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:

The great debate: haploidentical or cord blood transplant

Abstract

One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to 75% of patients who do not have an HLA-matched sibling donor. A substantial proportion of the need has been met by HLA-matched volunteer unrelated donors, but an unmet need still exists, particularly among minority populations and for people who need a more immediate source of hematopoietic cells. Two such sources, umbilical cord blood (UCB) and haploidentical related donors, have filled most of this need, and outcomes following transplants from these donor sources are very promising. UCB has the advantages of ready availability and is less capable of causing GVHD but hematological recovery and immune reconstitution are slow. Haploidentical HCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post transplant cellular immunotherapy, but is complicated by a high risk of GVHD and poor immune reconstitution when GVHD is prevented by vigorous ex vivo or in vivo T-cell depletion. This review will discuss the pertinent issues that affect the choice of one donor source over another and offer recommendations regarding the optimal utilization of these donor sources.

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

Similar content being viewed by others

References

  1. Laughlin MJ, Barker J, Bambach B, Roc 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  PubMed  Google Scholar 

  2. Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Olwa-Monna M et al. Comparative single-institute analysis of cord blood transplantation from related 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  PubMed  Google Scholar 

  3. 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 myelogeneous leukemia. Biol Blood Marrow Transplant 2008; 14: 1341–1347.

    Article  CAS  PubMed  Google Scholar 

  4. Sanz J, Sanz MA, Saavedra S, Lorenzo J, Montesinos P, Senent L et al. Cord blood transplantation from unrelated donors in adults with high-risk acute myeloid leukemia. Biol Blood Marrow Transplant 2010; 16: 86–94.

    Article  PubMed  Google Scholar 

  5. Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W et al. Effect of graft source of unrelated donor hematopoietic stem-cell transplantation in adults with acute leukemia: a retrospective analysis. Lancet 2010; 11: 653–660.

    Article  Google Scholar 

  6. Uchida N, Wake A, Takagi S, Yamamoto H, Matsuhashi Y, Matsumura J 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  PubMed  Google Scholar 

  7. Rocha V, Mohty M, Gluckman E, Rio B . Reduced-intensity conditioning regimens before unrelated cord blood transplantation in adults with acute leukemia and other hematologic malignancies. Curr Opin Oncol 2009; 21: 531–534.

    Article  Google Scholar 

  8. 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  PubMed  Google Scholar 

  9. Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH 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 

  10. 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  PubMed  PubMed Central  Google Scholar 

  11. 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  PubMed  PubMed Central  Google Scholar 

  12. Cutler C, Stevenson K, Kim HT, Brown J, McDonough S, Herrera M et al. Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant 2011; 46: 273–277.

    Article  Google Scholar 

  13. Brown JA, Stevenson K, Kim HT, Cutler C, Ballen K, McDonough S et al. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood 2010; 115: 4111–4119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rocha V, Gluckman E . Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft-and transplantation-related factors. Br J Hematol 2009; 147: 262–274.

    Article  CAS  Google Scholar 

  15. Matsumo N, Wake A, Uchida N, Ishiwata K, Aroaka H, Takagi S et al. Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation. Blood 2009; 114: 1689–1695.

    Article  Google Scholar 

  16. van Rood JJ, Stevens CE, Smits J, Carrier C, Carpenter C, Scaradavou A . Reexposure of cord blood to noninherited maternal HLA antigens improves transplant outcomes in hematologic malignancies. Proc Natl Acad Sci USA 2009; 106: 19952–19957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. de Lima M, McMannis J, Gee A, Kkomanduri K, Couriel D, Andersson BS et al. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraehylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant 2008; 41: 771–778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dey BR, Spitzer TR . Current status of haploidentical stem cell transplantation. Br J Haematol 2006; 135: 423–437.

    Article  PubMed  Google Scholar 

  20. Aversa F, Reisner Y, Martelli MF . The haploidentical option high-risk hematologic malignancies. Blood Cells Mol Dis 2008; 40: 8–12.

