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Alternative Donor Transplantation—“Mixing and Matching”: the Role of Combined Cord Blood and Haplo-Identical Donor Transplantation (Haplo-Cord SCT) as a Treatment Strategy for Patients Lacking Standard Donors?

  • Stem Cell Transplantation (R Maziarz, Section Editor)
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Abstract

In the past decade, haplo-cord stem cell transplantation (SCT) using myeloablative or reduced intensive conditioning regimens has been shown to result in reliable and fast engraftment of neutrophils and platelets comparable to HLA-matched donors and much faster than after cord stem cell transplant. Haplo-cord SCT also has a low incidence of early non-relapse mortality, low incidences of acute and chronic graft-vs-host disease (GVHD), and excellent graft-vs-leukemia (GVL) effects. Favorable long-term outcomes for high-risk patients with hematologic malignancies have been reported, including older patients. Haplo-cord SCT will likely overcome the limitations of cell dose during cord stem cell selection and might significantly expand the use of cord stem cell transplant in the adult population. The comparable survival outcomes of matched related donor (MRD), matched unrelated donor (MUD), and haplo-cord stem cell transplant strongly argue that haplo-cord SCT should be considered as effective alternative stem cell transplant for high-risk patients lacking standard donors. Further improvement in supportive care and incorporation of a better understanding of the human fetal immune development into the haplo-cord SCT are required to further improve this strategy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091–101.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP, et al. Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood. 2010;116(11):1839–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Schlenk RF, Dohner K, Mack S, Stoppel M, Kiraly F, Gotze K, et al. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol. 2010;28(30):4642–8.

    Article  PubMed  Google Scholar 

  4. Walter RB, Pagel JM, Gooley TA, Petersdorf EW, Sorror ML, Woolfrey AE. Comparison of matched unrelated and matched related donor myeloablative hematopoietic cell transplantation for adults with acute myeloid leukemia in first remission. Leukemia. 2010;24:1276–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. 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(4):339–48. Latest data on the likelihood to find a stem cell donor for different ethnicities from NMDP.

    Article  CAS  PubMed  Google Scholar 

  6. Ballen KK, Koreth J, Chen YB, Dey BR, Spitzer TR. Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant. Blood. 2011;119:1972–80.

    Article  PubMed  Google Scholar 

  7. Fuchs E, O’Donnell PV, Brunstein CG. Alternative transplant donor sources: is there any consensus? Curr Opin Oncol. 2013;25(2):173–9.

    Article  CAS  PubMed  Google Scholar 

  8. Fernandez Vina M, Heslop HE, Barker JN. New approaches in alternative donor transplantation. Biol Blood Marrow Transplant. 2013;19(1 Suppl):S91–6.

    Article  CAS  PubMed  Google Scholar 

  9. 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(6):641–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Symons HJ, Fuchs EJ. Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors. Bone Marrow Transplant. 2008;42(6):365–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood. 2010;116(22):4693–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. 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(22):2276–85.

    Article  CAS  PubMed  Google Scholar 

  13. Wagner JE, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014;371(18):1685–94. Prospective randomized study to demonstate comparable outcomes after double cord and signle cord transplant in pediatric patients with hematologic cancers.

    Article  CAS  PubMed  Google Scholar 

  14. Ruggeri A, Sanz G, Bittencourt H, Sanz J, Rambaldi A, Volt F, 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. 2013;28(4):779–86.

    Article  PubMed  Google Scholar 

  15. Sanz J, Wagner JE, Sanz MA, DeFor T, Montesinos P, Bachanova V, et al. Myeloablative cord blood transplantation in adults with acute leukemia: comparison of two different transplant platforms. Biol Blood Marrow Transplant. 2013;19(12):1725–30.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Bautista G, Cabrera JR, Regidor C, Fores R, Garcia-Marco JA, Ojeda E, et al. Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor. Bone Marrow Transplant. 2009;43(5):365–73.

    Article  CAS  PubMed  Google Scholar 

  17. Liu H, Rich ES, Godley L, Odenike O, Joseph L, Marino S, et al. Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. Blood. 2011;118(24):6438–45. First publication of RIC haplo-cord SCT in patients with hematologic malignancies.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Wang J, Zhan P, Ouyang J, Chen B, Zhou R, Yang Y. Unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients: a meta-analysis. Leuk Res. 2010;34(8):1018–22.

    Article  PubMed  Google Scholar 

  19. Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant. 2007;13(4):444–53.

    Article  PubMed  Google Scholar 

  20. Zhang H, Chen J, Que W. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in acute leukemia patients. Biol Blood Marrow Transplant. 2012;18(8):1164–73.

    Article  PubMed  Google Scholar 

  21. Brunstein CG. Umbilical cord blood transplantation for the treatment of hematologic malignancies. Cancer Control. 2011;18(4):222–36.

    PubMed  Google Scholar 

  22. Jacobson CA, Turki AT, McDonough SM, Stevenson KE, Kim HT, Kao G, et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2011;18(4):565–74.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Oran B, Wagner JE, DeFor TE, Weisdorf DJ, Brunstein CG. Effect of conditioning regimen intensity on acute myeloid leukemia outcomes after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2011;17(9):1327–34.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Majhail NS, Brunstein CG, Tomblyn M, Thomas AJ, Miller JS, Arora M, et al. Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor. Biol Blood Marrow Transplant. 2008;14(3):282–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Chen YB, Aldridge J, Kim HT, Ballen KK, Cutler C, Kao G, et al. Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts. Biol Blood Marrow Transplant. 2011;18(5):805–12.

    Article  PubMed  Google Scholar 

  26. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J. 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;118:282–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Solh M, Brunstein C, Morgan S, Weisdorf D. Platelet and red blood cell utilization and transfusion independence in umbilical cord blood and allogeneic peripheral blood hematopoietic cell transplants. Biol Blood Marrow Transplant. 2011;17(5):710–6.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Ramirez P, Brunstein CG, Miller B, Defor T, Weisdorf D. Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival. Bone Marrow Transplant. 2011;46(7):981–6.

    Article  CAS  PubMed  Google Scholar 

  29. Ballen KK, Spitzer TR. The great debate: haploidentical or cord blood transplant. Bone Marrow Transplant. 2011;46(3):323–9.

    Article  CAS  PubMed  Google Scholar 

  30. Gutman JA, Turtle CJ, Manley TJ, Heimfeld S, Bernstein ID, Riddell SR, et al. Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit. Blood. 2011;115(4):757–65.

    Article  Google Scholar 

  31. Dahlberg A, Delaney C, Bernstein ID. Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood. 2011;117(23):6083–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Norkin M, Lazarus HM, Wingard JR. Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic? Bone Marrow Transplant. 2013;48(7):884–9.

    Article  CAS  PubMed  Google Scholar 

  33. 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(6):535–44.

    Article  PubMed  Google Scholar 

  34. Kwon M, Bautista G, Balsalobre P, Sanchez-Ortega I, Serrano D, Anguita J, et al. Haplo-Cord Transplantation Using CD34 Cells from a Third-Party Donor to Speed Engraftment in High-Risk Patients with Hematologic Disorders. Biol Blood Marrow Transplant. 2014. The latest update of the outcomes of the largest so far cohort of 132 patients underwent myeloablative haplo-cord SCT in three Spanish institutions.

  35. Van Besien K, Liu H, Jain N, Stock W, Artz A. Umbilical cord blood transplantation supported by third-party donor cells: rationale, results, and applications. Biol Blood Marrow Transplant. 2013;19(5):682–91. Excellent review article on the halpo-cord SCT including deep discussion of the underlying fetal immune characteristics.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Taskinen MH, Huttunen P, Niittyvuopio R, Saarinen-Pihkala UM. Coinfusion of mobilized hematopoietic stem cells from an HLA-mismatched third-party donor with umbilical cord blood graft to support engraftment. J Pediatr Hematol Oncol. 2014;36(8):e518–23.

