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Published in: International Journal of Hematology 1/2015

01-01-2015 | Original Article

HLA Disparity is not crucial for the survival rate and severity of chronic health conditions in adult recipients following family donor hematopoietic stem cell transplantation

Authors: Meng Wang, Yu-Jun Dong, Zhi-Xiang Qiu, Mang-Ju Wang, Wei Liu, Li-Hong Wang, Yuan Li, Yu-Hua Sun, Wei-Lin Xu, Jin-Ping Ou, Wen-Sheng Wang, Ze-Yin Liang, Qian Wang, Xi-Nan Cen, Han-Yun Ren

Published in: International Journal of Hematology | Issue 1/2015

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Abstract

The shortage of HLA-identical siblings or unrelated donors has restricted the application of hematopoietic stem cell transplantation (HSCT). Few studies have systematically assessed survival and chronic health conditions (CHCs) in the same cohort of patients after HLA-mismatched/haploidentical (mismatched) family donor transplantation. In the present study, we retrospectively analyzed the survival of 127 adult patients receiving either HLA-matched (71 cases) or HLA-mismatched (56 cases) family donor transplantation. Of 127 patients, 81 patients survived at least 2 years after HSCT and were still alive until the present investigation. We evaluated the CHCs in 76 survivors (41 matched and 35 mismatched). CHC-related information was scored according to the Bone Marrow Transplant Survivor Study questionnaire. There was no significant difference in overall survival or disease-free survival between HLA-matched and -mismatched transplant recipients. The CHCs were less severe in HLA-mismatched recipients than in matched cohorts. Multivariate analysis identified that age over 40 years at transplantation and presence of chronic graft-versus-host disease were independent risk factors for CHCs, while anti-thymocyte globulin-containing conditioning regimens might be protective. However, HLA disparity was not crucial for either the survival rate or CHCs. In conclusion, HLA-mismatched family donor transplantation can achieve comparable therapeutic effects to HLA-identical sibling transplantation.
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Literature
1.
go back to reference Ljungman P, Bregni M, Brune M, European Group for Blood and Marrow Transplantation, et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010;45:219–34.PubMedCrossRef Ljungman P, Bregni M, Brune M, European Group for Blood and Marrow Transplantation, et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010;45:219–34.PubMedCrossRef
2.
go back to reference Rodriguez TE, Stiff PJ. Current treatment results of allogeneic bone marrow transplantation for acute myeloid and lymphoid leukemia. Curr Hematol Rep. 2003;2:295–301.PubMed Rodriguez TE, Stiff PJ. Current treatment results of allogeneic bone marrow transplantation for acute myeloid and lymphoid leukemia. Curr Hematol Rep. 2003;2:295–301.PubMed
3.
go back to reference Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007;110:3784–92.PubMedCentralPubMedCrossRef Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007;110:3784–92.PubMedCentralPubMedCrossRef
4.
go back to reference Bhatia S. Long-term health impacts of hematopoietic stem cell transplantation in form recommendations for follow-up. Expert Rev Hematol. 2011;4:437–54.PubMedCentralPubMedCrossRef Bhatia S. Long-term health impacts of hematopoietic stem cell transplantation in form recommendations for follow-up. Expert Rev Hematol. 2011;4:437–54.PubMedCentralPubMedCrossRef
5.
go back to reference Wong FL, Francisco L, Togawa K, et al. Long-term recovery after hematopoietic cell transplantation: predictors of quality of life concerns. Blood. 2010;115:2508–19.PubMedCentralPubMedCrossRef Wong FL, Francisco L, Togawa K, et al. Long-term recovery after hematopoietic cell transplantation: predictors of quality of life concerns. Blood. 2010;115:2508–19.PubMedCentralPubMedCrossRef
6.
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
7.
go back to reference Sun CL, Francisco L, Kawashima T, et al. Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood. 2010;116:3129–39.PubMedCentralPubMedCrossRef Sun CL, Francisco L, Kawashima T, et al. Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood. 2010;116:3129–39.PubMedCentralPubMedCrossRef
8.
go back to reference Sun CL, Francisco L, Baker KS, et al. Adverse psychological outcomes in long-term survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study (BMTSS). Blood. 2011;118:4723–31.PubMedCentralPubMedCrossRef Sun CL, Francisco L, Baker KS, et al. Adverse psychological outcomes in long-term survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study (BMTSS). Blood. 2011;118:4723–31.PubMedCentralPubMedCrossRef
9.
