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:

Donor Selection

Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor

Bone Marrow Transplantation volume 42, pages 643–648 (2008)Cite this article

Abstract

The aim was to evaluate two transplant strategies for patients who lack HLA-identical donors, namely HLA-A, HLA-B or -DRβ1 mismatched unrelated donor (MM URD) transplants (n=14) and umbilical cord blood transplants (UCB, n=27). Diagnosis, disease stage and age were similar in the two groups. Cell dose was lower in the UCB group (P<0.001). Median time to ANC of >0.5 × 109/l was 30 days in the UCB group and 17 days in the MM URD group (P=0.002). Engraftment of plt was delayed in the UCB group (P=0.03). The UCB patients required fewer erythrocyte transfusions (P=0.001). At 100 days, complete donor chimerism for CD3 was 63 and 44% in the UCB and MM URD groups, respectively. Acute GVHD of grades II–IV were 30% in the UCB group and 21% in the MM URD group. The corresponding figures for chronic GVHD were 9 and 20%, respectively. TRM was 30% in the UCB patients and 50% in the MM URD patients. Three-year survival was 66% in the UCB group and 14% in the MM URD group (P=0.006). Although the material is small and heterogeneous, engraftment was delayed, leukocyte chimerism was not significantly different and survival was superior using UCB rather than MM URD transplants.

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

Similar content being viewed by others

References

  1. Beatty PG, Hansen JA, Longton GM, Thomas ED, Sanders JE, Martin PJ et al. Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 1991; 51: 443–447.

    Article  CAS  Google Scholar 

  2. Ringdén O . Bone marrow transplantation using unrelated donors for haematological malignancies. Med Oncol 1997; 14: 11–22.

    Article  Google Scholar 

  3. Kiehl MG, Kraut L, Schwerdtfeger R, Hertenstein B, Remberger M, Kroeger N et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission. J Clin Oncol 2004; 22: 2816–2825.

    Article  Google Scholar 

  4. Petersdorf EW, Anasetti C, Martin PJ, Hansen JA . Tissue typing in support of unrelated hematopoietic cell transplantation. Tissue Antigens 2003; 61: 1–11.

    Article  CAS  Google Scholar 

  5. Ringden O, Schaffer M, Le Blanc K, Persson U, Hauzenberger D, Abedi MR et al. Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers? Biol Blood Marrow Transplant 2004; 10: 128–134.

    Article  Google Scholar 

  6. 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  Google Scholar 

  7. 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  Google Scholar 

  8. Cohena Y, Nagler A . Hematopoietic stem-cell transplantation using umbilical-cord blood. Leuk Lymphoma 2003; 44: 1287–1299.

    Article  Google Scholar 

  9. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  11. Tse W, Laughlin M . Cord blood transplantation in adult patients. Cytotherapy 2005; 7: 228–242.

    Article  CAS  Google Scholar 

  12. Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood 1996; 88: 795–802.

    CAS  PubMed  Google Scholar 

  13. Wall DA, Carter SL, Kernan NA, Kapoor N, Kamani NR, Brochstein JA et al. Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience. Biol Blood Marrow Transplant 2005; 11: 637–646.

    Article  CAS  Google Scholar 

  14. 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  Google Scholar 

  15. 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  Google Scholar 

  16. Ringden O, Soderdahl G, Mattsson J, Uzunel M, Remberger M, Hentschke P et al. Transplantation of autologous and allogeneic bone marrow with liver from a cadaveric donor for primary liver cancer. Transplantation 2000; 69: 2043–2048.

    Article  CAS  Google Scholar 

  17. Ringden O, Ruutu T, Remberger M, Nikoskelainen J, Volin L, Vindelov L et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood 1994; 83: 2723–2730.

    CAS  PubMed  Google Scholar 

  18. Oakhill A, Pamphilon DH, Potter MN, Steward CG, Goodman S, Green A et al. Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission. Br J Haematol 1996; 94: 574–578.

    Article  CAS  Google Scholar 

  19. Remberger M, Svahn BM, Mattsson J, Ringden O . Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation 2004; 78: 122–127.

    CAS  PubMed  Google Scholar 

  20. Ringden O, Remberger M, Persson U, Ljungman P, Aldener A, Andstrom E et al. Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings. Bone Marrow Transplant 1995; 15: 619–625.

