Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Future of cord blood for oncology uses

Abstract

The utilization of umbilical cord blood (UCB) as a source of stem cells for transplantation has grown substantially in the last decade. Already an established practice for the treatment of children with hematological malignancies, its application for the treatment of adults is also expanding. The development of the double UCB and reduced-intensity transplantation platforms have contributed to this expansion. Recent registry-based analysis and ongoing single institution and multicenter clinical trials are investigating ways to make UCB transplantation more widely available. We review here the background data on the utilization of UCB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of UCB transplantation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Dew A, Collins D, Artz A, Rich E, Stock W, Swanson K et al. Paucity of HLA-identical unrelated donors for African-Americans with hematologic malignancies: the need for new donor options. Biol Blood Marrow Transplant 2008; 14: 938–941.

    Article  Google Scholar 

  2. 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: 1611–1618.

    CAS  PubMed  Google Scholar 

  3. Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E . Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet 1995; 346: 214–219.

    Article  CAS  Google Scholar 

  4. Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood 1996; 88: 795–802.

    CAS  PubMed  Google Scholar 

  5. Kurtzberg J, Graham M, Casey J, Olson J, Stevens CE, Rubinstein P . The use of umbilical cord blood in mismatched related and unrelated hemopoietic stem cell transplantation. Blood Cells 1994; 20: 275–283; discussion 284.

    CAS  PubMed  Google Scholar 

  6. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.

    Article  CAS  Google Scholar 

  7. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.

    CAS  PubMed  Google Scholar 

  8. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337: 373–381.

    Article  CAS  Google Scholar 

  9. 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: 2957–2961.

    Article  CAS  Google Scholar 

  10. Wall DA, Carter SL, Kernan NA, Kapoor N, Kamani NR, Brochstein JA et al. Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience. Biol Blood Marrow Transplant 2005; 11: 637–646.

    Article  CAS  Google Scholar 

  11. 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: 1565–1577.

    Article  CAS  Google Scholar 

  12. Jacobsohn DA, Hewlett B, Ranalli M, Seshadri R, Duerst R, Kletzel M . Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia. Bone Marrow Transplant 2004; 34: 901–907.

    Article  CAS  Google Scholar 

  13. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  Google Scholar 

  14. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  Google Scholar 

  15. Gluckman E, Rocha V . Donor selection for unrelated cord blood transplants. Curr Opin Immunol 2006; 18: 565–570.

    Article  CAS  Google Scholar 

  16. Rocha V, Wagner Jr JE, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med 2000; 342: 1846–1854.

    Article  CAS  Google Scholar 

  17. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  Google Scholar 

  18. Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 2001; 344: 1815–1822.

    Article  CAS  Google Scholar 

  19. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  Google Scholar 

  20. Eapen M, Rocha V, Scaradavou A, Gluckman E, Laughlin M, Stevens C et al. Effect of stem cell source on transplant outcomes in adult patients with acute leukemia: a comparison of unrelated bone marrow, peripheral blood, and cord blood. Blood 2008; 112: 62 (abstract 151).

    Google Scholar 

  21. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood 2004; 104: 3813–3820.

    Article  CAS  Google Scholar 

  22. 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: 1322–1330.

    Article  CAS  Google Scholar 

  23. Kumar P, Defor T, Brunstein C, Barker JN, Wagner JE, Weisdorf DJ et al. Allogeneic hematopoietic stem cell transplantation in adult acute lymphocytic leukemia:impact of donor source on survival. Biol Blood Marrow Transplant 2008; 14: 1394–1400.

    Article  Google Scholar 

  24. Brunstein CG, Barker JN, Weisdorf DJ, Defor T, McKenna D, Chong SY et al. Intra-Bone Marrow injection to enhance engraftment after myeloablative umbilical cord blood transplantation with 2 partially HLA-matched units. Bone Marrow Transplant 2008; 43: 935–940.

    Article  Google Scholar 

  25. Frassoni F, Gualandi F, Podesta M, Raiola AM, Ibatici A, Piaggio G et al. Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. Lancet Oncol 2008; 9: 831–839.

    Article  CAS  Google Scholar 

  26. Bautista G, Cabrera JR, Regidor C, Fores R, Garcia-Marco JA, Ojeda E et al. Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor. Bone Marrow Transplant 2008; 43: 365–373.

    Article  Google Scholar 

  27. Fernandez MN, Regidor C, Cabrera R, Garcia-Marco J, Briz M, Fores R et al. Cord blood transplants: early recovery of neutrophils from co-transplanted sibling haploidentical progenitor cells and lack of engraftment of cultured cord blood cells, as ascertained by analysis of DNA polymorphisms. Bone Marrow Transplant 2001; 28: 355–363.

    Article  CAS  Google Scholar 

  28. Fernandez MN, Regidor C, Cabrera R, Garcia-Marco JA, Fores R, Sanjuan I et al. Unrelated umbilical cord blood transplants in adults: early recovery of neutrophils by supportive co-transplantation of a low number of highly purified peripheral blood CD34+ cells from an HLA-haploidentical donor. Exp Hematol 2003; 31: 535–544.

