrow Transplant. 2008;14:807–16.PubMedCrossRef
14.
go back to reference Ishaqi MK, Afzal S, Dupuis A, et al. Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant. 2008;41:245–52.PubMedCrossRef Ishaqi MK, Afzal S, Dupuis A, et al. Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant. 2008;41:245–52.PubMedCrossRef
15.
go back to reference Hiwase DK, Hiwase S, Bailey M, et al. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2008;14:116–24.PubMedCrossRef Hiwase DK, Hiwase S, Bailey M, et al. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant. 2008;14:116–24.PubMedCrossRef
16.
go back to reference Xiao-Jun H, Lan-Ping X, Kai-Yan L, et al. HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase. Ann Med. 2008;40:444–55.PubMedCrossRef Xiao-Jun H, Lan-Ping X, Kai-Yan L, et al. HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase. Ann Med. 2008;40:444–55.PubMedCrossRef
17.
go back to reference Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.PubMedCrossRef Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.PubMedCrossRef
18.
go back to reference Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.PubMed Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.PubMed
19.
go back to reference Xiao-Jun H, Lan-Ping X, Kai-Yan L, et al. Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res. 2009;15:4777–83.PubMedCrossRef Xiao-Jun H, Lan-Ping X, Kai-Yan L, et al. Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res. 2009;15:4777–83.PubMedCrossRef
20.
go back to reference Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood. 2001;97:3380–9.PubMedCrossRef Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood. 2001;97:3380–9.PubMedCrossRef
21.
go back to reference Michie CA, McLean A, Alcock C, et al. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992;360:264–5.PubMedCrossRef Michie CA, McLean A, Alcock C, et al. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992;360:264–5.PubMedCrossRef
22.
go back to reference Chang YJ, Zhao XY, Huo MR, et al. Expression profiles of adhesion molecules on naive T cells in bone marrow grafts of healthy donors treated with granulocyte colony-stimulating factor. Transpl Immunol. 2009;21:228–33.PubMedCrossRef Chang YJ, Zhao XY, Huo MR, et al. Expression profiles of adhesion molecules on naive T cells in bone marrow grafts of healthy donors treated with granulocyte colony-stimulating factor. Transpl Immunol. 2009;21:228–33.PubMedCrossRef
23.
go back to reference Beckebaum S, Zhang X, Chen X, et al. Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets. Clin Cancer Res. 2004;10:7260–9.PubMedCrossRef Beckebaum S, Zhang X, Chen X, et al. Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets. Clin Cancer Res. 2004;10:7260–9.PubMedCrossRef
24.
go back to reference Chen H, Liu KY, Xu LP, et al. Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009;30:77–81.PubMed Chen H, Liu KY, Xu LP, et al. Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009;30:77–81.PubMed
25.
go back to reference Kim DH, Sohn SK, Won DI, et al. Rapid helper T-cell recovery above 200 × 10 6/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;37:1119–28.PubMedCrossRef Kim DH, Sohn SK, Won DI, et al. Rapid helper T-cell recovery above 200 × 10 6/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;37:1119–28.PubMedCrossRef
26.
go back to reference Koehl U, Bochennek K, Zimmermann SY, et al. Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+ CD3+ count reconstitution is associated with survival. Bone Marrow Transplant. 2007;39:269–78.PubMedCrossRef Koehl U, Bochennek K, Zimmermann SY, et al. Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+ CD3+ count reconstitution is associated with survival. Bone Marrow Transplant. 2007;39:269–78.PubMedCrossRef
27.
go back to reference Geddes M, Storek J. Immune reconstitution following hematopoietic stem-cell transplantation. Best Pract Res Clin Haematol. 2007;20:329–48.PubMedCrossRef Geddes M, Storek J. Immune reconstitution following hematopoietic stem-cell transplantation. Best Pract Res Clin Haematol. 2007;20:329–48.PubMedCrossRef
28.
go back to reference Storek J, Espino G, Dawson MA, et al. 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. 2000;96:3290–3.PubMed Storek J, Espino G, Dawson MA, et al. 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. 2000;96:3290–3.PubMed
29.
