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Adult umbilical cord blood transplantation: a comprehensive review

Abstract

Recent registry studies have established umbilical cord blood (UCB) transplantation as a safe and feasible alternative to bone marrow transplantion in adults when no sibling donor is available. There is, however, no gold standard to guide optimal treatment choices. We review here factors leading to the choice of the ‘best available donor’ and ‘best available unit’ in the case of UCB. For instance, it is clear that higher cell dose may partially overcome the negative impact of certain histocompatibility leukocyte antigen (HLA) disparities in UCB transplantation, leading us to choose the more closely HLA-matched unit with a cell dose >2.5 × 107/kg. New approaches in adult UCB transplantation are systematically covered, with a quantitative appreciation of the evidence available to date. Reduced intensity conditioning, for example, broadens the range of potential recipients by reducing transplant-related mortality, but suffers from unproven risks and benefits long term. Potential advantages of multiple units over single unit transplants are discussed, with a particular emphasis on confounding factors that impact interpretation. The limited clinical results of ex vivo UCB expansion, the possible benefits of co-infusion of haploidentical cells and controversial issues (e.g. killer immunoglobulin-like receptor matching and alternative graft sources) are also addressed with a debate on the future of UCB transplantation.

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References

  1. Migliaccio AR, Adamson JW, Stevens CE, Dobrila NL, Carrier CM, Rubinstein P . 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: 2717–2722.

    CAS  PubMed  Google Scholar 

  2. 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 

  3. 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 

  4. Barker J, Scaradavou A, Stevens CE, Rubinstein P . Analysis of 608 umbilical cord blood (UCB) transplants: hla-match is a critical determinant of transplant-related mortality (TRM) in the post-engraftment period even in the absence of acute graft-vs-host disease (aGVHD). Blood 2005; 106: 92a–93a (Abstract 303).

    Google Scholar 

  5. Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ . Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant 2002; 8: 257–260.

    Article  PubMed  Google Scholar 

  6. Hamza NS, Lisgaris M, Yadavalli G, Nadeau L, Fox R, Fu P et al. Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults. Br J Haematol 2004; 124: 488–498.

    Article  PubMed  Google Scholar 

  7. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.

    Article  CAS  PubMed  Google Scholar 

  8. Gluckman E, Koegler G, Rocha V . Human leukocyte antigen matching in cord blood transplantation. Semin Hematol 2005; 42: 85–90.

    Article  CAS  PubMed  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. Kogler G, Enczmann J, Rocha V, Gluckman E, Wernet P . High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome. Bone Marrow Transplant 2005; 36: 1033–1041.

    Article  CAS  PubMed  Google Scholar 

  11. Stevens C, Scaradavou A, Carrier C, Carpenter C, Rubinstein P . An empirical analysis of the probability of finding a well matched cord blood unit: implications for a national cord blood inventory. Blood 2005; 106: 579a (Abstract 2047).

    Google Scholar 

  12. Bradley MB, Cairo MS . Cord blood immunology and stem cell transplantation. Hum Immunol 2005; 66: 431–446.

    Article  CAS  PubMed  Google Scholar 

  13. Bignon J-D, Gagne K . KIR matching in hematopoietic stem cell transplantation. Curr Opin Immunol 2005; 17: 553–559.

    Article  CAS  PubMed  Google Scholar 

  14. Brunstein CG, Wagner JE, Weisdorf DJ, Barker JN, Noreen H, Tan Y et al. Negative impact of KIR-ligand mismatch on transplant-related mortality (TRM) in umbilical cord blood transplant (UCBT) recipients. ASH Annual Meeting Abstracts 2005; 106: 577a–578a (Abstract 2041).

    Google Scholar 

  15. 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  PubMed  Google Scholar 

  16. 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 

  17. 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  PubMed  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  PubMed  Google Scholar 

  19. Long GD, Laughlin M, Madan B, Kurtzberg J, Gasparetto C, Morris A et al. Unrelated umbilical cord blood transplantation in adult patients. Biol Blood Marrow Transplant 2003; 9: 772–780.

    Article  PubMed  Google Scholar 

  20. Sanz GF, Saavedra S, Jimenez C, Senent L, Cervera J, Planelles D et al. Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution. Bone Marrow Transplant 2001; 27: 693–701.

    Article  CAS  PubMed  Google Scholar 

  21. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragan E et al. Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 2001; 98: 2332–2338.

    Article  CAS  PubMed  Google Scholar 

  22. Saavedra S, Sanz GF, Jarque I, Moscardo F, Jimenez C, Lorenzo I et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplant 2002; 30: 937–943.

    Article  CAS  PubMed  Google Scholar 

  23. Ooi J, Iseki T, Takahashi S, Tomonari A, Tojo A, Asano S . Unrelated cord blood transplantation for adult patients with acute lymphoblastic leukemia. Leukemia 2004; 18: 1905–1907.