    Article  Google Scholar 

  29. De Lima M, McMannis JD, Saliba R, Worth L, Kebriaei P, Popat U et al. Double cord transplantation with and without ex-vivo expansion. Blood 2008; 112: 63.

    Google Scholar 

  30. Delaney C, Brashen-Stein C, Voorhies H, Gutman J, Dallas M, Heimfeld S et al. Notch-mediated expansion of human cord blood progenitor cells results in rapid myeloid reconstitution in vivo following myeloablative cord blood transplantation. Blood 2008; 112: 85.

    Google Scholar 

  31. Delaney C, Varnum-Finney B, Aoyama K, Brashem-Stein C, Bernstein ID . Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and in vivo marrow repopulating ability of cord blood cells. Blood 2005; 106: 2693–2699.

    Article  CAS  Google Scholar 

  32. Broxmeyer HE, Kohli L, Kim CH, Lee Y, Mantel C, Cooper S et al. Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and G(alpha)i proteins and enhances engraftment of competitive, repopulating stem cells. J Leukoc Biol 2003; 73: 630–638.

    Article  CAS  Google Scholar 

  33. Broxmeyer HE, Hangoc G, Cooper S, Campbell T, Ito S, Mantel C . AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. Ann N Y Acad Sci 2007; 1106: 1–19.

    Article  CAS  Google Scholar 

  34. Ratajczak J, Reca R, Kucia M, Majka M, Allendorf DJ, Baran JT et al. Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood 2004; 103: 2071–2078.

    Article  CAS  Google Scholar 

  35. Ratajczak MZ, Reca R, Wysoczynski M, Kucia M, Baran JT, Allendorf DJ et al. Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells. Leukemia 2004; 18: 1482–1490.

    Article  CAS  Google Scholar 

  36. Wysoczynski M, Kucia M, Ratajczak J, Ratajczak MZ . Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis. Leukemia 2007; 21: 973–982.

    Article  CAS  Google Scholar 

  37. Jaffe ES, Harris NL, Vardiman JW . Tumors of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer: Lyon, 2001.

  38. 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: 3064–3070.

    Article  CAS  Google Scholar 

  39. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    Article  CAS  Google Scholar 

  40. 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: 82–89.

    Article  CAS  Google Scholar 

  41. Cutler C, Yeap B, Kao G, Ho V, Alyea E, Koreth J et al. Double umbilical cord blood transplantation sunig reduced intensity conditioning: a single-centre experience. Bone Marrow Transplant 2008; 41 (suppl 1): S23.

    Google Scholar 

  42. Rocha V, Rio B, Garnier F, Renaud M, Sirvent A, Takahashi S et al. Reduced intensity conditioning regimen in single unrelated cord blood transplantation in adults with hematological malignant disorders. An Eurocord-Netcord and SFGM-TC Survey. Blood 2006; 108: 897a.

    Google Scholar 

  43. Komatsu T, Narimatsu H, Yoshimi A, Kurita N, Kusakabe M, Hori A et al. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Ann Hematol 2006; 86: 49–54.

    Article  Google Scholar 

  44. Misawa M, Kai S, Okada M, Nakajima T, Nomura K, Wakae T et al. Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow. Int J Hematol 2006; 83: 74–79.

    Article  CAS  Google Scholar 

  45. Miyakoshi S, Yuji K, Kami M, Kusumi E, Kishi Y, Kobayashi K et al. Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases. Clin Cancer Res 2004; 10: 3586–3592.

    Article  Google Scholar 

  46. Morii T, Amano I, Tanaka H, Takahashi T, Kimura H . Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) in adult patients with high-risk hematological malignancies. Blood 2005; 106: 444b.

    Article  Google Scholar 

  47. Yuji K, Miyakoshi S, Kato D, Miura Y, Myojo T, Murashige N et al. Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma. Biol Blood Marrow Transplant 2005; 11: 314–318.

    Article  Google Scholar 

  48. Bradley MB, Satwani P, Baldinger L, Morris E, van de Ven C, Del Toro G et al. Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases. Bone Marrow Transplant 2007; 40: 621–631.

    Article  CAS  Google Scholar 

  49. Komatsu T, Narimatsu H, Yoshimi A, Kurita N, Kusakabe M, Hori A et al. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Ann Hematol 2007; 86: 49–54.

    Article  CAS  Google Scholar 

  50. Miyakoshi S, Kami M, Tanimoto T, Yamaguchi T, Narimatsu H, Kusumi E et al. Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases. Transplantation 2007; 84: 316–322.

    Article  CAS  Google Scholar 

  51. Narimatsu H, Watanabe M, Kohno A, Sugimoto K, Kuwatsuka Y, Uchida T et al. High incidence of graft failure in unrelated cord blood transplantation using a reduced-intensity preparative regimen consisting of fludarabine and melphalan. Bone Marrow Transplant 2008; 41: 753–756.