go back to reference Luo XH, Huang XJ, Liu KY, et al. Protective immunity transferred by infusion of cytomegalovirus-specific CD8(+) T cells within donor grafts: its associations with cytomegalovirus reactivation following unmanipulated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2010;16:994–1004.PubMedCrossRef Luo XH, Huang XJ, Liu KY, et al. Protective immunity transferred by infusion of cytomegalovirus-specific CD8(+) T cells within donor grafts: its associations with cytomegalovirus reactivation following unmanipulated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2010;16:994–1004.PubMedCrossRef
30.
go back to reference Casazza JP, Betts MR, Price DA, et al. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med. 2006;203:2865–77.PubMedCrossRef Casazza JP, Betts MR, Price DA, et al. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med. 2006;203:2865–77.PubMedCrossRef
31.
go back to reference Rissoan MC, Soumelis V, Kadowaki N, et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science. 1999;283:1183–6.PubMedCrossRef Rissoan MC, Soumelis V, Kadowaki N, et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science. 1999;283:1183–6.PubMedCrossRef
32.
go back to reference Porta MD, Rigolin GM, Alessandrino EP, et al. Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia: correlations with clinical and transplant characteristics. Eur J Haematol. 2004;72:18–25.PubMedCrossRef Porta MD, Rigolin GM, Alessandrino EP, et al. Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia: correlations with clinical and transplant characteristics. Eur J Haematol. 2004;72:18–25.PubMedCrossRef
33.
go back to reference Tanaka J, Asaka M, Imamura M. T-cell co-signalling molecules in graft-versus-host disease. Ann Hematol. 2000;79:283–90.PubMedCrossRef Tanaka J, Asaka M, Imamura M. T-cell co-signalling molecules in graft-versus-host disease. Ann Hematol. 2000;79:283–90.PubMedCrossRef
34.
go back to reference Harding FA, McArthur JG, Gross JA, et al. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992;356:607–9.PubMedCrossRef Harding FA, McArthur JG, Gross JA, et al. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992;356:607–9.PubMedCrossRef
35.
go back to reference Berger M, Figari O, Bruno B, et al. Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality. Bone Marrow Transplant. 2008;41:55–62.PubMedCrossRef Berger M, Figari O, Bruno B, et al. Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality. Bone Marrow Transplant. 2008;41:55–62.PubMedCrossRef
36.
go back to reference Afzal S, Ishaqi MK, Dupuis A, et al. Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia—update study. Bone Marrow Transplant. 2009;44:799–804.PubMedCrossRef Afzal S, Ishaqi MK, Dupuis A, et al. Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia—update study. Bone Marrow Transplant. 2009;44:799–804.PubMedCrossRef
37.
go back to reference Wang Y, Liu DH, Xu LP, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant. 2011;17:821–30.PubMedCrossRef Wang Y, Liu DH, Xu LP, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant. 2011;17:821–30.PubMedCrossRef
38.
go back to reference Passweg JR, Tichelli A, Meyer-Monard S, et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18:1835–8.PubMedCrossRef Passweg JR, Tichelli A, Meyer-Monard S, et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18:1835–8.PubMedCrossRef
39.
go back to reference Bao L, Dunham K, Stamer M, et al. Expansion of cytomegalovirus pp 65 and IE-1 specific cytotoxic T lymphocytes for cytomegalovirus-specific immunotherapy following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:1156–62.PubMedCrossRef Bao L, Dunham K, Stamer M, et al. Expansion of cytomegalovirus pp 65 and IE-1 specific cytotoxic T lymphocytes for cytomegalovirus-specific immunotherapy following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:1156–62.PubMedCrossRef
Metadata
Title
Immune Reconstitution Following Unmanipulated HLA-Mismatched/Haploidentical Transplantation Compared with HLA-Identical Sibling Transplantation
Authors
Ying-Jun Chang
Xiang-Yu Zhao
Ming-Rui Huo
Lan-Ping Xu
Dai-Hong Liu
Kai-Yan Liu
Xiao-Jun Huang
Publication date
01-04-2012
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 2/2012
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-011-9630-7

Other articles of this Issue 2/2012

Journal of Clinical Immunology 2/2012 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.