go back to reference Armenian SH, Sun CL, Kawashima T, et al. Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood. 2011;118:1413–20.PubMedCentralPubMedCrossRef Armenian SH, Sun CL, Kawashima T, et al. Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood. 2011;118:1413–20.PubMedCentralPubMedCrossRef
10.
go back to reference Mo XD, Xu LP, Liu DH, et al. Patients receiving HLA-haploidentical/partially matched related allo-HSCT can achieve desirable health-related QoL that is comparable to that of patients receiving HLA-identical sibling allo-HSCT. Bone Marrow Transplant. 2012;47:1201–5.PubMedCrossRef Mo XD, Xu LP, Liu DH, et al. Patients receiving HLA-haploidentical/partially matched related allo-HSCT can achieve desirable health-related QoL that is comparable to that of patients receiving HLA-identical sibling allo-HSCT. Bone Marrow Transplant. 2012;47:1201–5.PubMedCrossRef
11.
go back to reference Mertens AC, Ramsay NK, Kouris S, et al. Patterns of gonadal dysfunction following bone marrow transplantation. Bone Marrow Transplant. 1998;22:345–50.PubMedCrossRef Mertens AC, Ramsay NK, Kouris S, et al. Patterns of gonadal dysfunction following bone marrow transplantation. Bone Marrow Transplant. 1998;22:345–50.PubMedCrossRef
12.
go back to reference Bush N, Donaldson G, Moinpour C, et al. Development, feasibility and compliance of a web-based system for very frequent QOL and symptom home self-assessment after hematopoietic stem cell transplantation. Qual Life Res. 2005;14:77–93.PubMedCrossRef Bush N, Donaldson G, Moinpour C, et al. Development, feasibility and compliance of a web-based system for very frequent QOL and symptom home self-assessment after hematopoietic stem cell transplantation. Qual Life Res. 2005;14:77–93.PubMedCrossRef
13.
go back to reference Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–77.PubMed Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–77.PubMed
14.
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
16.
go back to reference Bieri S, Roosnek E, Helg C, et al. Quality of life and social integration after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2008;42:819–27.PubMedCrossRef Bieri S, Roosnek E, Helg C, et al. Quality of life and social integration after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2008;42:819–27.PubMedCrossRef
17.
go back to reference Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009;22:1041–50.PubMedCrossRef Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009;22:1041–50.PubMedCrossRef
18.
go back to reference Haynes L, Lefebvre JS. Age-related deficiencies in antigen-specific CD4 T cell responses: lessons from mouse models. Aging Dis. 2011;2:374–81.PubMedCentralPubMed Haynes L, Lefebvre JS. Age-related deficiencies in antigen-specific CD4 T cell responses: lessons from mouse models. Aging Dis. 2011;2:374–81.PubMedCentralPubMed
19.
go back to reference Hakim FT, Gress RE. Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007;70:179–89.PubMedCrossRef Hakim FT, Gress RE. Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007;70:179–89.PubMedCrossRef
20.
go back to reference Mitchell SA, Leidy NK, Mooney KH, et al. Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant. 2010;45:762–9.PubMedCentralPubMedCrossRef Mitchell SA, Leidy NK, Mooney KH, et al. Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant. 2010;45:762–9.PubMedCentralPubMedCrossRef
22.
go back to reference Baker KS, Fraser CJ. Quality of life and recovery after graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:333–41.PubMedCrossRef Baker KS, Fraser CJ. Quality of life and recovery after graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:333–41.PubMedCrossRef
23.
go back to reference Fraser CJ, Bhatia S, Ness K, et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. Blood. 2006;108:2867–73.PubMedCentralPubMedCrossRef Fraser CJ, Bhatia S, Ness K, et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. Blood. 2006;108:2867–73.PubMedCentralPubMedCrossRef
24.
go back to reference 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;117:4651–7.PubMedCentralPubMedCrossRef 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;117:4651–7.PubMedCentralPubMedCrossRef
25.
go back to reference Ratanatharathorn V, Ayash L, Lazarus HM, et al. Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant. 2001;28:121–9.PubMedCrossRef Ratanatharathorn V, Ayash L, Lazarus HM, et al. Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant. 2001;28:121–9.PubMedCrossRef
27.
go back to reference Socié G, Schmoor C, Bethge WA, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011;117:6375–82.PubMedCrossRef Socié G, Schmoor C, Bethge WA, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011;117:6375–82.PubMedCrossRef
28.
go back to reference Basara N, Baurmann H, Kolbe K, et al. Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group. Bone Marrow Transplant. 2005;35:1011–8.PubMedCrossRef Basara N, Baurmann H, Kolbe K, et al. Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group. Bone Marrow Transplant. 2005;35:1011–8.PubMedCrossRef
