Abstract
To investigate optimal unit selection for umbilical cord blood transplantation (UCBT), we conducted a registry-based study of 1355 adults with acute myeloid leukemia in first or second complete remission who underwent single-unit UCBT. To be eligible for analysis, UCB units had to contain a total nucleated cell (TNC) dose of 2.0 × 107/kg or higher and present at least a 4/6-match for HLA-A, -B, and -DR antigens in line with clinical practice in Japan, both of which are less stringent criteria than those used in Western countries. Neither TNC dose nor the degree of HLA matching affected survival (P = 0.138 and P = 0.696, respectively). As for HLA-A, -B antigens and -DRB1 allele, better HLA matching was associated with lower non-relapse mortality (P = 0.011) but higher relapse (P = 0.046), resulting in no improvement in survival (P = 0.680). Taking the allele level for each HLA-A, -B, and -DRB1 into consideration was less useful for predicting non-relapse mortality (P = 0.198). These findings suggest that the less stringent criteria for UCB unit selection are acceptable for Japanese patient population and perhaps even more beneficial in terms of providing a better chance to find a suitable UCB unit.
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References
Kekre N, Antin JH. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood. 2014;124:334–43.
Yanada M. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia during first complete remission: a clinical perspective. Int J Hematol. 2015;101:243–54.
Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med. 1998;339:1565–77.
Barker JN, Scaradavou A, Stevens CE. Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies. Blood. 2010;115:1843–9.
Cohen YC, Scaradavou A, Stevens CE, Rubinstein P, Gluckman E, Rocha V, et al. Factors affecting mortality following myeloablative cord blood transplantation in adults: a pooled analysis of three international registries. Bone Marrow Transpl. 2011;46:70–76.
Eapen M, Klein JP, Ruggeri A, Spellman S, Lee SJ, Anasetti C, et al. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood. 2014;123:133–40.
Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002;100:1611–8.
Barker JN, Byam C, Scaradavou A. How I treat: the selection and acquisition of unrelated cord blood grafts. Blood. 2011;117:2332–9.
Hough R, Danby R, Russell N, Marks D, Veys P, Shaw B, et al. Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols. Br J Haematol. 2016;172:360–70.
Barker JN, Kurtzberg J, Ballen K, Boo M, Brunstein C, Cutler C, et al. Optimal practices in unrelated donor cord blood transplantation for hematologic malignancies. Biol Blood Marrow Transpl. 2017;23:882–96.
Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW, et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol. 2004;32:397–407.
Kogler G, Enczmann J, Rocha V, Gluckman E, Wernet P. High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome. Bone Marrow Transpl. 2005;36:1033–41.
Arcese W, Rocha V, Labopin M, Sanz G, Iori AP, de Lima M, et al. Unrelated cord blood transplants in adults with hematologic malignancies. Haematologica. 2006;91:223–30.
Ooi J, Takahashi S, Tomonari A, Tsukada N, Konuma T, Kato S, et al. Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia. Biol Blood Marrow Transpl. 2008;14:1341–7.
Atsuta Y, Kanda J, Takanashi M, Morishima Y, Taniguchi S, Takahashi S, et al. Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica. 2013;98:814–22.
Sanz J, Jaramillo FJ, Planelles D, Montesinos P, Lorenzo I, Moscardo F, et al. Impact on outcomes of human leukocyte antigen matching by allele-level typing in adults with acute myeloid leukemia undergoing umbilical cord blood transplantation. Biol Blood Marrow Transpl. 2014;20:106–10.
Sobol U, Go A, Kliethermes S, Bufalino S, Rodriguez T, Smith S, et al. A prospective investigation of cell dose in single-unit umbilical cord blood transplantation for adults with high-risk hematologic malignancies. Bone Marrow Transpl. 2015;50:1519–25.
Konuma T, Kato S, Oiwa-Monna M, Tanoue S, Ogawa M, Isobe M, et al. Cryopreserved CD34(+) cell dose, but not total nucleated cell dose, influences hematopoietic recovery and extensive chronic graft-versus-host disease after single-unit cord blood transplantation in adult patients. Biol Blood Marrow Transpl. 2017;23:1142–50.
Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.
Atsuta Y. Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol. 2016;103:3–10.
Kanda J. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 2016;103:11–19.
Yanada M, Kanda J, Ohtake S, Fukuda T, Sakamaki H, Miyamura K, et al. Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission. Eur J Haematol. 2016;97:278–87.
Yanada M, Mori J, Aoki J, Harada K, Mizuno S, Uchida N, et al. Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients. Leuk Lymphoma. 2018;59:601–9.
Giralt S, Logan B, Rizzo D, Zhang MJ, Ballen K, Emmanouilides C, et al. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program. Biol Blood Marrow Transpl. 2007;13:844–52.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl. 2009;15:1628–33.
Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.
Activities and outcomes of hematopoietic cell transplantation in Japan (2016). http://www.jdchct.or.jp/en/data/slide/2016/ Accessed 21 Nov 2018.
Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C, et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol. 2011;12:1214–21.
Konuma T, Kato S, Ishii H, Takeda R, Oiwa-Monna M, Tojo A, et al. HLA-DRB1 mismatch is associated with a decreased relapse in adult acute myeloid leukemia after single-unit myeloablative cord blood transplantation. Ann Hematol. 2015;94:1233–5.
Kanda J, Morishima Y, Terakura S, Wake A, Uchida N, Takahashi S, et al. Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation. Leukemia. 2017;31:663–8.
Purtill D, Smith K, Devlin S, Meagher R, Tonon J, Lubin M, et al. Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by bank practice. Blood. 2014;124:2905–12.
Oran B, Cao K, Saliba RM, Rezvani K, de Lima M, Ahmed S, et al. Better allele-level matching improves transplant-related mortality after double cord blood transplantation. Haematologica. 2015;100:1361–70.
Brunstein CG, Petersdorf EW, DeFor TE, Noreen H, Maurer D, MacMillan ML, et al. Impact of allele-level HLA mismatch on outcomes in recipients of double umbilical cord blood transplantation. Biol Blood Marrow Transpl. 2016;22:487–92.
Oh H, Loberiza FR Jr., Zhang MJ, Ringden O, Akiyama H, Asai T, et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood. 2005;105:1408–16.
Morishima Y, Kawase T, Malkki M, Morishima S, Spellman S, Kashiwase K, et al. Significance of ethnicity in the risk of acute graft-versus-host disease and leukemia relapse after unrelated donor hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2013;19:1197–203.
Acknowledgements
This work was supported in part by a grant provided by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development (AMED) under the grant number 18ek0510023h0002.
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Yanada, M., Konuma, T., Kuwatsuka, Y. et al. Unit selection for umbilical cord blood transplantation for adults with acute myeloid leukemia in complete remission: a Japanese experience. Bone Marrow Transplant 54, 1789–1798 (2019). https://doi.org/10.1038/s41409-019-0539-8
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DOI: https://doi.org/10.1038/s41409-019-0539-8
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