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.
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References
Rocha V, Gluckman E. Clinical use of umbilical cord blood hematopoietic stem cells. Biol Blood Marrow Transplant. 2006;12(1 Suppl 1):34–41.
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.
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.
Majhail NS, Brunstein CG, Wagner JE. Double umbilical cord blood transplantation. Curr Opin Immunol. 2006;18(5):571–5.
Brunstein CG, Setubal DC, Wagner JE. Expanding the role of umbilical cord blood transplantation. Br J Haematol. 2007;137(1):20–35.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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This study was supported by the Swedish Children’s Cancer Foundation PROJ08/013.
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Michael Uhlin and Jonas Mattsson, the senior investigators, contributed equally to the work.
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Berglund, S., Okas, M., Gertow, J. et al. Stable mixed donor–donor chimerism after double cord blood transplantation. Int J Hematol 90, 526–531 (2009). https://doi.org/10.1007/s12185-009-0398-y
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DOI: https://doi.org/10.1007/s12185-009-0398-y