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:

Immunobiology

Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions

Abstract

Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD. Bone Marrow Transplantation (2001) 28, 581–586.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Hows J, Beddow K, Gordon-Smith E . Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation Blood 1986 67: 177–181

    CAS  PubMed  Google Scholar 

  2. Klumpp TR . Immunohaematologic complications of bone marrow transplantation Bone Marrow Transplant 1991 8: 159–170

    CAS  PubMed  Google Scholar 

  3. Klumpp TR, Caligiuri MA, Rabinowe SN et al. Autoimmune pancytopenia following allogeneic bone marrow transplantation Bone Marrow Transplant 1990 6: 445–447

    CAS  PubMed  Google Scholar 

  4. De Lord C, Marsh JCW, Smith JG et al. Fatal autoimmune pancytopenia following bone marrow transplantation foraplastic anaemia Bone Marrow Transplant 1996 18: 237–239

    CAS  PubMed  Google Scholar 

  5. Bashey A, Owen I, Lucas GF . Late onset immune pancytopenia following bone marrow transplantation Br J Haematol 1991 78: 268–274

    Article  CAS  PubMed  Google Scholar 

  6. Chen FE, Owen I, Savage D et al. Late onset haemolysis and red cell autoimmunisation after allogeneic bone marrow transplant Bone Marrow Transplant 1997 19: 491–495

    Article  CAS  PubMed  Google Scholar 

  7. Drobyski WR, Potluri J, Sauer D, Gottschall JL . Autoimmune hemolytic anemia following T cell-depleted allogeneic allogeneic bone marrow transplantation Bone Marrow Transplant 1996 17: 1093–1099

    CAS  PubMed  Google Scholar 

  8. Drobyski W, Ash R, Casper J . Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukaemia Blood 1994 83: 1980–1987

    CAS  PubMed  Google Scholar 

  9. Spencer A, Szydlo RM, Brookes PA et al. Bone marrow transplantation for chronic myeloid leukaemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA Class I identity between donor and recipient Blood 1995 86: 3590–3597

    CAS  PubMed  Google Scholar 

  10. Spencer A, Brookes PA, Kaminski E et al. Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors Transplantation 1995 59: 1302–1308

    Article  CAS  PubMed  Google Scholar 

  11. Sehn LH, Aleya EP, Canning C et al. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion J Clin Oncol 1999 17: 561–568

    Article  CAS  PubMed  Google Scholar 

  12. Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients Blood 1995 86: 2041–2050

    CAS  PubMed  Google Scholar 

  13. Lawler M, Humphries P, McCann SR . Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction Blood 1991 77: 2504–2514

    CAS  PubMed  Google Scholar 

  14. Mackinnon S, Barnett L, Heller G, O'Reilly RJ . Minimal residual disease is more common in patients who have mixed T cell chimerism after bone marrow transplantation for chronic myelogenous leukaemia Blood 1994 83: 3409–3416

    CAS  PubMed  Google Scholar 

  15. Roux E, Abdi K, Speiser D et al. Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell depleted bone marrow: involvement of different hematological lineages before and after relapse Blood 1993 81: 243–248

    CAS  PubMed  Google Scholar 

  16. Serrano J, Roman J, Sanchez J et al. Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210BCR-ABL and p190BCR-ABL after allogeneic bone marrow transplantation for chronic myeloidleukemia: increasing mixed myeloid chimerism and p190BCR-ABL detection precede cytogenetic relapse Blood 2000 95: 2659–2665

    CAS  PubMed  Google Scholar 

  17. Lin F, van Rhee F, Goldman JM, Cross NCP . Kinetics of increasing BCR-ABL transcript numbers in chronic myeloid leukaemia patients who relapse after bone marrow transplantation Blood 1996 87: 4473–4478

    CAS  PubMed  Google Scholar 

  18. Gardiner N, Lawler M, O'Riordan JM et al. Monitoring of lineage-specific chimerism allows early prediction of response following donor lymphocyte infusions for relapsed chronic myeloid leukaemia Bone Marrow Transplant 1998 21: 711–719

    Article  CAS  PubMed  Google Scholar 

  19. Gardiner N, McCann SR, O'Riordan J, Lawler M . Chimerism following donor lymphocyte infusion for chronic myeloid leukemia Blood 1999 93: 2748–2749

    CAS  PubMed  Google Scholar 

  20. Craddock C, Szydlo RM, Dazzi F et al. CMV serostatus is a major determinant of outcome after T depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored GVHD prophylaxis Br J Haematol 2001 112: 228–236

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Cross N, Lin F, Chase A . Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukaemia after bone marrow transplantation Blood 1993 82: 1929–1936

    CAS  PubMed  Google Scholar 

  24. Hochhaus A, Lin F, Reiter A et al. Quantification of residual disease in chronic myelogenous leukemia patients on interferon-alpha therapy by competitive polymerase chain reaction Blood 1996 87: 1549–1555

    CAS  PubMed  Google Scholar 

  25. Dacie JV, Lewis SME . Practical Haematology Churchill Livingstone: London 1995

    Google Scholar 

  26. Dazzi F, Szydlo RM, Craddock C et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia Blood 2000 95: 67–71

    CAS  PubMed  Google Scholar 

  27. Moller G . Models of autoimmunity Immunol Rev 1990 118: 1–310

    Google Scholar 

  28. Mason D, Powrie F . Control of immune pathology by regulatory T cells Curr Opin Immunol 1998 10: 649–655

    Article  CAS  PubMed  Google Scholar 

  29. Dumont-Girard F, Roux E, van Lier RA et al. Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants Blood 1998 92: 4464–4471

    CAS  PubMed  Google Scholar 

  30. Mackall CM, Fleischer T, Brown M et al. Age, thymopoiesis and CD4+ T lymphocyte regeneration following chemotherapy New Engl J Med 1995 332: 143–149

    Article  CAS  PubMed  Google Scholar 

  31. Douek DC, McFarland RD, Keiser PH et al. Changes in thymic function with age and during the treatment of HIV infection Nature 1998 396: 690–695

    Article  CAS  PubMed  Google Scholar 

  32. Wu CJ, Chillemi A, Alyea EP et al. Reconstitution of the T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism Blood 2000 95: 352–359

    CAS  PubMed  Google Scholar 

  33. Hale G, Zhang M, Bunjes D et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection Blood 1998 92: 4581–4590

    CAS  PubMed  Google Scholar 

  34. Dazzi F, Szydlo RM, Cross NCP et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia Blood 2000 96: 2712–2716

    CAS  PubMed  Google Scholar 

  35. Claret EJ, Alyea EP, Orsini E et al. Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion J Clin Invest 1997 100: 855–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cwynarski, K., Goulding, R., Pocock, C. et al. Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions. Bone Marrow Transplant 28, 581–586 (2001). https://doi.org/10.1038/sj.bmt.1703206

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703206

Keywords

This article is cited by

Search

Quick links