    Article  PubMed  Google Scholar 

  21. Fuchs EJ, Huang XJ, Miller JS . HLA-haploidentical stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2010; 16 (Suppl 1): 557–563.

    Google Scholar 

  22. Truit RL, Rimm AA, Saltzstein EC, Rose WC, Bortin MM . Graft- vs-leukemia for AKR spontaneous leukemia-lymphoma. Transplant Proc 1976; 8: 569–574.

    Google Scholar 

  23. Drobyski WR, Klein J, Flomenberg N, Pietryoga D, Vesole DH, Margolis DA et al. Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood 2002; 99: 806–814.

    Article  CAS  PubMed  Google Scholar 

  24. Burroughs LM, O′Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 1279–1287.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Powles RL, Morgenstern GR, Kay HE . Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. Lancet 1983; 1: 612–615.

    Article  CAS  PubMed  Google Scholar 

  26. Beatty PG, Cliff RA, Mickelson EM . Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765–771.

    Article  CAS  PubMed  Google Scholar 

  27. Spitzer TR, McAfee SL, Dey BR, Colby C, Hope J, Grossberg H et al Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies. Transplantation 2003; 75: 1748–1751.

    Article  CAS  PubMed  Google Scholar 

  28. Mehta J, Singhai S, Gee AP, Chang KY, Godder K, van Rhee F et al. Bone marrow transplantation from partially HLA-mismatched donors for acute leukemia: single center experience of 201 patients. Bone Marrow Transplant 2004; 33: 389–397.

    Article  CAS  PubMed  Google Scholar 

  29. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study inpatients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23: 3447–3454.

    Article  PubMed  Google Scholar 

  30. Rizzieri DA, Koh LP, Long GD, Gasparetto C, Sullivan KM, Horwitz M et al. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol 2007; 25: 690–697.

    Article  CAS  PubMed  Google Scholar 

  31. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W et al. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant 2009; 15: 257–265.

    Article  CAS  PubMed  Google Scholar 

  33. Ruggeri L, Capanni M, Urbani E, Perruccio K, Schlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    Article  CAS  PubMed  Google Scholar 

  34. Symons HJ, Leffell MS, Rossiter ND, Zahurak M, Jones RJ, Fuchs EJ . Improved survival with inhibitory killer immunoglobulin receptor (KIR) gene mismatches and KIR haplotype B donors after nonmyeloablative HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant 2010; 16: 533–542.

    Article  PubMed  Google Scholar 

  35. van Rood JJ, Loberiza Jr FR, Zhang MJ, Oudshoorn M, Claas MS, Champlin RE et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood 2002; 99: 1572–1577.

    Article  PubMed  Google Scholar 

  36. Stern M, Ruggeri L, Mancusi A, Bernardo ME, de Angelis C, Bucher C et al. Survival after T-cell depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood 2008; 112: 2990–2995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ et al High risk of graft failure in patients with HLA-antibodies undergoing haploidentical stem-cell transplantation. Transplantation 2009; 88: 1019–1024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood 2007; 110: 2764–2767.

    Article  CAS  PubMed  Google Scholar 

  39. Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006; 108: 1797–1798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dodero A, Carniti C, Raganato A, Vendramin A, Farina L, Spina F et al. Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improved T-cell recovery. Blood 2009; 113: 4771–4779.

    Article  CAS  PubMed  Google Scholar 

  41. Yoon SR, Hee YS, Yang SH . Generation of donor natural killer cells from CD34+ progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study. Bone Marrow Transplant 2010; 45: 1038–1046.

    Article  CAS  PubMed  Google Scholar 

  42. Ciceri F, Labopin M, Aversa F, Rowe JM, Bunies D, Lewalle P et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood 2008; 112: 3574–3581.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K K Ballen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ballen, K., Spitzer, T. The great debate: haploidentical or cord blood transplant. Bone Marrow Transplant 46, 323–329 (2011). https://doi.org/10.1038/bmt.2010.260

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.260

Keywords

This article is cited by

Search

Quick links