Skip to main content
Top
Published in: International Journal of Hematology 4/2009

01-11-2009 | Original Article

Stable mixed donor–donor chimerism after double cord blood transplantation

Authors: Sofia Berglund, Mantas Okas, Jens Gertow, Michael Uhlin, Jonas Mattsson

Published in: International Journal of Hematology | Issue 4/2009

Login to get access

Abstract

Double cord blood transplantation (DCBT) has been used increasingly and has proven to be both safe and efficacious. In chimerism analysis, previous studies have indicated single unit predominance early after DCBT. In the present study, we evaluated the chimeric pattern in T-, B- and myeloid cells using PCR-based chimerism analysis in seven patients after DCBT: five patients had acute leukemia and two had lymphoma. Five patients received myeloablative conditioning and two patients were given reduced intensity conditioning. All patients received anti-thymocyte globulin (ATG) before DCBT. Three of the six evaluable patients showed donor–donor mixed chimerism in all cell lineages at 90 days after DCBT. Interestingly, two patients in long-term follow-up showed mixed donor chimerism in all cell lineages at 25 and 35 months after DCBT, respectively. Both patients are doing clinically well. Neither of the two developed GVHD after DCBT. In conclusion, in this study donor–donor mixed chimerism was common after high dose ATG and DCBT. Further studies are warranted concerning the immunological consequences of the phenomenon of donor–donor mixed chimerism after DCBT.
Literature
1.
go back to reference Rocha V, Gluckman E. Clinical use of umbilical cord blood hematopoietic stem cells. Biol Blood Marrow Transplant. 2006;12(1 Suppl 1):34–41.CrossRefPubMed Rocha V, Gluckman E. Clinical use of umbilical cord blood hematopoietic stem cells. Biol Blood Marrow Transplant. 2006;12(1 Suppl 1):34–41.CrossRefPubMed
2.
go back to reference Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant. 2007;13(4):444–53.CrossRefPubMed Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant. 2007;13(4):444–53.CrossRefPubMed
3.
go back to reference Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood. 2007;109(3):1322–30.CrossRefPubMed Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood. 2007;109(3):1322–30.CrossRefPubMed
4.
go back to reference Majhail NS, Brunstein CG, Wagner JE. Double umbilical cord blood transplantation. Curr Opin Immunol. 2006;18(5):571–5.CrossRefPubMed Majhail NS, Brunstein CG, Wagner JE. Double umbilical cord blood transplantation. Curr Opin Immunol. 2006;18(5):571–5.CrossRefPubMed
5.
go back to reference Brunstein CG, Setubal DC, Wagner JE. Expanding the role of umbilical cord blood transplantation. Br J Haematol. 2007;137(1):20–35.CrossRefPubMed Brunstein CG, Setubal DC, Wagner JE. Expanding the role of umbilical cord blood transplantation. Br J Haematol. 2007;137(1):20–35.CrossRefPubMed
6.
go back to reference Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E, et al. Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transplant. 2007;13(1):82–9.CrossRefPubMedPubMedCentral Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E, et al. Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transplant. 2007;13(1):82–9.CrossRefPubMedPubMedCentral
7.
go back to reference Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005;105(3):1343–7.CrossRefPubMed Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005;105(3):1343–7.CrossRefPubMed
8.
go back to reference Barker JN, Weisdorf DJ, Wagner JE. Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med. 2001;344(24):1870–1.CrossRefPubMed Barker JN, Weisdorf DJ, Wagner JE. Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med. 2001;344(24):1870–1.CrossRefPubMed
9.
go back to reference Mattsson J, Uzunel M, Brune M, Hentschke P, Barkholt L, Stierner U, et al. Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol. 2001;115(4):935–44.CrossRefPubMed Mattsson J, Uzunel M, Brune M, Hentschke P, Barkholt L, Stierner U, et al. Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol. 2001;115(4):935–44.CrossRefPubMed
10.
go back to reference Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood. 2007;110(8):3064–70.CrossRefPubMedPubMedCentral Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood. 2007;110(8):3064–70.CrossRefPubMedPubMedCentral
11.
go back to reference Uzunel M, Remberger M, Sairafi D, Hassan Z, Mattsson J, Omazic B, et al. Unrelated versus related allogeneic stem cell transplantation after reduced intensity conditioning. Transplantation. 2006;82(7):913–9.CrossRefPubMed Uzunel M, Remberger M, Sairafi D, Hassan Z, Mattsson J, Omazic B, et al. Unrelated versus related allogeneic stem cell transplantation after reduced intensity conditioning. Transplantation. 2006;82(7):913–9.CrossRefPubMed
12.
go back to reference Schaffer M, Aldener-Cannava A, Remberger M, Ringden O, Olerup O. Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation. Tissue Antigens. 2003;62(3):243–50.CrossRefPubMed Schaffer M, Aldener-Cannava A, Remberger M, Ringden O, Olerup O. Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation. Tissue Antigens. 2003;62(3):243–50.CrossRefPubMed
13.
go back to reference Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295–304.CrossRefPubMed Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295–304.CrossRefPubMed
14.
go back to reference Svahn BM, Remberger M, Myrback KE, Holmberg K, Eriksson B, Hentschke P, et al. Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood. 2002;100(13):4317–24.CrossRefPubMed Svahn BM, Remberger M, Myrback KE, Holmberg K, Eriksson B, Hentschke P, et al. Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood. 2002;100(13):4317–24.CrossRefPubMed
