Historical Perspective and Current Trends of Umbilical Cord Blood Transplantation

Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)


Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment for patients with hematological diseases. HLA-matched donors could be either siblings or unrelated donors found in international registries for unrelated donors. Patients in need of allo-HCT may also benefit of a HLA-mismatched allo-HCT either from a haploidentical donor or from umbilical cord blood (UCB). Much has been learned about UCBT since the first human cord blood transplant (UCBT) was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation, and distribution of UCB for allo-HCT. Today, a global network of cord blood banks and transplant centers has been established with a large common inventory of more than 650,000 UCB units available, allowing for more than 40,000 UCBT worldwide in children and adults with severe hematological diseases. Several studies have been published on UCBT, assessing risk factors such as cell dose and HLA mismatch. Outcomes of several retrospective comparative studies showed similar results using other graft sources both in pediatric and adult settings. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality.


Cord blood banking Cord blood transplantation Malignant and nonmalignant hematological diseases 


  1. Auerbach AD, Liu Q, Ghosh R, Pollack MS, Douglas GW, Broxmeyer HE (1990) Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia. Transfusion 30(8):682–687CrossRefPubMedGoogle Scholar
  2. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al (2005) Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 105(3):1343–1347CrossRefPubMedGoogle Scholar
  3. Barker JN, Scaradavou A, Stevens CE (2010) Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies. Blood 115(9):1843–1849CrossRefPubMedPubMedCentralGoogle Scholar
  4. Boitano AE, Wang J, Romeo R et al (2010) Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 329(5997):1345–1348CrossRefPubMedPubMedCentralGoogle Scholar
  5. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D et al (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A 86(10):3828–3832CrossRefPubMedPubMedCentralGoogle Scholar
  6. Broxmeyer HE, Hangoc G, Cooper S, Ribeiro RC, Graves V, Yoder M et al (1992) Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci U S A 89(9):4109–4113CrossRefPubMedPubMedCentralGoogle Scholar
  7. Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al (2007) Umbilical cord blood transplantation after non-myeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 110(8):3064–3070CrossRefPubMedPubMedCentralGoogle Scholar
  8. Brunstein CG, Gutman JA, Weisdorf DJ et al (2010) Allogeneic hematopoietic cell transplantation for hematologi malignancy: relative risks and benefits of double umbilical cord blood. Blood 116(22):4693–4699CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brunstein CG, Noreen H, DeFor TE, Maurer D, Miller JS, Wagner JE (2011) Anti-HLA antibodies in double umbilical cord blood transplantation. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl 17(11):1704–1708CrossRefGoogle Scholar
  10. Brunstein CG, Eapen M, Ahn KW et al (2012) Reduced intensity conditioning in acute leukemia: the effect of source of unrelated donor stem cells on outcome. Blood 119(23):5591–5598CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brunstein CG1, McKenna DH, DeFor TE, Sumstad D, Paul P, Weisdorf DJ, et al (2013)Complement fragment 3a priming of umbilical cord blood progenitors: safety profile. Biol Blood Marrow Transplant. 2013;19(10):1474–1479Google Scholar
  12. Cairo MS, Wagner JE (1997) Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation. Blood 90(12):4665–4678PubMedGoogle Scholar
  13. Cuttler C, Kim HT, Sun L, Sese D, Glotzbecker B, Armand P et al (2011) Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood 118(25):6691–6697CrossRefGoogle Scholar
  14. Cuttler C, Multani P, Robbins D et al (2013) Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 122(17):3074–3081CrossRefGoogle Scholar
  15. Dahi PB, Barone J, Devlin SM, Byam C, Lubin M, Ponce DM, Giralt S, Kernan NA, Scaradavou A, Hsu SH, Barker JN (2014) Sustained donor engraftment in recipients of double-unit cord blood transplantation is possible despite donor-specific human leukocyte antigen antibodies. Biol Blood Marrow Transplant 20(5):735–739CrossRefPubMedPubMedCentralGoogle Scholar
  16. de Lima M, McMannis J, Gee A et al (2008) Transplantation of ex vivo expanded cord blood cells using the copper chelator tetra ethyelenepentamine: a phase I/II clinical trial. Bone Marrow Transplant 41(9):771–778Google Scholar
