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Selection of an umbilical cord blood graft for hematopoietic cell transplantation

Nelson J Chao, MD
Section Editor
Robert S Negrin, MD
Deputy Editor
Alan G Rosmarin, MD


Allogeneic hematopoietic cell transplantation (HCT) is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant diseases. The pluripotent hematopoietic stem cells required for this procedure are usually obtained from the bone marrow or peripheral blood of a related or unrelated donor. Umbilical cord blood (UCB), the blood remaining in the umbilical cord and placenta following the birth of an infant, has emerged as an established alternative source of hematopoietic stem cells in allogeneic HCT.

Engraftment and survival rates following HCT are optimized when the donor and recipient are genetically compatible. Human leukocyte antigen (HLA)-matched sibling donors are generally the preferred donor source for an allogeneic HCT. Unfortunately, finding an HLA-matched sibling is not always possible. Each full sibling potential donor has only a 25 percent chance of being fully HLA-matched with a sibling requiring a transplant. Therefore, most patients do not have an HLA-identical relative. (See "Donor selection for hematopoietic cell transplantation", section on 'Matched sibling donors'.)

When a suitable related donor is not available, a search is conducted to identify a potential unrelated HLA-matched donor. Finding an appropriate donor through a national registry is a lengthy process that is not always successful, especially for individuals who are not of Northern European descent. Haploidentical donors have also emerged as an alternative source. (See "Donor selection for hematopoietic cell transplantation", section on 'Unrelated donors' and "HLA-haploidentical hematopoietic cell transplantation".)

In comparison, the relative ease of procurement and the lower than anticipated risk of severe acute graft-versus-host disease has made unrelated UCB transplantation a possible alternative to unrelated donor bone marrow or mobilized peripheral blood progenitor cell transplant. The increased representation of ethnic minorities and the ability to use partially HLA-matched UCB units significantly expands the donor pool. In addition, the use of reduced-intensity or non-myeloablative preparative regimens to allow engraftment of UCB broadens the scope of patients who may benefit from allogeneic HCT, including elderly and medically infirm patients without an HLA-matched sibling donor.

The advantages and limitations of UCB and the selection of an umbilical cord blood graft are discussed here. Other issues related to UCB are discussed separately, including the use of UCB transplantation in adults using myeloablative and non-myeloablative preparative regimens, and the collection, storage, and ethical issues regarding the use of UCB for HCT. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation" and "Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens" and "Sources of hematopoietic stem cells" and "Donor selection for hematopoietic cell transplantation".)