    Article  CAS  Google Scholar 

  52. Uchida N, Wake A, Takagi S, Yamamoto H, Kato D, Matsuhashi Y et al. Umbilical cord blood transplantation after reduced-intensity conditioning for elderly patients with hematologic diseases. Biol Blood Marrow Transplant 2008; 14: 583–590.

    Article  Google Scholar 

  53. Lim SH, Esler WV, Periman PO, Beggs D, Zhang Y, Townsend M . Reduced-intensity umbilical cord blood transplant for older adult patients. Bone Marrow Transplant 2008; 42: 685–686.

    Article  CAS  Google Scholar 

  54. Brunstein CG, Cantero S, Cao Q, Majhail N, McClune B, Burns LJ et al. Promising progression-free survival for patients low and intermediate grade lymphoid malignancies after nonmyeloablative umbilical cord blood transplantation. Biol Blood Marrow Transplant 2008; 15: 214–222.

    Article  Google Scholar 

  55. Brunstein CG, Setubal D, Tomblyn M, Defor T, Arora M, Burns L et al. Umbilical cord blood transplant after reduced intensity conditioning provides outcomes comparable HLA-matched siblings for patients with high risk and advanced acute myeloid leukemia. Blood 2006; 108: 183a.

    Article  Google Scholar 

  56. Rodrigues CA, Sanz G, Brunstein CG, Sanz J, Wagner JE, Renaud M et al. Analysis of risk factors for outcomes after unrelated cord blood transplantation in adults with lymphoid malignancies: a Study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2008; 27: 256–263.

    Article  Google Scholar 

  57. Wake A, Uchida N, Ishiwata K, Takagi S, Tsuji M, Yamamoto H et al. Single institute analysis of reduced intensity cord blood transplanatation from unrelated donors for adults with advanced lymphoid malignancies. Blood 2008; 112: 685.

    Google Scholar 

  58. Majhail NS, Brunstein CG, Tomblyn M, Thomas AJ, Miller JS, Arora M et al. Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor. Biol Blood Marrow Transplant 2008; 14: 282–289.

    Article  CAS  Google Scholar 

  59. 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: 1343–1347.

    Article  CAS  Google Scholar 

  60. 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: 1870–1871.

    Article  CAS  Google Scholar 

  61. Horwitz ME, Morris A, Gasparetto C, Sullivan K, Long G, Chute J et al. Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. Biol Blood Marrow Transplant 2008; 14: 591–594.

    Article  CAS  Google Scholar 

  62. Michalet M, Le QH, Robin M, Fegueux N, Furst S, Mohty M et al. Double cord blood cell hematopoietic stem cell transplantation after standard or reduced intensity conditioning: report of the SFGM-TC Registry. Blood 2008; 112: 688.

    Google Scholar 

  63. Gutman J, Leisenring W, Appelbaum FR, Woolfrey AE, Delaney C . Decreases relapse rates without excessive transplant related mortality following cord blood transplanatation: a matched cohort analysis comparing myeloablative cord, matched unrelated, and mismatched unrelated donor transplants. Blood 2008; 112: 356.

    Google Scholar 

  64. Kindwall-Keller TL, Hegerfeldt Y, Fu P, Lazarus HM, Cooper BW, Barr P et al. Prospective phase ii study of the biologic assigment one vs. two umbilical cord blood transplant in the reduced intensity conditioning setting. Blood 2008; 112: 684.

    Google Scholar 

  65. Brunstein CG, Weisdorf DJ, Defor T, Miller JS, McGlave PB, Blazar BR et al. Favorable leukemia-free survival (LFS) for adults and children undergoing myeloablative umbilical cord blood (UCB) transplantation with Cyclophosphamide (CY), fludarabine (FLU) and total body irradiation (TBI): a single center analysis of 194 patients. Blood 2008; 112: 682.

    Google Scholar 

  66. Verneris MR, Brunstein C, DeFor TE, Barker J, Weisdorf DJ, Blazar BR et al. Risk of relapse (REL) after umbilical cord blood transplantation (UCBT) in patients with acute leukemia: marked reduction in recipients of two units. Blood 2005; 106: 93a.

    Google Scholar 

  67. MacMillan M, Weisdorf DJ, Brunstein CG, Cao Q, Defor T, Verneris MR et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 2008; 113: 2410–2415.

    Article  Google Scholar 

  68. Willemze R, Rodrigues CA, Labopin M, Sanz G, Michel G, Socie G et al. KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 2009; 23: 492–500.

    Article  CAS  Google Scholar 

  69. Brunstein CG, Wagner JE, Weisdorf DJ, Cooley S, Noreen H, Barker J et al. Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplantation depends on transplantation conditioning intensity. Blood 2008; 112: 62.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C G Brunstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunstein, C., Weisdorf, D. Future of cord blood for oncology uses. Bone Marrow Transplant 44, 699–707 (2009). https://doi.org/10.1038/bmt.2009.286

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.286

Keywords

This article is cited by

Search

Quick links