15.
go back to reference Mattsson J, Uzunel M, Tammik L, Aschan J, Ringden O. Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation. Leukemia. 2001;15(12):1976–85.CrossRefPubMed Mattsson J, Uzunel M, Tammik L, Aschan J, Ringden O. Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation. Leukemia. 2001;15(12):1976–85.CrossRefPubMed
16.
go back to reference Winiarski J, Mattsson J, Gustafsson A, Wester D, Borgstrom B, Ringden O, et al. Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation. Pediatr Transplant. 1998;2(2):150–6.PubMed Winiarski J, Mattsson J, Gustafsson A, Wester D, Borgstrom B, Ringden O, et al. Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation. Pediatr Transplant. 1998;2(2):150–6.PubMed
17.
go back to reference Ringden O, Okas M, Uhlin M, Uzunel M, Remberger M, Mattsson J. Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. Bone Marrow Transplant. 2008;42(10):643–8.CrossRefPubMed Ringden O, Okas M, Uhlin M, Uzunel M, Remberger M, Mattsson J. Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. Bone Marrow Transplant. 2008;42(10):643–8.CrossRefPubMed
18.
go back to reference Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood. 2001;97(10):2957–61.CrossRefPubMed Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood. 2001;97(10):2957–61.CrossRefPubMed
19.
go back to reference Kang HJ, Kho SH, Jang MK, Lee SH, Shin HY, Ahn HS. Early engraftment kinetics of two units cord blood transplantation. Bone Marrow Transplant. 2006;38(3):197–201.CrossRefPubMed Kang HJ, Kho SH, Jang MK, Lee SH, Shin HY, Ahn HS. Early engraftment kinetics of two units cord blood transplantation. Bone Marrow Transplant. 2006;38(3):197–201.CrossRefPubMed
20.
go back to reference De Lima M, St John LS, Wieder ED, Lee MS, McMannis J, Karandish S, et al. Double-chimerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. Br J Haematol. 2002;119(3):773–6.CrossRefPubMed De Lima M, St John LS, Wieder ED, Lee MS, McMannis J, Karandish S, et al. Double-chimerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. Br J Haematol. 2002;119(3):773–6.CrossRefPubMed
21.
go back to reference Haspel RL, Kao G, Yeap BY, Cutler C, Soiffer RJ, Alyea EP, et al. Preinfusion variables predict the predominant unit in the setting of reduced-intensity double cord blood transplantation. Bone Marrow Transplant. 2008;41(6):523–9.CrossRefPubMed Haspel RL, Kao G, Yeap BY, Cutler C, Soiffer RJ, Alyea EP, et al. Preinfusion variables predict the predominant unit in the setting of reduced-intensity double cord blood transplantation. Bone Marrow Transplant. 2008;41(6):523–9.CrossRefPubMed
22.
go back to reference Yen HJ, Chiou TJ, Hung GY, Chang CY, Hsieh MY, Tzeng CH, et al. Long-term mixed full-donor chimerism with dominance reversion after a double-unit cord blood transplant. Eur J Haematol. 2008;80(4):366–7.CrossRefPubMed Yen HJ, Chiou TJ, Hung GY, Chang CY, Hsieh MY, Tzeng CH, et al. Long-term mixed full-donor chimerism with dominance reversion after a double-unit cord blood transplant. Eur J Haematol. 2008;80(4):366–7.CrossRefPubMed
23.
go back to reference Jaksch M, Uzunel M, Remberger M, Sundberg B, Mattsson J. Molecular monitoring of T-cell chimerism early after allogeneic stem cell transplantation may predict the occurrence of acute GVHD grades II–IV. Clin Transplant. 2005;19(3):346–9.CrossRefPubMed Jaksch M, Uzunel M, Remberger M, Sundberg B, Mattsson J. Molecular monitoring of T-cell chimerism early after allogeneic stem cell transplantation may predict the occurrence of acute GVHD grades II–IV. Clin Transplant. 2005;19(3):346–9.CrossRefPubMed
24.
go back to reference Mattsson J, Uzunel M, Remberger M, Ringden O. T-cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Transplantation. 2001;71(3):433–9.CrossRefPubMed Mattsson J, Uzunel M, Remberger M, Ringden O. T-cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Transplantation. 2001;71(3):433–9.CrossRefPubMed
25.
go back to reference Remberger M, Svahn BM, Mattsson J, Ringden O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004;78(1):122–7.PubMed Remberger M, Svahn BM, Mattsson J, Ringden O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004;78(1):122–7.PubMed
26.
go back to reference Remberger M, Mattsson J, Svahn BM, Ringden O. Using reduced intensity conditioning and HLA-identical sibling donors, antithymocyte globulin increases the risk of relapse, which can be overcome by a high stem cell dose. Bone Marrow Transplant. 2008;42(11):769–71.CrossRefPubMed Remberger M, Mattsson J, Svahn BM, Ringden O. Using reduced intensity conditioning and HLA-identical sibling donors, antithymocyte globulin increases the risk of relapse, which can be overcome by a high stem cell dose. Bone Marrow Transplant. 2008;42(11):769–71.CrossRefPubMed
27.
go back to reference Ildstad ST, Wren SM, Bluestone JA, Barbieri SA, Stephany D. Effect of selective T-cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2–B10). J Immunol. 1986;136(1):28–33.PubMed Ildstad ST, Wren SM, Bluestone JA, Barbieri SA, Stephany D. Effect of selective T-cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2–B10). J Immunol. 1986;136(1):28–33.PubMed
Metadata
Title
Stable mixed donor–donor chimerism after double cord blood transplantation
Authors
Sofia Berglund
Mantas Okas
Jens Gertow
Michael Uhlin
Jonas Mattsson
Publication date
01-11-2009
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 4/2009
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0398-y

Other articles of this Issue 4/2009

International Journal of Hematology 4/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine