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.

  • Review
  • Published:

How and when should we monitor chimerism after allogeneic stem cell transplantation?

Bone Marrow Transplantation volume 35, pages 107–119 (2005)Cite this article

Abstract

Summary:

Chimerism analysis has become an important tool for the peri-transplant surveillance of engraftment. It offers the possibility to realize impending graft rejection and can serve as an indicator for the recurrence of the underlying malignant or nonmalignant disease. Most recently, these investigations have become the basis for treatment intervention, for example, to avoid graft rejection, to maintain engraftment and to treat imminent relapse by pre-emptive immunotherapy. This invited review focuses on the clinical implications of characterization of hematopoietic chimerism in stem cell 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
Figure 4

Similar content being viewed by others

References

  1. Trigg ME . Milestones in the development of pediatric hematopoietic stem cell transplantation – 50 years of progress. Pediatr Transplant 2002; 6: 465–474.

    PubMed  Google Scholar 

  2. Appelbaum FR . The current status of hematopoietic cell transplantation. Annu Rev Med 2003; 54: 491–512.

    CAS  PubMed  Google Scholar 

  3. O’Dwyer ME, Mauro MJ, Druker BJ . Recent advancements in the treatment of chronic myelogenous leukemia. Annu Rev Med 2002; 53: 369–381.

    PubMed  Google Scholar 

  4. Barker JN, Wagner JE . Umbilical cord blood transplantation: current state of the art. Curr Opin Oncol 2002; 14: 160–164.

    PubMed  Google Scholar 

  5. Diaz MA, Kanold J, Vicent MG et al. Using peripheral blood progenitor cells (PBPC) for transplantation in pediatric patients: a state-of-the-art review. Bone Marrow Transplant 2000; 26: 1291–1298.

    Article  CAS  PubMed  Google Scholar 

  6. Brodsky RA, Smith BD . Bone marrow transplantation for autoimmune diseases. Curr Opin Oncol 1999; 11: 83–86.

    CAS  PubMed  Google Scholar 

  7. de Lima M, John LS, Wieder ED et al. Double-chimaerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. Br J Haematol 2002; 119: 773–776.

    PubMed  Google Scholar 

  8. Thomas ED . Bone marrow transplantation: a review. Semin Hematol 1999; 36: 95–103.

    CAS  PubMed  Google Scholar 

  9. Rose HJ . A Handbook of Greek Mythology. Routledge: London and New York, 1989.

    Google Scholar 

  10. Anderson D, Billingham RE, Lampkin GH et al. The use of skin grafting to distinguish between monzygotic and dizygotic twins in cattle. Heredity 1951; 5: 379–397.

    Google Scholar 

  11. Ford C . Cytological identification of radiation-chimaeras. Nature 1956; 177: 452–454.

    CAS  PubMed  Google Scholar 

  12. McCann S, Lawler M . Mixed chimerism; detection and significance following BMT. Bone Marrow Transplant 1993; 11: 91–94.

    CAS  PubMed  Google Scholar 

  13. Bader P, Hoelle W, Klingebiel T et al. Quantitative assessment of mixed hematopoietic chimerism by polymerase chain reaction after allogeneic BMT. Anticancer Res 1996; 16: 1759–1763.

    CAS  PubMed  Google Scholar 

  14. Bader P, Hoelle W, Klingebiel T et al. Mixed hematopoietic chimerism after allogeneic bone marrow transplantation: the impact of quantitative PCR analysis for prediction of relapse and graft rejection in children. Bone Marrow Transplant 1997; 19: 697–702.

    CAS  PubMed  Google Scholar 

  15. Ramirez M, Diaz MA, Garcia-Sanchez F et al. Chimerism after allogeneic hematopoietic cell transplantation in childhood acute lymphoblastic leukemia. Bone Marrow Transplant 1996; 18: 1161–1165.

    CAS  PubMed  Google Scholar 

  16. Bader P, Beck J, Schlegel PG et al. Additional immunotherapy on the basis of increasing mixed hematopoietic chimerism after allogeneic BMT in children with acute leukemia: is there an option to prevent relapse? Bone Marrow Transplant 1997; 20: 79–81.

    CAS  PubMed  Google Scholar 

  17. Thiede C, Bornhauser M, Ehninger G . Strategies and clinical implications of chimerism diagnostics after allogeneic hematopoietic stem cell transplantation. Acta Haematol 2004; 112: 16–23.

    PubMed  Google Scholar 

  18. Niethammer D, Goldmann SF, Flad HD et al. Split chimerism in three patients suffering from severe combined immunodeficiency (SCID). Haematol Blood Transfus 1980; 25: 391–401.

    CAS  PubMed  Google Scholar 

  19. Korver K, de Lange GG, van den Bergh RL et al. Lymphoid chimerism after allogeneic bone marrow transplantation. Y-chromatin staining of peripheral T and B lymphocytes and allotyping of serum immunoglobulins. Transplantation 1987; 44: 643–650.

    CAS  PubMed  Google Scholar 

  20. Offit K, Burns JP, Cunningham I et al. Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation. Blood 1990; 75: 1346–1355.

    CAS  PubMed  Google Scholar 

  21. Sparkes R . Cytogenetic analysis in human bone marrow transplantation. Cancer Genet Cytogenet 1981; 4: 345–352.

    CAS  PubMed  Google Scholar 

  22. Schattenberg A, de Witte T, Salden M et al. Mixed hematopoietic chimerism after allogeneic transplantation with lymphocyte-depleted bone marrow is not associated with a higher incidence of relapse. Blood 1989; 73: 1367–1372.

    CAS  PubMed  Google Scholar 

  23. Schaap N, Schattenberg A, Bar B et al. Red blood cell phenotyping is a sensitive technique for monitoring chronic myeloid leukaemia patients after T-cell-depleted bone marrow transplantation and after donor leucocyte infusion. Br J Haematol 2000; 108: 116–125.

    CAS  PubMed  Google Scholar 

  24. Casarino L, Carbone C, Capucci MA et al. Analysis of chimerism after bone marrow transplantation using specific oligonucleotide probes. Bone Marrow Transplant 1992; 10: 165–170.

    CAS  PubMed  Google Scholar 

  25. Knowlton RG, Brown VA, Braman JC et al. Use of highly polymorphic DNA probes for genotypic analysis following bone marrow transplantation. Blood 1986; 68: 378–385.

    CAS  PubMed  Google Scholar 

  26. Yam PY, Petz LD, Knowlton RG et al. Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation. Transplantation 1987; 43: 399–407.

    CAS  PubMed  Google Scholar 

  27. Brunet S, Casals T, Madoz P et al. DNA polymorphisms as implant markers in allogeneic bone marrow transplantation. Preliminary evaluation. Med Clin (Barc) 1989; 93: 765–771.

    CAS  Google Scholar 

  28. Kogler G, Wolf HH, Heyll A et al. Detection of mixed chimerism and leukemic relapse after allogeneic bone marrow transplantation in subpopulations of leucocytes by fluorescent in situ hybridization in combination with the simultaneous immunophenotypic analysis of interphase cells. Bone Marrow Transplant 1995; 15: 41–48.

    CAS  PubMed  Google Scholar 

  29. Petz LD, Yam P, Wallace RB et al. Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies. Blood 1987; 70: 1331–1337.

    CAS  PubMed  Google Scholar 

  30. Bielorai B, Trakhtenbrot L, Amariglio N et al. Multilineage hematopoietic engraftment after allogeneic peripheral blood stem cell transplantation without conditioning in SCID patients. Bone Marrow Transplant 2004; 34: 317–320.

    CAS  PubMed  Google Scholar 

  31. Thiele J, Wickenhauser C, Kvasnicka HM et al. Mixed chimerism of erythro- and megakaryopoiesis following allogeneic bone marrow transplantation. Acta Haematol 2003; 109: 176–183.

    CAS  PubMed  Google Scholar 

  32. Thiele J, Wickenhauser C, Kvasnicka HM et al. Dynamics of lineage-restricted mixed chimerism following sex-mismatched allogeneic bone marrow transplantation. Histol Histopathol 2003; 18: 557–574.

    CAS  PubMed  Google Scholar 

  33. Seong CM, Giralt S, Kantarjian H et al. Early detection of relapse by hypermetaphase fluorescence in situ hybridization after allogeneic bone marrow transplantation for chronic myeloid leukemia. J Clin Oncol 2000; 18: 1831–1836.

    CAS  PubMed  Google Scholar 

  34. Thomas ED, Blume KG, Forman SJ . Hematopoietic Cell Transplantation, 2nd edn. Blackwell Science, Inc: Malden, Massachusetts, USA, 1999.

    Google Scholar 

  35. Mullis KB . The unusual origin of the polymerase chain reaction. Sci Am 1990; 262: 56–61.

    CAS  PubMed  Google Scholar 

  36. Lawler M, McCann SR, Conneally E et al. Chimaerism following allogeneic bone marrow transplantation: detection of residual host cells using the polymerase chain reaction. Br J Haematol 1989; 73: 205–210.

    CAS  PubMed  Google Scholar 

  37. Lawler M, Humphries P, McCann S . 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 

  38. Suttorp M, Schmitz N, Dreger P et al. Monitoring of chimerism after allogeneic bone marrow transplantation with unmanipulated marrow by use of DNA polymorphisms. Leukemia 1993; 7: 679–687.

    CAS  PubMed  Google Scholar 

  39. van Leeuwen JE, van Tol MJ, Bodzinga BG et al. Detection of mixed chimaerism in flow-sorted cell subpopulations by PCR-amplified VNTR markers after allogeneic bone marrow transplantation. Br J Haematol 1991; 79: 218–225.

    CAS  PubMed  Google Scholar 

  40. Bertheas MF, Lafage M, Blaise D et al. Mixed chimerism after allogeneic bone marrow transplantation for leukemias. Bone Marrow Transplant 1990; 6: 61–63.

    PubMed  Google Scholar 

  41. Scharf SJ, Smith AG, Hansen JA et al. Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers. Blood 1995; 85: 1954–1963.

    CAS  PubMed  Google Scholar 

  42. Oberkircher AR, Strout MP, Herzig GP et al. Description of an efficient and highly informative method for the evaluation of hematopoietic chimerism following allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 16: 695–702.

    CAS  PubMed  Google Scholar 

  43. Khan F, Agarwal A, Agarwal S . Significance of chimerism in heamtopoietic stem cell transplantation: new variations on an old theme. Bone Marrow Transplant 2004; 34: 1–12.

    CAS  PubMed  Google Scholar 

  44. Kreyenberg H, Holle W, Mohrle S et al. Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Tuebingen experience. Leukemia 2003; 17: 237–240.

    CAS  PubMed  Google Scholar 

  45. Hancock JP, Goulden NJ, Oakhill A et al. Quantitative analysis of chimerism after allogeneic bone marrow transplantation using immunomagnetic selection and fluorescent microsatellite PCR. Leukemia 2003; 17: 247–251.

    CAS  PubMed  Google Scholar 

  46. Acquaviva C, Duval M, Mirebeau D et al. Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Paris–Robert Debre experience. Leukemia 2003; 17: 241–246.

    CAS  PubMed  Google Scholar 

  47. Chalandon Y, Vischer S, Helg C et al. Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Geneva experience. Leukemia 2003; 17: 228–231.

    CAS  PubMed  Google Scholar 

  48. Lo YM, Tein MS, Lau TK et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998; 62: 768–775.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Fehse B, Chukhlovin A, Kuhlcke K et al. Real-time quantitative Y chromosome-specific PCR (QYCS-PCR) for monitoring hematopoietic chimerism after sex-mismatched allogeneic stem cell transplantation. J Hematother Stem Cell Res 2001; 10: 419–425.

    CAS  PubMed  Google Scholar 

  50. Thiede C, Kellermann T, Schwerdtfeger R et al. Real-time PCR for the SRY-gene allows sensitive and quantitative chimerism analysis after allogeneic blood stem cell transplantation: clinical results in 43 patients. Bone Marrow Transplant 2003; 31: S23.

    Google Scholar 

  51. Bader P, Beck J, Frey A et al. Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplant 1998; 21: 487–495.

    CAS  PubMed  Google Scholar 

  52. Mangioni S, Balduzzi A, Rivolta A et al. Long-term persistence of hemopoietic chimerism following sex-mismatched bone marrow transplantation. Bone Marrow Transplant 1997; 20: 969–973.

    CAS  PubMed  Google Scholar 

  53. Sachidanandam R, Weissman D, Schmidt SC et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409: 928–933.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  55. Maas F, Schaap N, Kolen S et al. Quantification of donor and recipient hemopoietic cells by real-time PCR of single nucleotide polymorphisms. Leukemia 2003; 17: 621–629.

    CAS  PubMed  Google Scholar 

  56. Fredriksson M, Barbany G, Liljedahl U et al. Assessing hematopoietic chimerism after allogeneic stem cell transplantation by multiplexed SNP genotyping using microarrays and quantitative analysis of SNP alleles. Leukemia 2004; 18: 255–266.

    CAS  PubMed  Google Scholar 

  57. Thiede C, Florek M, Bornhauser M et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

    CAS  PubMed  Google Scholar 

  58. de Weger RA, Tilanus MG, Scheidel KC et al. Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats. Br J Haematol 2000; 110: 647–653.

    CAS  PubMed  Google Scholar 

  59. Lion T, Daxberger H, Dubovsky J et al. Analysis of chimerism within specific leukocyte subsets for detection of residual or recurrent leukemia in pediatric patients after allogeneic stem cell transplantation. Leukemia 2001; 15: 307–310.

    CAS  PubMed  Google Scholar 

  60. Ortega M, Escudero T, Caballin MR et al. Follow-up of chimerism in children with hematological diseases after allogeneic hematopoietic progenitor cell transplants. Bone Marrow Transplant 1999; 24: 81–87.

    CAS  PubMed  Google Scholar 

  61. Socie G, Lawler M, Gluckman E et al. Studies on hemopoietic chimerism following allogeneic bone marrow transplantation in the molecular biology era. Leuk Res 1995; 19: 497–504.

    CAS  PubMed  Google Scholar 

  62. McCann SR, Lawler M, Humphries P . Mixed chimaerism. Br J Haematol 1991; 77: 257.

    CAS  PubMed  Google Scholar 

  63. Lawler M, McCann S, Gardiner N et al. Mixed chimerism predicts graft rejection following BMT for severe aplastic anemia. Bone Marrow Transplant 1995; 15: 64 (abstract).

    Google Scholar 

  64. Gyger M, Baron C, Forest L et al. Quantitative assessment of hematopoietic chimerism after allogeneic bone marrow transplantation has predictive value for the occurrence of irreversible graft failure and graft-versus-host disease. Exp Hematol 1998; 26: 426–434.

    CAS  PubMed  Google Scholar 

  65. Dubovsky J, Daxberger H, Fritsch G et al. Kinetics of chimerism during the early post-transplant period in pediatric patients with malignant and non-malignant hematologic disorders: implications for timely detection of engraftment, graft failure and rejection. Leukemia 1999; 13: 2059–2069.

    CAS  PubMed  Google Scholar 

  66. Keil F, Prinz E, Moser K et al. Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival. Transplantation 2003; 76: 230–236.

    CAS  PubMed  Google Scholar 

  67. Childs R, Clave E, Contentin N et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

    CAS  PubMed  Google Scholar 

  68. Nesci S, Manna M, Andreani M et al. Mixed chimerism in thalassemic patients after bone marrow transplantation. Bone Marrow Transplant 1992; 10: 143–146.

    CAS  PubMed  Google Scholar 

  69. Amrolia PJ, Vulliamy T, Vassiliou G et al. Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation. Br J Haematol 2001; 114: 219–225.

    CAS  PubMed  Google Scholar 

  70. Li CK, Chik KW, Tsang KS et al. Mixed chimerism after bone marrow transplantation for thalassemia major. Haematologica 2002; 87: 781–782.

    PubMed  Google Scholar 

  71. Lucarelli G, Andreani M, Angelucci E . The cure of thalassemia by bone marrow transplantation. Blood Rev 2002; 16: 81–85.

    CAS  PubMed  Google Scholar 

  72. Gaziev J, Lucarelli G . Stem cell transplantation for hemoglobinopathies. Curr Opin Pediatr 2003; 15: 24–31.

    PubMed  Google Scholar 

  73. Steinberg MH, Brugnara C . Pathophysiological-based approaches to treatment of sickle cell disease. Annu Rev Med 2003; 54: 89–112.

    CAS  PubMed  Google Scholar 

  74. Steinberg MH . Management of sickle cell disease. N Engl J Med 1999; 340: 1021–1030.

    CAS  PubMed  Google Scholar 

  75. Vermylen C . Hematopoietic stem cell transplantation in sickle cell disease. Blood Rev 2003; 17: 163–166.

    PubMed  Google Scholar 

  76. Walters MC, Storb R, Patience M et al. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood 2000; 95: 1918–1924.

    CAS  PubMed  Google Scholar 

  77. Vermylen C, Cornu G, Ferster A et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22: 1–6.

    CAS  PubMed  Google Scholar 

  78. Walters MC, Patience M, Leisenring W et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 2001; 7: 665–673.

    CAS  PubMed  Google Scholar 

  79. Baron F, Dresse MF, Beguin Y . Donor lymphocyte infusion to eradicate recurrent host hematopoiesis after allogeneic BMT for sickle cell disease. Transfusion 2000; 40: 1071–1073.

    CAS  PubMed  Google Scholar 

  80. Gomez JR, Garcia MJ, Serrano J et al. Chimerism analysis in long-term survivor patients after bone marrow transplantation for severe aplastic anemia. Haematologica 1997; 82: 588–591.

    CAS  PubMed  Google Scholar 

  81. McCann SR, Bacigalupo A, Gluckman E et al. Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. Bone Marrow Transplant 1994; 13: 233–237.

    CAS  PubMed  Google Scholar 

  82. Hill RS, Petersen FB, Storb R et al. Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease. Blood 1986; 67: 811–816.

    CAS  PubMed  Google Scholar 

  83. Hoelle W, Beck JF, Dueckers G et al. Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia. Bone Marrow Transplant 2004; 33: 219–223.

    CAS  PubMed  Google Scholar 

  84. Woodard P, Cunningham JM, Benaim E et al. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant 2004; 33: 411–418.

    CAS  PubMed  Google Scholar 

  85. Antin JH, Childs R, Filipovich AH et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2001; 7: 473–485.

    CAS  PubMed  Google Scholar 

  86. Hoelle W, Kreyenberg H, Lang P et al. Hematopoietic chimerism and donor lymphocyte infusion after allogeneic SCT in children with non malignant diseases: is there an option to improve outcome? Klin Paediatr 2004; in press.

  87. Roux E, Helg C, Chapuis B et al. Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction. Blood 1992; 79: 2775–2783.

    CAS  PubMed  Google Scholar 

  88. 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 hematologic lineages before and after relapse. Blood 1993; 81: 243–248.

    CAS  PubMed  Google Scholar 

  89. Mackinnon S, Barnett L, Heller G et al. Minimal residual disease is more common in patients who have mixed T-cell chimerism after bone marrow transplantation for chronic myelogenous leukemia. Blood 1994; 83: 3409–3416.

    CAS  PubMed  Google Scholar 

  90. Gardiner N, Lawler M, O'Riordan J et al. Persistent donor chimaerism is consistent with disease-free survival following BMT for chronic myeloid leukaemia. Bone Marrow Transplant 1997; 20: 235–241.

    CAS  PubMed  Google Scholar 

  91. Roux E, Helg C, Chapius B et al. Mixed chimerism after bone marrow transplantation and the risk of relapse. Blood 1994; 84: 4385–4386.

    CAS  PubMed  Google Scholar 

  92. van Leeuwen JE, van Tol MJ, Joosten AM et al. Mixed T-lymphoid chimerism after allogeneic bone marrow transplantation for hematologic malignancies of children is not correlated with relapse. Blood 1993; 82: 1921–1928.

    CAS  PubMed  Google Scholar 

  93. Roy DC, Tantravahi R, Murray C et al. Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium. Blood 1990; 75: 296–304.

    CAS  PubMed  Google Scholar 

  94. Bertheas MF, Maraninchi D, Lafage M et al. Partial chimerism after T-cell-depleted allogeneic bone marrow transplantation in leukemic HLA-matched patients: a cytogenetic documentation. Blood 1988; 72: 89–93.

    CAS  PubMed  Google Scholar 

  95. Molloy K, Goulden N, Lawler M et al. Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors. Blood 1996; 87: 3027–3031.