    Article  CAS  PubMed  Google Scholar 

  24. Ooi J, Iseki T, Takahashi S, Tomonari A, Takasugi K, Uchiyama M et al. Unrelated cord blood transplantation after myeloablative conditioning in patients over the age of 45 years. Br J Haematol 2004; 126: 711–714.

    Article  PubMed  Google Scholar 

  25. Ooi J, Iseki T, Takahashi S, Tomonari A, Takasugi K, Shimohakamada Y et al. Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia. Blood 2004; 103: 489–491.

    Article  CAS  PubMed  Google Scholar 

  26. Ooi J, Iseki T, Takahashi S, Tomonari A, Ishii K, Takasugi K et al. Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. Blood 2003; 101: 4711–4713.

    Article  CAS  PubMed  Google Scholar 

  27. Ooi J, Iseki T, Takahashi S, Tomonari A, Nagayama H, Ishii K et al. A clinical comparison of unrelated cord blood transplantation and unrelated bone marrow transplantation for adult patients with acute leukaemia in complete remission. Br J Haematol 2002; 118: 140–143.

    Article  PubMed  Google Scholar 

  28. Ooi J, Iseki T, Nagayama H, Tomonari A, Ito K, Shirafuji N et al. Unrelated cord blood transplantation for adult patients with myelodysplastic syndrome-related secondary acute myeloid leukaemia. Br J Haematol 2001; 114: 834–836.

    Article  CAS  PubMed  Google Scholar 

  29. Sanz MA . Cord-blood transplantation in patients with leukemia – a real alternative for adults. N Engl J Med 2004; 351: 2328–2330.

    Article  CAS  PubMed  Google Scholar 

  30. Cornetta K, Laughlin M, Carter S, Wall D, Weinthal J, Delaney C et al. Umbilical cord blood transplantation in adults: results of the prospective Cord Blood Transplantation (COBLT). Biol Blood Marrow Transplant 2005; 11: 149–160.

    Article  PubMed  Google Scholar 

  31. Broxmeyer HE, Christopherson Ii KW, Hangoc G, Campbell TB . Augmentation of homing of cord blood stem cells. Biol Blood Marrow Transplant 2005; 11: 933.

    Article  Google Scholar 

  32. Chan S, Choi M, Wnendt S, Kraus M, Teng E, Leong H et al. Enhanced in vivo homing of uncultured and selectively amplified umbilical cord blood CD34+ cells by co-transplantation with cord blood derived unrestricted somatic stem cells. Blood 2005; 106: 371a–372a (Abstract 1276).

    Google Scholar 

  33. Laughlin M . In vivo stem cell factor (R-MetHuSCF) and filgrastim administration after unrelated UCB transplantation in adults. Biol Blood Marrow Transplant 2005; 11: 932.

    Article  Google Scholar 

  34. Brunstein CG, Barker JN, DeFor TE, French K, Weisdorf DJ, Wagner JE . Non-myeloablative (NMA) umbilical cord blood transplantation (UCBT): promising disease-free survival in 95 consecutive patients. ASH Annual Meeting Abstracts 2005; 106: 166a (Abstract 559).

    Google Scholar 

  35. Tashiro H, Kozai Y, Goto M, Noguchi M, Shirasaki R, Kawasugi K et al. Comparison of adult allogeneic umbilical cord blood transplantation between myeloablative and non-myeloablative conditioning regimens. Biol Blood Marrow Transplant 2005; 11: 929 (Abstract 5).

    Article  Google Scholar 

  36. Chao NJ, Koh LP, Long GD, Gasparetto C, Horwitz M, Morris A et al. Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens. Biol Blood Marrow Transplant 2004; 10: 569–575.

    Article  PubMed  Google Scholar 

  37. Rio B, Belhocine R, Renaud M, Francois S, Gluckman E, Blaise D et al. Reduced intensity conditioning regimen for unrelated cord blood transplantation in adults. A multicentric phase I–II trial. ASH Annual Meeting Abstracts 2005; 106: 1018a (Abstract 3658).

    Google Scholar 

  38. Miyakoshi S, Yuji K, Kusumi E, Kato D, Koyama S, Fujiwara M et al. Reduced-intensity unrelated cord blood transplantation (RICBT) for adults with hematological diseases. ASH Annual Meeting Abstracts 2004; 104: 756a–757a (Abstract 2763).

    Google Scholar 

  39. Hamaki T, Kajiwara K, Hoshi K, Kogure K, Harima A, Yamada K et al. Reduced intensity cord blood transplantation using mycophenolate mofetil and cyclosporine for adult patients with advanced hematologic malignancies. ASH Annual Meeting Abstracts 2005; 106: 809a–810a (Abstract 2889).

    Google Scholar 

  40. Ballen KK, Spitzer TR, Yeap B, Steve M, Dey BR, Attar E et al. Excellent disease-free survival after double cord blood transplantation using a reduced intensity chemotherapy only conditioning regimen in a diverse adult population. ASH Annual Meeting Abstracts 2005; 106: 579a–580a (Abstract 2048).

    Google Scholar 

  41. 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  PubMed  Google Scholar 

  42. Barker J, Weisdorf D, DeFor T, Brunstein C, Wagner J . umbilical cord blood (UCB) transplantation after non-myeloablative (NMA) conditioning for advanced follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia: low transplant-related mortality and high progression-free survival. Blood 2005; 106: 813a (Abstract 2900).

    Google Scholar 

  43. Brunstein C, Barker J, DeFor T, French K, Weisdorf D, Wagner J . Non-myeloablative (NMA) umbilical cord blood transplantation (UCBT): promising disease-free survival in 95 consecutive patients. Blood 2005; 106: 166a (Abtract 559).

    Google Scholar 

  44. 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 

  45. Kai S, Misawa M, Iseki T, Takahashi S, Kishi K, Hiraoka A et al. Double-unit cord blood transplantation in Japan. ASH Annual Meeting Abstracts 2004; 104: 3765 (Abstract 5166).

    Google Scholar 

  46. 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. ASH Annual Meeting Abstracts 2005; 106: 93a (Abstract 305).

    Google Scholar 

  47. Rubinstein P, Stevens CE, Scaradavou A . Cord blood transplantation to adult patients: a New York blood center update. Biol Blood Marrow Transplant 2005; 11: 928 (Abstract 928).

    Article  Google Scholar 

  48. Creer MH, Regan D, Alonso M, Wooford J . Myeloablative single cord transplants (SCT) versus dual cord transplants (DCT) in adults with acute leukemia. ASH Annual Meeting Abstracts 2005; 106: 3866 (Abstract 5209).

    Google Scholar 

  49. Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB et al. Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant 2002; 8: 368–376.

    Article  PubMed  Google Scholar 

  50. Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin PL, Driscoll TA et al. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood 2003; 101: 5061–5067.

    Article  CAS  PubMed  Google Scholar 

  51. Devine SM, Lazarus HM, Emerson SG . Clinical application of hematopoietic progenitor cell expansion: current status and future prospects. Bone Marrow Transplant 2003; 31: 241–252.

    Article  CAS  PubMed  Google Scholar 

  52. 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  PubMed  Google Scholar 

  53. Fernandez MN . Unrelated single cord blood transplants supported by co-infusion of a low number of mobilized peripheral blood highly purified CD34+ cells from a third party donor after low toxicity myeloablative conditioning. Biol Blood Marrow Transplant 2005; 11: 930 (Abstract 8).

    Article  Google Scholar 

  54. Majhail NS, Weisdorf DJ, Wagner JE, Defor TE, Brunstein CG, Burns LJ . Comparable results of umbilical cord blood and HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity preparative regimen for advanced Hodgkin lymphoma. Blood 2006; 107: 3804–3807.

    Article  CAS  PubMed  Google Scholar 

  55. Kumar P, Defor TE, Brunstein C, Barker J, Wagner JE, Weisdorf DJ et al. Allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of acute lymphocytic leukemia (ALL) in 126 adults: impact of donor source on leukemia free survival (LFS). ASH Annual Meeting Abstracts 2005; 106: 584a (Abstract, 2064).

    Google Scholar 

  56. Rocha V, Gluckman E . Clinical use of umbilical cord blood hematopoietic stem cells. Biol Blood Marrow Transplant 2006; 12 (Suppl 1): 34–41.

    Article  PubMed  Google Scholar 

  57. Grewal SS, Barker JN, Davies SM, Wagner JE . Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood 2003; 101: 4233–4244.

    Article  CAS  PubMed  Google Scholar 

  58. Europdonor. Bone Marrow Donors Worldwide, annual report, 2005.

  59. Kennedy GA, Morton J, Western R, Butler J, Daly J, Durrant S . Impact of stem cell donation modality on normal donor quality of life: a prospective randomized study. Bone Marrow Transplant 2003; 31: 1033–1035.

    Article  CAS  PubMed  Google Scholar 

  60. Switzer GE, Goycoolea JM, Dew MA, Graeff EC, Hegland J . Donating stimulated peripheral blood stem cells vs bone marrow: do donors experience the procedures differently? Bone Marrow Transplant 2001; 27: 917–923.

    Article  CAS  PubMed  Google Scholar 

  61. Karlsson L, Quinlan D, Guo D, Brown C, Selinger S, Klassen J et al. Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue. Bone Marrow Transplant 2004; 33: 709–713.

    Article  CAS  PubMed  Google Scholar 

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Schoemans, H., Theunissen, K., Maertens, J. et al. Adult umbilical cord blood transplantation: a comprehensive review. Bone Marrow Transplant 38, 83–93 (2006). https://doi.org/10.1038/sj.bmt.1705403

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