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.

  • Letter to the Editor
  • Published:

Twenty-year follow-up of a randomized trial comparing intraosseous and i.v. BM transplantation

Bone Marrow Transplantation volume 49, pages 1541–1542 (2014)Cite this article

Subjects

In 1998, we reported a randomized study comparing intraosseous (i.o.) and i.v. transplantation of allogeneic haematopoietic stem cells.1 The conclusion of that study was that i.o. infusion of BM cells could be done safely.

In our 1998 study, 38 patients were transplanted with BM from sibling donors (i.o. (n=8), i.o.+ i.v. (n=10) and i.v. (n=20)). The majority of the patients had acute or chronic leukaemia (33/38). The transplantation procedure with conditioning, immunosuppression and supportive care has been described previously in detail.2 In the patients receiving i.o. infusion, median follow-up time was 19.3 (18.4–20.5) years and in the i.v. group the corresponding value was 19.0 (18.4–20.6) years. In the initial report, there were no differences in time to reach a neutrophil count of >0.5 × 109/L, in time to reach platelet engraftment of >30 × 109/L, in transfusions of erythrocytes or platelets, in probability of acute GVHD of grades II–IV, or in chronic GVHD.1 TRM, probability of relapse and leukaemia-free survival at 2 years were not significantly different between the two groups. The i.o. group needed fewer days with total parenteral nutrition (P=0.03). There were no patients with bacteraemia during the first 30 days in the i.o. group, as opposed to six patients in those given BM grafts i.v. (P=0.02). Because of the low risk of bacteraemia with i.o. infusion, we decided to include this approach in later patients. However, four consecutive patients who received i.o. BM infusion after this trial had ended all developed coagulase-negative staphylococcal septicaemia. After that, all patients received their graft i.v. Most importantly, technetium scintigraphy using antigranulocyte monoclonal Ab showed that there was no difference in activity in the skeleton, and distribution of marked BM granulocytes was the same after i.o. or i.v. infusion.

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

References

  1. 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 

  2. 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 

  3. Ringden O, Remberger M, Runde V, Bornhauser M, Blau IW, Basara N et al. Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation. Blood 1999; 94: 455–464.

    CAS  PubMed  Google Scholar 

  4. Castello S, Podesta M, Menditto VG, Ibatici A, Pitto A, Figari O et al. Intra-bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency. Exp Hematol 2004; 32: 782–787.

    Article  PubMed  Google Scholar 

  5. Klimczak A, Unal S, Jankowska A, Coburn C, Siemionow M Donor-origin cell engraftment after intraosseous or intravenous bone marrow transplantation in a rat model. Bone Marrow Transplant 2007; 40: 373–380.

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Fukui J, Inaba M, Ueda Y, Miyake T, Hosaka N, Kwon AH et al. Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells. Stem Cells 2007; 25: 1595–1601.

    Article  CAS  PubMed  Google Scholar 

  8. Nakamura K, Inaba M, Sugiura K, Yoshimura T, Kwon AH, Kamiyama Y et al. Enhancement of allogeneic hematopoietic stem cell engraftment and prevention of GVHD by intra-bone marrow bone marrow transplantation plus donor lymphocyte infusion. Stem Cells 2004; 22: 125–134.

    Article  PubMed  Google Scholar 

  9. Ramirez PA, Wagner JE, Brunstein CG . Going straight to the point: intra-BM injection of hematopoietic progenitors. Bone Marrow Transplant 2010; 45: 1127–1133.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Staff of the Centre for Allogeneic Stem Cell Transplantation for compassionate and competent care of the patients. We also thank Inger Holmström for expert help in preparation of the manuscript. This study was supported by grants to OR from the Swedish Cancer Foundation (12 0506), the Swedish Research Council (K2011-64X-05971-31-6), the Children’s Cancer Foundation (PROJ12/021), Stockholm County Council, the Stockholm Cancer Foundation and Karolinska Institutet.

Author information

Author notes

  1. H Hägglund

    Present address: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.,

Authors and Affiliations

  1. Haematology Centre, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    H Hägglund

  2. Division of Therapeutic Immunology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    M Remberger & O Ringden

  3. Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    M Remberger & O Ringden

Authors
  1. H Hägglund
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Remberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O Ringden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O Ringden.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hägglund, H., Remberger, M. & Ringden, O. Twenty-year follow-up of a randomized trial comparing intraosseous and i.v. BM transplantation. Bone Marrow Transplant 49, 1541–1542 (2014). https://doi.org/10.1038/bmt.2014.184

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.184

Search

Advanced search

Quick links