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.

  • Original Article
  • Published:

Cord Blood Stem Cells

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Bone Marrow Transplantation volume 49, pages 206–211 (2014)Cite this article

Subjects

Abstract

We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11–20 days), and for platelets was 15 days (11–180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II–IV acute GVHD was 20%±0.327% at day+100, and the incidence of chronic GVHD was 19.26%±1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk=5.012, 95% confidence interval, 1.146–21.927, P=0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Weisdorf DJ, Nelson G, Lee SJ, Haagenson M, Spellman S, Antin JH et al. Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: refined HLA matching reveals more graft-versus-host disease but not less relapse. Biol Blood Marrow Transplant 2009; 15: 1475–1478.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gupta V, Tallman MS, He w, Logan BR, Copelan E, Gale RP et al. Comparable survival after HLA-well-matche d unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood 2010; 116: 1839–1848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dew A, Collins D, Artz A, Rich E, Stock W, Swanson K et al. Paucity of HLA-identical unrelated donors for African-Americans with hematologic malignancies: the need for new donor options. Biol Blood Marrow Transplant 2008; 14: 938–941.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Godley LA, van Besien K . The next frontier for stem cell transplantation: finding a donor for all. J Am Med Assoc 2010; 303: 1421–1422.

    Article  CAS  Google Scholar 

  5. Zuckerman T, Rowe JM . Alternative donor transplantation in acute myeloid leukemia: which source and when? Curr Opin Hematal 2007; 14: 152–161.

    Article  Google Scholar 

  6. Joshua TV, Rizzo JD, Zhang MJ, Hari PN, Kurian S, Pasquini M et al. Access to hematopoietic stem cell transplantation: effect of race and sex. Cancer 2010; 116: 3469–3476.

    Article  PubMed  Google Scholar 

  7. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  8. Filiovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  Google Scholar 

  9. Huang X . HLA-mismatched/haploidentical hematopoietic stem cell transplantation: a field in which Chinese doctors are making great contributions. Chin Med J 2010; 10: 1235–1240.

    Google Scholar 

  10. 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: 4693–4699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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: 6438–6445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ballen KK, Spitzer TR . The great debate: haploidentical or cord blood transplant. Bone Marrow Transplant 2010; 46: 323–329.

    Article  PubMed  Google Scholar 

  13. Majhail NS, Mothukuri JM, Brunstein CG, Weisdorf DJ . Costs of hematopoietic cell transplantation: comparison of umbilical cord blood and matched related donor transplantation and the impact of posttransplant complications. Biol Blood marrow Transplant 2009; 15: 564–573.

    Article  PubMed  Google Scholar 

  14. 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: 981–986.

    Article  CAS  PubMed  Google Scholar 

  15. 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: 710–716.

    Article  PubMed  Google Scholar 

  16. Brunstein CG, Setubal DC, Wagner JE . Expanding the role of umbilical cord blood transplantation. Br J Haematol 2007; 137: 20–35.

    Article  PubMed  Google Scholar 

  17. Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E et al. Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Bilo Blood Marrow Transplant 2007; 13: 82–89.

    Article  CAS  Google Scholar 

  18. Frassoni F, Varaldo R, Gualandi F, Baciqalupo A, Sambuceti G, Sacchi N et al. The intra-bone route of administration of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic disease. Best Pract Res Clin Haematol 2010; 23: 237–244.

    Article  PubMed  Google Scholar 

  19. Delaney C, Heimfeld S, Branshem-Stein C, Voorhies H, Manger RL, Bernstein ID . Notch mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16: 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 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 Cl Ha 2010; 23: 259–274.

    Article  Google Scholar 

  21. Chou S, Chu P, Hwang W, Lodish H . Expansion of human cord blood hematopoietic stem cells for transplantation. Cell Stem Cell 2010; 7: 427–428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Delaney C, Ratajczak MZ, Laughlin MJ . Strategies to enhance umbilical cord blood stem cell engraftment in adult patients. Expert Rev hematol 2010; 3: 273–283.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fernandez MN, Regidor C, Cabrera R, Garcia-Marco JA, Briz M, Fores R et al. Cord blood transplants: early recovery of neurtophils from co-transplanted sibling hapoidentical progenitor cells and lack of engraftment of cultured cord blood cells as ascertained by analysis of DNA polymorphisms. Bone Marrow Transplant 2001; 28: 355–363.

    Article  CAS  PubMed  Google Scholar 

  25. Magro E, Regidor C, Cabrera R, Sanjuan I, Fores R, Fernandez MN et al. Early hematopoietic recovery after single unit unrelated cord blood transplantation in adults induced by co-infusion of mobilized stem cells from a third party donor. Haematologica 2006; 91: 640–648.

    PubMed  Google Scholar 

  26. 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, 365–373.

    Article  PubMed  Google Scholar 

  27. 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 cotransplantation 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 

  28. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant 2006; 38: 291–297.

    Article  PubMed  Google Scholar 

  29. Liu D, Huang X, Liu K, Xu L, Chen H, Han W et al. Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. Biol Blood Marrow Transplant 2008; 14: 469–477.

    Article  CAS  PubMed  Google Scholar 

  30. Koh LP, Rizzieri DA, Chao NJ . Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors. Biol Blood Marrow Transplant 2007; 13: 1249–1267.

    Article  CAS  PubMed  Google Scholar 

  31. Chen SH, Li X, Huang XJ . Effect of recombinant human granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect. Int J Hematol 2004; 79: 178–184.

    Article  CAS  PubMed  Google Scholar 

  32. Jun HX, Jun CY, Yu ZX . In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor. Haematologica 2004; 89: 1517–1524.

    CAS  PubMed  Google Scholar 

  33. Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Bio Blood Marrow Transplant 2012; 18: 1835–1844.

    Article  Google Scholar 

  34. Wang Y, Chen F, Han Y, Fu ZZ, Tang XW, Miao M et al. Partially matched related hematopoietic stem cell transplantation without ex vivo T cell depletion compared with matched unrelated transplantation in adult patients with hematologic malignancies. Bio Blood Marrow Transplant 2009; 15: 1258–1264.

    Article  CAS  Google Scholar 

  35. Reisner Y, Hagin D, Martelli MF . Haploidentical hematopoietic transplantation: current status and future perspectives. Blood 2011; 118: 6006–6017.

    Article  CAS  PubMed  Google Scholar 

  36. Kanda J, Chao NJ, Rizzieri DA . Haploidentical transplantation for leukemia. Curr Oncol Rep 2010; 12: 292–301.

    Article  PubMed  Google Scholar 

  37. Bayraktar UD, Champlin RE, Ciurea SO . Progress in haploidentical stem cell transplantation. Biol Blood Marrow Transplant 2012; 18: 372–380.

    Article  PubMed  Google Scholar 

  38. Hu YX, Cui Q, Liang B, Huang H . Relapsing hematologic malignancies after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17: 1099–1111.

    Article  PubMed  Google Scholar 

  39. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK et al. Haploidentcial transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Bio Blood Marrow Transplant 2012; 18: 1859–1866.

    Article  Google Scholar 

  40. 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 2012; 119: 1972–1980.

    Article  CAS  PubMed  Google Scholar 

  41. 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 in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23: 3447–3454.

    Article  PubMed  Google Scholar 

  42. 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 

  43. 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 

  44. Barker JN, Scaradavou A, Stevens CE . Combined effect of tatal nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematological malignancies. Blood 2010; 115: 1843–1849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 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: 757–765.

    Article  Google Scholar 

  46. Kalaycio M, Bolwell B, Rybicki L, Absi a, Andresen S, Pohlman B et al. BU-versus TBI- based conditioning for adult patients with ALL. Bone Marrow Transplant 2011; 46: 1413–1417.

    Article  CAS  PubMed  Google Scholar 

  47. Shi-Xia X, Xian-Hua T, Hai-Qin X, Bo F, Xiang-Feng T . Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis. Leuk Lymphoma 2010; 51: 50–60.

    Article  PubMed  Google Scholar 

  48. Kroger N, Zabelina T, Kruger W, Renges H, Stute N, Kabisch H et al. Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients. Bone Marrow Transplant 2001; 27: 349–354.

    Article  CAS  PubMed  Google Scholar 

  49. Gupta T, Kannan S, Dantkale V, Laskar S . Cyclophosphamide plus total body irradiation compared with busulfan cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: a systematic review and meta-analysis. Hematol Oncol Stem Cell Ther 2011; 4: 17–29.

    Article  CAS  PubMed  Google Scholar 

  50. Uberti JP, Agovi MA, Tarima S, Haagenson M, Gandham S, Anasetti C et al. Comparative analysis of BU and CY versus CY and TBI in full intensity unrelated marrow donor transplantation for AML, CML and myelodysplasia. Bone Marrow Transplant 2011; 46: 34–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all of the physicians, nurses, and support personnel for their unevaluated contribution to this study, and we also extend our gratitude to all the patients in this study. This study was supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, as well as Jiangsu Province’s Key Medical Center (ZX201102).

Author information

Authors and Affiliations

  1. Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China

    J Chen, R-X Wang, F Chen, A-N Sun, H-Y Qiu, Z-M Jin, X-W Tang, Y Han, Z-Z Fu, G-S He, M Miao, X Ma & D-P Wu

  2. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, China

    J Chen, R-X Wang, F Chen, A-N Sun, H-Y Qiu, Z-M Jin, X-W Tang, Y Han, Z-Z Fu, G-S He, M Miao, X Ma & D-P Wu

Authors
  1. J Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R-X Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A-N Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H-Y Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z-M Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. X-W Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Z-Z Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G-S He
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. X Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D-P Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D-P Wu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, J., Wang, RX., Chen, F. et al. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transplant 49, 206–211 (2014). https://doi.org/10.1038/bmt.2013.154

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2013.154

Keywords

This article is cited by

Search

Advanced search

Quick links