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:

Post-Transplant Events

Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath ‘in the bag’ as T-cell depletion: the Leiden experience

Bone Marrow Transplantation volume 37, pages 1129–1134 (2006)Cite this article

Abstract

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT) but can be prevented by removing T-lymphocytes from the graft. Campath (anti-CD52) antibodies have been widely used in vivo for T-cell depletion following conventional and reduced intensity conditioning regimens. The use of Campath in vivo was associated with a significant reduction in GVHD but at the cost of impaired immune reconstitution. We evaluated the long-term outcome of 73 myeloablative allogeneic stem cell transplants with HLA-identical sibling donors using Campath ‘in the bag’ as method of in vitro T-cell depletion. All patients engrafted and hematopoietic recovery was uneventful, resulting in a median of 99% donor chimerism at 3 months after alloSCT. Cytomegalovirus (CMV) reactivation occurred in 53% of the patients. No CMV disease was observed probably as a result of pre-emptive (val)ganciclovir treatment. The incidence of aGVHD was low (22% grade II). No grades III–IV aGVHD was observed and extensive chronic GVHD (cGVHD) occurred in 19% of the patients. The low incidence of GVHD and successful pre-emptive antiviral therapy resulted in low TRM of 8%. Sixteen patients died due to disease relapse after alloSCT, resulting in an overall survival of 48% at 5-years after alloSCT.

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. 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 

  2. Baron F, Storb R . Allogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review. Springer Semin Immunopathol 2004; 26: 71–94.

    Article  Google Scholar 

  3. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED . Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1533.

    Article  CAS  Google Scholar 

  4. Barrett AJ, Malkovska V . Graft-versus-leukemia: understanding and using the alloimmune response to treat haematological malignancies. Br J Haematol 1996; 93: 754–761.

    Article  CAS  Google Scholar 

  5. Ruutu T, Niederwieser D, Gratwohl A, Apperley JF . A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow Transplantation (EBMT). Chronic Leukaemia Working Party of the EBMT. Bone Marrow Transplant 1997; 19: 759–764.

    Article  CAS  Google Scholar 

  6. Urbano-Ispizua A, Garcia-Conde J, Brunet S, Hernandez F, Sanz G, Petit J et al. High incidence of chronic graft versus host disease after allogeneic peripheral blood progenitor cell transplantation. The Spanish Group of Allo-PBPCT. Haematologica 1997; 82: 683–689.

    CAS  PubMed  Google Scholar 

  7. Barge RMY, Brouwer RE, Beersma MFC, Starrenburg CW, Zwinderman AH, Hale G et al. Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short and long-term outcome. Bone Marrow Transplant 2001; 27: 1053–1058.

    Article  CAS  Google Scholar 

  8. Barge RMY, Osanto S, Marijt WAF, Starrenburg CW, Fibbe WE, Nortier JW et al. Minimal GvHD following in vitro T cell-depleted allogeneic stem cell transplantation with reduced-intensity conditioning allowing subsequent infusions of donor lymphocytes in patients with hematological malignancies and solid tumors. Exp Hematol 2003; 31: 865–872.

    Article  CAS  Google Scholar 

  9. Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S et al. In vivo CAMPATH-1H prevents GvHD following nonmyeloablative stem-cell transplantation. Cytotherapy 2001; 3: 197–201.

    Article  CAS  Google Scholar 

  10. Hale G, Waldmann H, for CAMPATH users. Control of graft-versus-host disease and graft rejection by T cell depletion of donor and recipient with CAMPATH-1 antibodies. Results of matched sibling transplants for malignant diseases. Bone Marrow Transplant 1994; 13: 597–611.

    CAS  Google Scholar 

  11. Hale G, Waldmann H, for CAMPATH users. CAMPATH-1 monoclonal antibodies in bone marrow transplantation. J Hematotherapy 1994; 3: 15–31.