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Literature review current through: Sep 2016. | This topic last updated: Aug 16, 2016.
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  1. Gluckman E, Broxmeyer HA, Auerbach AD, 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.
  2. Navarrete C, Contreras M. Cord blood banking: a historical perspective. Br J Haematol 2009; 147:236.
  3. http://www.bmdw.org/ (Accessed on July 13, 2011).
  4. Querol S, Rubinstein P, Marsh SG, et al. Cord blood banking: 'providing cord blood banking for a nation'. Br J Haematol 2009; 147:227.
  5. Howe CW, Radde-Stepaniak T. Hematopoietic cell donor registries. In: Hematopoietic Cell Transplantation, 2nd ed, Thomas ED, Blume KG, Forman SJ (Eds), Blackwell Science, Malden 1999. p.503.
  6. Barker JN, Wagner JE. Umbilical cord blood transplantation: current state of the art. Curr Opin Oncol 2002; 14:160.
  7. Kernan NA, Bartsch G, Ash RC, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 1993; 328:593.
  8. Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313:765.
  9. Gluckman E, Rocha V, Chevret S. Results of unrelated umbilical cord blood hematopoietic stem cell transplant. Transfus Clin Biol 2001; 8:146.
  10. Barker JN, Krepski TP, DeFor TE, et al. Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002; 8:257.
  11. Rocha V, Wagner JE Jr, Sobocinski KA, 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.
  12. Gluckman E, Rocha V, Boyer-Chammard A, 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.
  13. Rubinstein P, Carrier C, Scaradavou A, et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339:1565.
  14. Delaney C, Gutman JA, Appelbaum FR. Cord blood transplantation for haematological malignancies: conditioning regimens, double cord transplant and infectious complications. Br J Haematol 2009; 147:207.
  15. Smith AR, Wagner JE. Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood. Br J Haematol 2009; 147:246.
  16. Daikeler T, Labopin M, Ruggeri A, et al. New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation. Blood 2013; 121:1059.
  17. Popat U, Mehta RS, Rezvani K, et al. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood 2015; 125:2885.
  18. Horwitz ME, Chao NJ, Rizzieri DA, et al. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest 2014; 124:3121.
  19. Barker JN, Byam C, Scaradavou A. How I treat: the selection and acquisition of unrelated cord blood grafts. Blood 2011; 117:2332.
  20. Stotler C, Bolwell B, Sobecks R, et al. Are backup BM harvests worthwhile in unrelated donor allogeneic transplants? Bone Marrow Transplant 2010; 45:49.
  21. Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007; 110:4576.
  22. 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.
  23. Eapen M, Klein JP, Sanz GF, 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.
  24. Eapen M, Rubinstein P, Zhang MJ, 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.
  25. Eapen M, Rocha V, Sanz G, et al. Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol 2010; 11:653.
  26. Stevens CE, Carrier C, Carpenter C, et al. HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection. Blood 2011; 118:3969.
  27. Cutler C, Kim HT, Sun L, et al. Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood 2011; 118:6691.
  28. Ruggeri A, Rocha V, Masson E, et al. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis. Haematologica 2013; 98:1154.
  29. Rocha V, Gluckman E, Eurocord-Netcord registry and European Blood and Marrow Transplant group. Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Br J Haematol 2009; 147:262.
  30. Eapen M, Klein JP, Ruggeri A, 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.
  31. Avery S, Shi W, Lubin M, et al. Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts. Blood 2011; 117:3277.
  32. Sekine T, Marin D, Cao K, et al. Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation. Blood 2016; 128:297.
  33. McCullough J, McKenna D, Kadidlo D, et al. Mislabeled units of umbilical cord blood detected by a quality assurance program at the transplantation center. Blood 2009; 114:1684.
  34. Wagner JE, Barker JN, DeFor TE, 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.
  35. Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97:2962.
  36. Gluckman E, Rocha V, Arcese W, et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32:397.
  37. Barker JN, Weisdorf DJ, DeFor TE, et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105:1343.
  38. Brunstein CG, Barker JN, Weisdorf DJ, et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110:3064.
  39. Ballen KK, Spitzer TR, Yeap BY, et al. Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transplant 2007; 13:82.
  40. Chen YB, Spitzer TR. Current status of reduced-intensity allogeneic stem cell transplantation using alternative donors. Leukemia 2008; 22:31.
  41. Scaradavou A, Brunstein CG, Eapen M, et al. Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood 2013; 121:752.
  42. Ruggeri A, Sanz G, Bittencourt H, et al. Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the Acute Leukemia Working Party of EBMT. Leukemia 2014; 28:779.
  43. Verneris MR, Brunstein CG, Barker J, et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009; 114:4293.
  44. Wagner JE Jr, Eapen M, Carter S, et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 2014; 371:1685.
  45. Sideri A, Neokleous N, Brunet De La Grange P, et al. An overview of the progress on double umbilical cord blood transplantation. Haematologica 2011; 96:1213.
  46. Berglund S, Okas M, Gertow J, et al. Stable mixed donor-donor chimerism after double cord blood transplantation. Int J Hematol 2009; 90:526.
  47. Michel G, Galambrun C, Sirvent A, et al. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome. Blood 2016; 127:3450.
  48. Migliaccio AR, Adamson JW, Stevens CE, et al. Cell dose and speed of engraftment in placental/umbilical cord blood transplantation: graft progenitor cell content is a better predictor than nucleated cell quantity. Blood 2000; 96:2717.
  49. Yoo KH, Lee SH, Kim HJ, et al. The impact of post-thaw colony-forming units-granulocyte/macrophage on engraftment following unrelated cord blood transplantation in pediatric recipients. Bone Marrow Transplant 2007; 39:515.
  50. Alonso JM 3rd, Regan DM, Johnson CE, et al. A simple and reliable procedure for cord blood banking, processing, and freezing: St Louis and Ohio Cord Blood Bank experiences. Cytotherapy 2001; 3:429.
  51. Scaradavou A, Smith KM, Hawke R, et al. Cord blood units with low CD34+ cell viability have a low probability of engraftment after double unit transplantation. Biol Blood Marrow Transplant 2010; 16:500.
  52. Fernández MN. Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors. Br J Haematol 2009; 147:161.
  53. Liu H, Rich ES, Godley L, et al. Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. Blood 2011; 118:6438.
  54. de Lima M, McNiece I, Robinson SN, et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med 2012; 367:2305.
  55. Brunstein CG, Gutman JA, Weisdorf DJ, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116:4693.
  56. Rosenau EH, Sugrue MW, Haller M, et al. Characteristics of thawed autologous umbilical cord blood. Transfusion 2012; 52:2234.