  17. de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M, Alousi A, Saliba R, McMannis JD, Kaur I, Kebriaei P, Parmar S, Popat U, Hosing C, Champlin R, Bollard C, Molldrem JJ, Jones RB, Nieto Y, Andersson BS, Shah N, Oran B, Cooper LJ, Worth L, Qazilbash MH, Korbling M, Rondon G, Ciurea S, Bosque D, Maewal I, Simmons PJ, Shpall EJ (2012) Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med 367(24):2305–2315CrossRefPubMedPubMedCentralGoogle Scholar
  18. Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID (2010) Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 16(2):232–236CrossRefPubMedPubMedCentralGoogle Scholar
  19. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al (2007) Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 369(9577):1947–1954CrossRefPubMedGoogle Scholar
  20. Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W et al (2010) Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol 11(7):653–660CrossRefPubMedPubMedCentralGoogle Scholar
  21. Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C et al (2011) 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 12(13):1214–1221CrossRefPubMedPubMedCentralGoogle Scholar
  22. Eapen M, Klein JP, Ruggeri A, Spellman S, Lee SJ, Anasetti C, Arcese W, Barker JN, Baxter-Lowe LA, Brown M, Fernandez-Vina MA, Freeman J, He W, Iori AP, Horowitz MM, Locatelli F, Marino S, Maiers M, Michel G, Sanz GF, Gluckman E, Rocha V (2014) Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood 123(1):133–140CrossRefPubMedPubMedCentralGoogle Scholar
  23. Farag SS, Srivastava S, Messina-Graham S, Schwartz J, Robertson MJ, Abonour R, Cornetta K, Wood L, Secrest A, Strother RM, Jones DR, Broxmeyer HE (2013) In vivo DPP-4 inhibition to enhance engraftment of single-unit cord blood transplants in adults with hematological malignancies. Stem Cells Dev 22(7):1007–1015CrossRefPubMedGoogle Scholar
  24. Gluckman E, Devergie A, Dutreix J (1983) Radiosensitivity in Fanconi anaemia: application to the conditioning regimen for bone marrow transplantation. Br J Haematol 54(3):431–440CrossRefPubMedGoogle Scholar
  25. Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A et al (1989) Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 321(17):1174–1178CrossRefPubMedGoogle Scholar
  26. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R et al (1997) 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 337(6):373–381CrossRefPubMedGoogle Scholar
  27. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al (2004) Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 32(4):397–407CrossRefPubMedGoogle Scholar
  28. Horwitz ME, Chao NJ, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris A, McDonald C, Waters-Pick B, Stiff P, Wease S, Peled A, Snyder D, Cohen EG, Shoham H, Landau E, Friend E, Peleg I, Aschengrau D, Yackoubov D, Kurtzberg J, Peled T (2014) Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest 124(7):3121–3128CrossRefPubMedPubMedCentralGoogle Scholar
  29. Jaroscak J, Goltry K, Smith A et al (2003) Augmentation of umbilical cord blood (UCB) transplantation with ex-vivo expanded UCB cells: results of a phase 1 trial using the AastromReplicel System. Blood 101(12):5061–5067CrossRefPubMedGoogle Scholar
  30. Komanduri KV, St John LS, de Lima M, McMannis J, Rosinski S, McNiece I et al (2007) Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing. Blood 110(13):4543–4551CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC et al (1996) Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 335(3):157–166CrossRefPubMedGoogle Scholar
  32. Kurtzberg J, Prasad VK, Carter SL, Wagner JE, Baxter-Lowe LA, Wall D, Kapoor N, Guinan EC, Feig SA, Wagner EL, Kernan NA, COBLT Steering Committee (2008) Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 112(10):4318–4327CrossRefPubMedPubMedCentralGoogle Scholar
  33. Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE et al (2001) Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 344(24):1815–1822CrossRefPubMedGoogle Scholar
  34. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al (2004) Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 351(22):2265–2275CrossRefPubMedGoogle Scholar
  35. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al (1999) Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 93(11):3662–3671PubMedGoogle Scholar
  36. MacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR et al (2009) Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 113(11):2410–2415CrossRefPubMedPubMedCentralGoogle Scholar
  37. Malard F, Milpied N, Blaise D et al (2015) Effect of graft source on unrelated donor hematopoietic stem cell transplantation in adults with acute myeloid leukemia after reduced–intensity or non myeloablative conditioning: a study from the Société Francaise de Greffe de Moelle et de thérapie cellulaire. Biol Blood Marrow Transplant 21(6):1059–1067Google Scholar
