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:

Cord blood transplantation: rewind to fast forward

Subjects

Abstract

The utilization of cord blood as a source of stem cells for transplantation has decreased in recent years. Although cord blood transplantation (CBT) is an established practice for the treatment of adult and pediatric patients with hematological malignancies, the high acquisition cost of CB units along with high transplant-related mortality due to delayed hematopoietic recovery and immune reconstitution have contributed to the slowing in widespread adoption of CBT. Strategies aimed to enhance speed of engraftment and ongoing clinical trials are investigating ways to make CBT more widely available. Meanwhile, the recent clinical data suggest that the choice of CBT might be preferable for patients with pre-transplant minimal residual disease. We review here the background data on the utilization of CB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of CBT.

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

Similar content being viewed by others

References

  1. Laughlin MJ, Barker J, Bambach B, Koc O, Rizzieri D, Wagner J 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  PubMed  Google Scholar 

  2. Laughlin MJ, Eapen M, Rubinstein P, Wagner J, Zhang M, Champlin R 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  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Kurtzberg J, Laughlin M, Graham M, Smith C, Olson J, Halperin E et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335: 157–166.

    Article  CAS  PubMed  Google Scholar 

  5. Barker J, Byam C, Kernan N, Lee S, Hawke R, Doshi K et al. Availability of cord blood extends allogeneic hematopoietic stem cell transplant access to racial and ethnic minorities. Biol Blood Marrow Transplant 2010; 16: 1541–1548.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014; 371: 339–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Eapen M, Rubinstein P, Zhang M, 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  PubMed  Google Scholar 

  8. Brunstein C, Gutman J, Weisdorf D, Woolfrey A, Defor T, Gooley T et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693–4699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Atsuta Y, Morishima Y, Suzuki R, Nagamura-Inoue T, Taniquchi S, Takahashi S et al. Comparison of unrelated cord blood transplantation and HLA-mismatched unrelated bone marrow transplantation for adults with leukemia. Biol Blood Marrow Transplant 2012; 18: 780–787.

    Article  PubMed  Google Scholar 

  10. Ponce D, Gonzales A, Lubin M, Castro-Malaspina H, Giralt S, Goldberg J et al. Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match. Biol Blood Marrow Transplant 2013; 19: 904–911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Newell L, Flowers M, Gooley T, Milano F, Carpenter P, Martin P et al. Characteristics of chronic GVHD after cord blood transplantation. Bone Marrow Transplant 2013; 48: 1285–1290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Broxmeyer H, Kurtzberg J, Gluckman E, Auerbach A, Douglas G, Cooper S et al. Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation. Blood Cells 1991; 17: 313–329.

    CAS  PubMed  Google Scholar 

  13. Broxmeyer HE, Hangoc G, Cooper S, Ribeiro R, Graves V, Yoder M et al. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci USA 1992; 89: 4109–4113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gluckman E, Broxmeyer H, Auerbach A, Friedman H, Douglas G, Devergie A et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1989; 321: 1174–1178.

    Article  CAS  PubMed  Google Scholar 

  15. Brunstein C, Fuchs E, Carter S, Karanes C, Costa L, Devine S et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 2011; 118: 282–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Majhail N, Mothukuri J, Brunstein C, Weisdorf D . Costs of hematopoietic cell transplantation: comparison of umbilical cord blood and matched related donor transplantation and the impact of posttransplant complications. Biol Blood Marrow Transplant 2009; 15: 564–573.

    Article  PubMed  Google Scholar 

  17. Barker J, Weisdorf D, DeFor T, Blazar B, McGlave P, Miller J 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  PubMed  Google Scholar 

  18. Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S et al. Pluripotent cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000; 6: 1278–1281.

    Article  CAS  PubMed  Google Scholar 

  19. Varnum-Finney B, Wu L, Yu M, Brashem-Stein C, Staats S, Flowers D et al. Immobilization of Notch ligand, Delta-1 is required for induction of notch signaling. J Cell Sci 2000; 113: 4313–4318.

    CAS  PubMed  Google Scholar 

  20. Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger R, Bernstein I . Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16: 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Milano F, Heimfeld S, Riffkin I, Nicoud I, Appelbaum F, Bernstein I et al. Infusion of a non HLA-matched off-the-shelf ex-vivo expanded cord blood progenitor cell product following myeloablative cord blood transplantation is safe, decreases the time to hematopoietic recovery, and results in excellent overall survival. Blood 2014; 124: 46.

    Google Scholar 

  22. Thompson P, Rezvani K, Hosing C, Oran B, Olson A, Popat U et al. Umbilical cord blood graft engineering: challenges and opportunities. Bone Marrow Transplant 2015; 50: S55–S62.

    Article  PubMed  Google Scholar 

  23. Ballen KK, Gluckman E, Broxmeyer HE . Umbilical cord blood transplantation: the first 25 years and beyond. Blood 2013; 122: 491–498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dahlberg A, Delaney C, Bernstein ID . ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 2011; 117: 6083–6090.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cutler C, Multani P, Robbins D, Kim H, Hoggat J, Pelus L et al. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 2013; 122: 3074–3081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Farag S, Srivastava S, Messina-Graham S, Schwartz J, Robertson M, Abonour R et al. In vivo DPP-4 inhibition to enhance engraftment of single-unit cord blood transplants in adults with hematological malignancies. Stem Cells Dev 2013; 22: 1007–1015.

    Article  CAS  PubMed  Google Scholar 

  27. Capitano M, Hangoc G, Cooper S, Broxmeyer H . Mild heat treatment primes human CD34+ cord blood cells for migration towards SDF-1α and enhances engraftment in an NSG mouse model. Stem Cells 2015; 33: 1975–1984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Popat U, Mehta R, Rezvani K, Fox P, Kondo K, Marin D et al. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood 2015; 125: 2885–2892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. de Lima M, McNiece I, Robinson S, Munsell M, Eapen M, Horowitz M et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med 2012; 367: 2305–2315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Horwitz M, Chao N, Rizzieri D, Long G, Sullivan K, Gasparetto C et al. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest 2014; 124: 3121–3128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Boitano A, Wang J, Romeo R, Bouchez L, Parker A, Sutton S et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010; 329: 1345–1348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wagner J, Brunstein C, Boitano A, DeFor T, McKenna D, Sumstad D et al. Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft. Cell Stem Cell 2016; 18: 144–155.

    Article  CAS  PubMed  Google Scholar 

  33. Wagner J, Eapen M, Carter S, Wang Y, Schultz K, Wall D et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 2014; 371: 1685–1694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Milano F, Gooley T, Wood B, Woolfrey A, Flowers M, Doney K et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med 2014; 375: 944–953.

    Article  Google Scholar 

  35. Verneris M, Brunstein C, Barker J, MacMillan M, Defor T, McKenna D et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009; 114: 4293–4299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sun J, Kurtzberg J . Cord blood for brain injury. Cytotherapy 2015; 17: 775–785.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F Milano.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dahlberg, A., Milano, F. Cord blood transplantation: rewind to fast forward. Bone Marrow Transplant 52, 799–802 (2017). https://doi.org/10.1038/bmt.2016.336

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.336

This article is cited by

Search

Quick links