    Article  PubMed  Google Scholar 

  37. Kwon M, Martinez-Laperche C, Balsalobre P, Serrano D, Anguita J, Gayoso J, et al. Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells. Bone Marrow Transplant. 2014;49(2):212–8. Characteristics of chimerism dynamics after myeloablative haplo-cord SCT, and prediction of successful engraftment or graft failure using the early chimerism dynamics.

    Article  CAS  PubMed  Google Scholar 

  38. Newell LF, Milano F, Nicoud IB, Pereira S, Gooley TA, Heimfeld S, et al. Early CD3 peripheral blood chimerism predicts the long-term engrafting unit following myeloablative double-cord blood transplantation. Biol Blood Marrow Transplant. 2012;18(8):1243–9.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Cutler C, Kim HT, Sun L, Sese D, Glotzbecker B, Armand P, et al. Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood. 2011;118(25):6691–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Takanashi M, Atsuta Y, Fujiwara K, Kodo H, Kai S, Sato H, et al. The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood. 2010;116(15):2839–46.

    Article  CAS  PubMed  Google Scholar 

  41. Rocha V, Gluckman E. Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Br J Haematol. 2009;147(2):262–74.

    Article  CAS  PubMed  Google Scholar 

  42. Jain N, Liu H, Artz AS, Anastasi J, Odenike O, Godley LA, et al. Immune reconstitution after combined haploidentical and umbilical cord blood transplant. Leuk Lymphoma. 2013;54(6):1242–9.

    Article  CAS  PubMed  Google Scholar 

  43. Sebrango A, Vicuna I, de Laiglesia A, Millan I, Bautista G, Martin-Donaire T, et al. Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes. Best Pract Res Clin Haematol. 2010;23(2):259–74.

    Article  PubMed  Google Scholar 

  44. Kwon M, Balsalobre P, Serrano D, Pérez Corral A, BuÃ ± o I, Anguita J, et al. Single cord blood combined with HLA-mismatched third party donor cells: comparable results to matched unrelated donor transplantation in high-risk patients with hematologic disorders. Biol Blood Marrow Transplant. 2013;19(1):143–9. In this retrospective analysis with relatively small patient number, comparable clinical outcomes were found between haplo-cord SCT and MUD SCT in high risk patients with hematologic disorders.

    Article  PubMed  Google Scholar 

  45. Rhodes J, van Besien K, Liu H, Gergis U, Tsai SB, Mayer S, et al. Haplo-Cord Transplantation Vs Unrelated Donor Stem Cell Transplantation in Patients with AML/MDS Older Than 502,014 2014-12-06 00:00:00. 1235- p.

  46. Van Besien K, Artz AS, Zhang MJ, Cushing M, Wickrema A, Korman S, et al. Haplo + cord transplantation: Neutrophil and platelet recovery and long-term survival compared to double umbilical cord blood (UCB) transplantation—a case-cohort analysis. J Clin Oncol. 2014;32:(5S,):abstr 7004.

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Conflict of Interest

Dr. Hongtao Liu is supported by grant from Cancer Research Foundation and K12 Paul Calabresi award.

Dr. Koen van Besien has research support from Miltenyi Biotec.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Hongtao Liu

  2. Weill Cornell Medical College, New York, NY, USA

    Koen van Besien

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  1. Hongtao Liu
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  2. Koen van Besien
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Correspondence to Koen van Besien.

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Liu, H., van Besien, K. Alternative Donor Transplantation—“Mixing and Matching”: the Role of Combined Cord Blood and Haplo-Identical Donor Transplantation (Haplo-Cord SCT) as a Treatment Strategy for Patients Lacking Standard Donors?. Curr Hematol Malig Rep 10, 1–7 (2015). https://doi.org/10.1007/s11899-014-0245-y

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  • DOI: https://doi.org/10.1007/s11899-014-0245-y

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