    CAS  PubMed  Google Scholar 

  21. Maris MB, Sandmaier BM, Storer BE, Maloney DG, Shizuru JA, Agura E et al. Unrelated donor granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell transplantation after nonmyeloablative conditioning: the effect of postgrafting mycophenolate mofetil dosing. Biol Blood Marrow Transplant 2006; 12: 454–465.

    Article  CAS  Google Scholar 

  22. Cutler C, Kim HT, Hochberg E, Ho V, Alyea E, Lee SJ et al. Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 328–336.

    Article  CAS  Google Scholar 

  23. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.

    Article  CAS  Google Scholar 

  24. Svahn BM, Remberger M, Myrback KE, Holmberg K, Eriksson B, Hentschke P et al. Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood 2002; 100: 4317–4324.

    Article  CAS  Google Scholar 

  25. Remberger M, Naseh N, Aschan J, Barkholt L, LeBlanc K, Svennberg P et al. G-CSF given after haematopoietic stem cell transplantation using HLA-identical sibling donors is associated to a higher incidence of acute GVHD II–IV. Bone Marrow Transplant 2003; 32: 217–223.

    Article  CAS  Google Scholar 

  26. Mattsson J, Uzunel M, Tammik L, Aschan J, Ringden O . Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation. Leukemia 2001; 15: 1976–1985.

    Article  CAS  Google Scholar 

  27. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C et al. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 2002; 99: 4618–4625.

    Article  CAS  Google Scholar 

  28. Ringden O, Klaesson S, Sundberg B, Ljungman P, Lonnqvist B, Persson U . Decreased incidence of graft-versus-host disease and improved survival with methotrexate combined with cyclosporin compared with monotherapy in recipients of bone marrow from donors other than HLA identical siblings. Bone Marrow Transplant 1992; 9: 19–25.

    CAS  PubMed  Google Scholar 

  29. Marmont AM, Horowitz MM, Gale RP, Sobocinski K, Ash RC, van Bekkum DW et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  30. Remberger M, Sundberg B . Rabbit-immunoglobulin G levels in patients receiving thymoglobulin as part of conditioning before unrelated donor stem cell transplantation. Haematologica 2005; 90: 931–938.

    CAS  PubMed  Google Scholar 

  31. Sundin M, Le Blanc K, Ringden O, Barkholt L, Omazic B, Lergin C et al. The role of HLA mismatch, splenectomy and recipient Epstein-Barr virus seronegativity as risk factors in post-transplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation. Haematologica 2006; 91: 1059–1067.

    PubMed  Google Scholar 

  32. Gustafsson A, Levitsky V, Zou JZ, Frisan T, Dalianis T, Ljungman P et al. Epstein–Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood 2000; 95: 807–814.

    CAS  PubMed  Google Scholar 

  33. Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.

    Article  CAS  Google Scholar 

  34. Bradley MB, Satwani P, Baldinger L, Morris E, van de Ven C, Del Toro G et al. Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases. Bone Marrow Transplant 2007; 40: 621–631.

    Article  CAS  Google Scholar 

  35. 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  Google Scholar 

  36. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A 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: 1947–1954.

    Article  Google Scholar 

Download references

Acknowledgements

We thank the staff at the Centre for Allogeneic Stem Cell Transplantation, Departments of Hematology and Pediatrics, for competent and compassionate care of the patients. We thank Inger Hammarberg for the preparation of the manuscript. This study was supported by grants from the Swedish Cancer Society (0070-B06-20XBC), the Children's Cancer Foundation (06/094), the Swedish Research Council (K2007-64X-05971-27-1), the Cancer Society in Stockholm, the Cancer and Allergy Foundation and Karolinska Institutet.

Author information

Authors and Affiliations

  1. Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden

    O Ringdén, M Okas, M Uhlin, M Uzunel, M Remberger & J Mattsson

Authors
  1. O Ringdén
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Okas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Uhlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Uzunel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Remberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Mattsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O Ringdén.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ringdén, O., Okas, M., Uhlin, M. et al. Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. Bone Marrow Transplant 42, 643–648 (2008). https://doi.org/10.1038/bmt.2008.239

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.239

Keywords

This article is cited by

Search

Advanced search

Quick links