    Article  CAS  Google Scholar 

  12. Hale G, Clark M, Waldmann H . Therapeutic potential of rat monoclonal antibodies: isotype specificity of antibody-dependent cell-mediated cytotoxicity with human lymphocytes. J Immunol 1985; 134: 3056–3061.

    CAS  PubMed  Google Scholar 

  13. Chakrabarti S, MacDonald D, Hale G, Holder K, Turner V, Czarnecka H et al. T-cell depletion with Campath-1H ‘in the bag’ for matched related allogeneic peripheral blood stem cell transplantation is associated with reduced graft-versus-host disease, rapid immune constitution and improved survival. Br J of Haematol 2003; 121: 109–118.

    Article  Google Scholar 

  14. Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O' Gorman P et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 2002; 99: 4357–4363.

    Article  CAS  Google Scholar 

  15. Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH et al. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood 2003; 102: 404–406.

    Article  CAS  Google Scholar 

  16. Boeckh M, Gooley TH, Myerson D, Cunningham T, Schoch G, Bowden RA . Cytomegalovirus pp65 antigenemia-guided early treatment with Ganciclovir versus Ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood 1996; 88: 4063–4071.

    CAS  PubMed  Google Scholar 

  17. Kalpoe JS, Kroes AC, de Jong MD, Schinkel J, de Brouwer CS, Beersma MF et al. Validation of clinical application of cytomegalovirus plasma DNA load measurement and definition of treatment criteria by analysis of correlation to antigen detection. J Clin Microbiol 2004; 42: 1498–1504.

    Article  CAS  Google Scholar 

  18. Glucksberg H, Storb R, Fefer A . Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  Google Scholar 

  19. Shulman HM, Sullivan KM, Weiden PL . Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  Google Scholar 

  20. Posthuma EF, Marijt EW, Barge RM, van Soest RA, Baas IO, Starrenburg CW et al. Alpha-interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease. Biol Blood Marrow Transplant 2004; 10: 204–212.

    Article  CAS  Google Scholar 

  21. Falkenburg JHF, Wafelman AR, Joosten P, Smit WM, van Bergen CA, Bongaerts R et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood 1999; 94: 1201–1208.

    CAS  PubMed  Google Scholar 

  22. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    Article  CAS  Google Scholar 

  23. Couban S, Simpson DR, Barnett MJ, Bredeson C, Hubesch L, Howson-Jan K et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525–1531.

    Article  CAS  Google Scholar 

  24. Hale G, Jacobs P, Wood L, Fibbe WE, Barge R, Novitzky N et al. CD 52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant 2000; 26: 69–76.

    Article  CAS  Google Scholar 

  25. Chakrabarti S, MacDonald D, Milligan DW . T cell-depleted nonmyeloablative stem cell transplantation: what is the optimum balance between the intensity of host conditioning and the degree of T cell depletion of the graft? Bone Marrow Transplant 2001; 28: 313–314.

    Article  CAS  Google Scholar 

  26. Chakrabarti S, Hale G, Waldmann H . Alemtuzumab (Campath-1H) in allogeneic stem cell transplantation: where do we go from here? Transplant Proc 2004; 36: 1225–1227.

    Article  CAS  Google Scholar 

  27. Baron F, Beguin Y . Preemptive cellular immunotherapy after T-cell-depleted allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 351–359.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge Monica Seltenheim and Floor Beaumont for their excellent help in acquiring patient data.

Author information

Authors and Affiliations

  1. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    R M Y Barge, C W J Starrenburg, J H F Falkenburg, W E Fibbe, E W Marijt & R Willemze

Authors
  1. R M Y Barge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C W J Starrenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J H F Falkenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W E Fibbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E W Marijt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Willemze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R M Y Barge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barge, R., Starrenburg, C., Falkenburg, J. et al. Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath ‘in the bag’ as T-cell depletion: the Leiden experience. Bone Marrow Transplant 37, 1129–1134 (2006). https://doi.org/10.1038/sj.bmt.1705385

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705385

Keywords

This article is cited by

Search

Advanced search

Quick links