  38. Michel G, Galambrun C, Sirvent A, Pochon C, Bruno B, Jubert C, Loundou A, Yakoub-Agha I, Milpied N, Lutz P, Marie-Cardine A, Gandemer V, Blaise D, Michallet M, Rialland F, Renard C, Oudin C, Esmiol S, Seux M, Baumstarck K, Mohty M, Rocha V, Dalle JH (2016) Single versus double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome. Blood 127:3450–3457. Pii: blood-2016-01-694349. [Epub ahead of print]Google Scholar
  39. Robinson SN, Thomas MW, Simmons PJ et al (2014) Fucolysation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment. Cytotherapy 16(1):84–89Google Scholar
  40. Rocha V, Wagner JE Jr, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM et al (2000) 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 342(25):1846–1854Google Scholar
  41. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al (2004) Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 351(22):2276–2285CrossRefPubMedGoogle Scholar
  42. Rubinstein P, Rosenfield RE, Adamson JW, Stevens CE (1993) Stored placental blood for unrelated bone marrow reconstitution. Blood 81(7):1679–1690PubMedGoogle Scholar
  43. Rubinstein P, Dobrila L, Rosenfield RE, Adamson JW, Migliaccio G, Migliaccio AR et al (1995) Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci U S A 92(22):10119–10122CrossRefPubMedPubMedCentralGoogle Scholar
  44. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al (1998) Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 339(22):1565–1577CrossRefPubMedGoogle Scholar
  45. Ruggeri A, Peffault de Latour R, Carmagnat M, Clave E, Douay C, Larghero J et al (2011) Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases. Transpl Infect Dis 13(5):456–465CrossRefPubMedGoogle Scholar
  46. Ruggeri A, Rocha V, Masson E, Labopin M, Cunha R, Absi L, Boudifa A, Coeffic B, Devys A, De Matteis M, Dubois V, Hanau D, Hau F, Jollet I, Masson D, Pedron B, Perrier P, Picard C, Ramouneau-Pigot A, Volt F, Charron D, Gluckman E, Loiseau P (2013) Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, SFHI and SFGM-TC analysis. Haematologica 98(7):1154–1160CrossRefPubMedPubMedCentralGoogle Scholar
  47. Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, Blaise D, Bosi A, Huang H, Karakasis D, Koc Y, Michallet M, Picardi A, Sanz J, Santarone S, Sengelov H, Sierra J, Vincent L, Volt F, Nagler A, Gluckman E, Ciceri F, Rocha V, Mohty M (2015) Comparison of outcomes after unrelated cord blood and unmanipulated Haploidentical stem cell transplantation in adults with acute leukemia. Leukemia 29(9):1891–1900CrossRefPubMedGoogle Scholar
  48. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragan E et al (2001) Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 98(8):2332–2338CrossRefPubMedGoogle Scholar
  49. Scaradavou A, Brunstein CG, Eapen M, Le-Rademacher J, Barker JN, Chao N, Cuttler C, Delaney C, Kan F, Isola L, Karanes C, Laughlin MJ, Wagner JE, Shpall EJ (2013) Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood 121(5):752–758CrossRefPubMedPubMedCentralGoogle Scholar
  50. Shpall EJ, Quinones R, Giller R et al (2002) Biol Blood Marrow Transplant 8(7):368–376CrossRefPubMedGoogle Scholar
  51. Takanashi M, Atsuta Y, Fujiwara K, Kodo H, Kai S, Sato H et al (2010) The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood 116(15):2839–2846CrossRefPubMedGoogle Scholar
  52. Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH et al (2009) Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 114(19):4293–4299CrossRefPubMedPubMedCentralGoogle Scholar
  53. Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK et al (1996) Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood 88(3):795–802PubMedGoogle Scholar
  54. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al (2002) 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 100(5):1611–1618PubMedGoogle Scholar
  55. Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, Walters M, Horowitz MM, Kurtzberg J, Blood and Marrow Transplant Clinical Trials Network (2014) One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 371(18):1685–1694CrossRefPubMedPubMedCentralGoogle Scholar
  56. Xia D, He HY, Lei ZM et al (2004) Surface fucolysation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow. Blood 104(10):3091–3096CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Eurocord, Hopital Saint LouisParis Cedex 10France
  2. 2.Monacord, Centre scientifique de MonacoMonacoFrance
  3. 3.Service d’Hématologie et Thérapie CellulaireHôpital Saint-AntoineParisFrance

Personalised recommendations