29.
go back to reference Pavletic SZ, Carter SL, Kernan NA, et al. Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation. Blood. 2005;106:3308–13.PubMedCentralPubMedCrossRef Pavletic SZ, Carter SL, Kernan NA, et al. Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation. Blood. 2005;106:3308–13.PubMedCentralPubMedCrossRef
30.
go back to reference Mohty M, Labopin M, Balère ML, et al. Antithymocyte globulins and chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Societé Française de Greffe de Moelle et de Therapie Cellulaire. Leukemia. 2010;24:1867–74.PubMedCrossRef Mohty M, Labopin M, Balère ML, et al. Antithymocyte globulins and chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Societé Française de Greffe de Moelle et de Therapie Cellulaire. Leukemia. 2010;24:1867–74.PubMedCrossRef
31.
go back to reference Duggan P, Booth K, Chaudhry A, et al. Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis. Bone Marrow Transplant. 2002;30:681–6.PubMedCrossRef Duggan P, Booth K, Chaudhry A, et al. Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis. Bone Marrow Transplant. 2002;30:681–6.PubMedCrossRef
32.
go back to reference Nachbaur D, Eibl B, Kropshofer G, et al. In vivo T cell depletion with low-dose rabbit antithymocyte globulin results in low transplant-related mortality and low relapse incidence following unrelated hematopoietic stem cell transplantation. J Hematother Stem Cell Res. 2002;11:731–7.PubMedCrossRef Nachbaur D, Eibl B, Kropshofer G, et al. In vivo T cell depletion with low-dose rabbit antithymocyte globulin results in low transplant-related mortality and low relapse incidence following unrelated hematopoietic stem cell transplantation. J Hematother Stem Cell Res. 2002;11:731–7.PubMedCrossRef
33.
go back to reference Ruzek MC, Waire JS, Hopkins D, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood. 2008;111:1726–34.PubMedCrossRef Ruzek MC, Waire JS, Hopkins D, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood. 2008;111:1726–34.PubMedCrossRef
35.
go back to reference Mohr B, Koch R, Thiede C, et al. CD34+ cell dose, conditioning regimen and prior chemotherapy : factors with significant impact on the early kinetics of donor chimerism after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2004;34:949–54.PubMedCrossRef Mohr B, Koch R, Thiede C, et al. CD34+ cell dose, conditioning regimen and prior chemotherapy : factors with significant impact on the early kinetics of donor chimerism after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2004;34:949–54.PubMedCrossRef
36.
go back to reference Bacigalupo A. Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis: efficacy and side effects. Bone Marrow Transplant. 2005;35:225–31.PubMedCrossRef Bacigalupo A. Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis: efficacy and side effects. Bone Marrow Transplant. 2005;35:225–31.PubMedCrossRef
38.
go back to reference Fehse N, Fehse B, Kroger N, et al. Influence of anti-thymocyte globulin as part of the conditioning regimen on immune reconstitution following matched related bone marrow transplantation. J Hematother Stem Cell Res. 2003;12:237–42.PubMedCrossRef Fehse N, Fehse B, Kroger N, et al. Influence of anti-thymocyte globulin as part of the conditioning regimen on immune reconstitution following matched related bone marrow transplantation. J Hematother Stem Cell Res. 2003;12:237–42.PubMedCrossRef
39.
go back to reference Bae KW, Kim BE, Koh KN, et al. Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children. Korean J Hematol. 2012;47:44–52.PubMedCentralPubMedCrossRef Bae KW, Kim BE, Koh KN, et al. Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children. Korean J Hematol. 2012;47:44–52.PubMedCentralPubMedCrossRef
40.
go back to reference Pan L, Delmonte J Jr, Jalonen CK, et al. Pretreatment of donor mice with granulocyte-colony stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood. 1995;86:4422–9.PubMed Pan L, Delmonte J Jr, Jalonen CK, et al. Pretreatment of donor mice with granulocyte-colony stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood. 1995;86:4422–9.PubMed
41.
go back to reference Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105:4120–6.PubMedCrossRef Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105:4120–6.PubMedCrossRef
Metadata
Title
HLA Disparity is not crucial for the survival rate and severity of chronic health conditions in adult recipients following family donor hematopoietic stem cell transplantation
Authors
Meng Wang
Yu-Jun Dong
Zhi-Xiang Qiu
Mang-Ju Wang
Wei Liu
Li-Hong Wang
Yuan Li
Yu-Hua Sun
Wei-Lin Xu
Jin-Ping Ou
Wen-Sheng Wang
Ze-Yin Liang
Qian Wang
Xi-Nan Cen
Han-Yun Ren
Publication date
01-01-2015
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2015
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-014-1691-y

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