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

Intra-BM injection to enhance engraftment after myeloablative umbilical cord blood transplantation with two partially HLA-matched units

Bone Marrow Transplantation volume 43, pages 935–940 (2009)Cite this article

Abstract

The time to neutrophil engraftment for adult patients after myeloablative double unit umbilical cord blood (UCB) transplantation is 23 days when the two units are given i.v. We hypothesized that the intra-BM injection (IBMI) of one of the two UCB units would reduce systemic loss of hematopoietic progenitors and shorten time to neutrophil recovery after myeloablation. Ten patients with a median age of 35 years were transplanted. The unit to be given by IBMI was randomly assigned; the other unit was given i.v. The median infused graft total nucleated cell dose was 3.7 × 107/kg with no difference between i.v. and IBMI units. All patients tolerated the procedure well, and there was no severe adverse event related to IBMI. The median time to neutrophil engraftment and plt recovery >50 000/μl was 21 and 69 days, respectively. In all, 9 of 10 patients engrafted, 5 with the i.v. unit and 4 with the IBMI unit; 7 of 8 evaluable patients developed acute GVHD and 5 of 10 patients died from treatment-related causes. Survival was 47% at 1 year. Despite safety of administration, IBMI of one of two UCB units did not shorten the time to neutrophil engraftment and offers no advantage over conventional double unit transplantation.

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. 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 

  2. 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 

  3. 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 

  4. Wagner JE . A new route to the stem-cell niche. Lancet Oncol 2008; 9: 812–814.

    Article  PubMed  Google Scholar 

  5. Zhong JF, Zhan Y, Anderson WF, Zhao Y . Murine hematopoietic stem cell distribution and proliferation in ablated and nonablated bone marrow transplantation. Blood 2002; 100: 3521–3526.

    Article  CAS  PubMed  Google Scholar 

  6. Wang J, Kimura T, Asada R, Harada S, Yokota S, Kawamoto Y et al. SCID-repopulating cell activity of human cord blood-derived CD34− cells assured by intra-bone marrow injection. Blood 2003; 101: 2924–2931.

    Article  CAS  PubMed  Google Scholar 

  7. Kushida T, Inaba M, Hisha H, Ichioka N, Esumi T, Ogawa R et al. Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice. Blood 2001; 97: 3292–3299.

    Article  CAS  PubMed  Google Scholar 

  8. Mazurier F, Doedens M, Gan OI, Dick JE . Rapid myeloerythroid repopulation after intrafemoral transplantation of NOD-SCID mice reveals a new class of human stem cells. Nat Med 2003; 9: 959–963.

    Article  CAS  PubMed  Google Scholar 

  9. Yahata T, Ando K, Sato T, Miyatake H, Nakamura Y, Muguruma Y et al. A highly sensitive strategy for SCID-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID mice bone marrow. Blood 2003; 101: 2905–2913.

    Article  CAS  PubMed  Google Scholar 

  10. Cui J, Wahl RL, Shen T, Fisher SJ, Recker E, Ginsburg D et al. Bone marrow cell trafficking following intravenous administration. Br J Haematol 1999; 107: 895–902.

    Article  CAS  PubMed  Google Scholar 

  11. Hagglund H, Ringden O, Agren B, Wennberg L, Remberger M, Rundquist L et al. Intraosseous compared to intravenous infusion of allogeneic bone marrow. Bone Marrow Transplant 1998; 21: 331–335.

    Article  CAS  PubMed  Google Scholar 

  12. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.

    Article  CAS  PubMed  Google Scholar 

  13. Rubinstein P, Dobrila L, Rosenfield RE, Adamson JW, Migliaccio G, Migliaccio AR et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc Natl Acad Sci USA 1995; 92: 10119–10122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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  PubMed  PubMed Central  Google Scholar 

  15. 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 

  16. Lin DY . Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med 1997; 16: 901–910.

    Article  CAS  PubMed  Google Scholar 

  17. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  18. Frassoni F, Gualandi F, Podesta M, Raiola AM, Ibatici A, Piaggio G et al. Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. Lancet Oncol 2008; 9: 831–839.

    Article  CAS  PubMed  Google Scholar 

  19. Ibatici A, Raiola AM, Podestà M, Gualandi F, Sessarego N, Parodi A et al. Direct intra-bone marrow injection of unrelated umbilical cord blood cells overcomes the problem of delayed engarftment and improves the feasibility of hematopoietic transplant in adult patients. Blood 2007; 110: 105a.

    Google Scholar 

  20. Khoury HJ, Loberiza Jr FR, Ringden O, Barrett AJ, Bolwell BJ, Cahn JY et al. Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation. Blood 2006; 107: 1712–1716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Brunstein CG, Defor T, Wagner JE . Umbilical cord blood transplantation (UCBT) at the university of Minnesota: impact of double unit and fludarabine on engraftment after myeloablative conditioning. Blood 2006; 108: 888a.

    Article  Google Scholar 

  22. 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 

  23. MacMillan M, Weisdorf DJ, Brunstein CG, Cao Q, Defor T, Verneris MR et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood 2008; e-pub ahead of print 7 November 2008.

  24. Slayton WB, Li XM, Butler J, Guthrie SM, Jorgensen ML, Wingard JR et al. The role of the donor in the repair of the marrow vascular niche following hematopoietic stem cell transplant. Stem Cells 2007; 25: 2945–2955.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Marilee Larkin and Kathy Gulberg for their assistance with patient recruiting, clinical monitoring and the execution of the IBMI procedure. This work was supported in part by grants from the National Cancer Institute PO1-CA65493 (JEW, TED), The Children's Cancer Research Fund (JEW, TED), and the National Marrow Donor Program Prime Award #13468 (JNB)

Author information

Authors and Affiliations

  1. University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA

    C G Brunstein, J N Barker, D J Weisdorf, T E DeFor, S Y Chong, J S Miller, P B McGlave & J E Wagner

  2. Division of Medical Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    C G Brunstein, J N Barker, D J Weisdorf, J S Miller & P B McGlave

  3. Division of Pediatric Hematology Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    T E DeFor & J E Wagner

  4. Molecular and Cellular Therapy Laboratory, University of Minnesota, Minneapolis, MN, USA

    D McKenna

Authors
  1. C G Brunstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J N Barker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D J Weisdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T E DeFor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D McKenna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Y Chong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J S Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P B McGlave
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J E Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C G Brunstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunstein, C., Barker, J., Weisdorf, D. et al. Intra-BM injection to enhance engraftment after myeloablative umbilical cord blood transplantation with two partially HLA-matched units. Bone Marrow Transplant 43, 935–940 (2009). https://doi.org/10.1038/bmt.2008.417

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.417

Keywords

This article is cited by

Search

Advanced search

Quick links