    CAS  PubMed  Google Scholar 

  96. Formankova R, Honzatkova L, Sieglova Z et al. Detailed monitoring of hematopoietic chimerism in a child treated by adoptive immunotherapy for high risk of relapse after BMT for acute myeloid leukemia. Bone Marrow Transplant 2000; 25: 453–456.

    CAS  PubMed  Google Scholar 

  97. Formankova R, Sedlacek P, Krskova L et al. Chimerism-directed adoptive immunotherapy in prevention and treatment of post-transplant relapse of leukemia in childhood. Haematologica 2003; 88: 117–118.

    PubMed  Google Scholar 

  98. Fernandez-Aviles F, Urbano-Ispizua A, Aymerich M et al. Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood. Leukemia 2003; 17: 613–620.

    CAS  PubMed  Google Scholar 

  99. Gorczynska E, Turkiewicz D, Toporski J et al. Prompt initiation of immunotherapy in children with an increasing number of autologous cells after allogeneic HCT can induce complete donor-type chimerism: a report of 14 children. Bone Marrow Transplant 2004; 33: 211–217.

    CAS  PubMed  Google Scholar 

  100. Schaap N, Schattenberg A, Mensink E et al. Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. Leukemia 2002; 16: 13–21.

    CAS  PubMed  Google Scholar 

  101. Choi SJ, Lee KH, Lee JH et al. Prognostic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study. Bone Marrow Transplant 2000; 26: 327–332.

    CAS  PubMed  Google Scholar 

  102. Guimond M, Busque L, Baron C et al. Relapse after bone marrow transplantation: evidence for distinct immunological mechanisms between adult and paediatric populations. Br J Haematol 2000; 109: 130–137.

    CAS  PubMed  Google Scholar 

  103. Bader P, Stoll K, Huber S et al. Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse. Br J Haematol 2000; 108: 761–768.

    CAS  PubMed  Google Scholar 

  104. Barrios M, Jimenez-Velasco A, Roman-Gomez J et al. Chimerism status is a useful predictor of relapse after allogeneic stem cell transplantation for acute leukemia. Haematologica 2003; 88: 801–810.

    PubMed  Google Scholar 

  105. Formankova R, Sedlacek P, Krskova L et al. Chimerism-directed adoptive immunotherapy in prevention and treatment of post-transplant relapse of leukemia in childhood. Haematologica 2003; 88: 117–118.

    PubMed  Google Scholar 

  106. Prinz E, Keil F, Kalhs P et al. Successful immunotherapy in early relapse of acute myeloid leukemia after nonmyeloablative allogeneic stem cell transplantation. Ann Hematol 2003; 82: 295–298.

    CAS  PubMed  Google Scholar 

  107. Bader P, Kreyenberg H, Hoelle W et al. Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. Bone Marrow Transplant 2004; 33: 815–821.

    CAS  PubMed  Google Scholar 

  108. Beck JF, Klingebiel T, Kreyenberg H et al. Relapse of childhood ALL, AML and MDS after allogeneic stem cell transplantation can be prevented by donor lymphocyte infusion in a critical stage of increasing mixed chimerism. Klin Paediatr 2002; 214: 201–205.

    CAS  Google Scholar 

  109. Bader P, Kreyenberg H, Hoelle W et al. Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: possible role for pre-emptive immunotherapy? J Clin Oncol 2004; 22: 1696–1706.

    PubMed  Google Scholar 

  110. Knechtli CJ, Goulden NJ, Hancock JP et al. Minimal residual disease status as a predictor of relapse after allogeneic bone marrow transplantation for children with acute lymphoblastic leukaemia. Br J Haematol 1998; 102: 860–871.

    CAS  PubMed  Google Scholar 

  111. Bader P, Hancock J, Kreyenberg H et al. Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL. Leukemia 2002; 16: 1668–1672.

    CAS  PubMed  Google Scholar 

  112. van der Velden VH, Joosten SA, Willemse MJ et al. Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia. Leukemia 2001; 15: 1485–1487.

    CAS  PubMed  Google Scholar 

  113. van Dongen JJ, Langerak AW, Bruggemann M et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17: 2257–2317.

    CAS  PubMed  Google Scholar 

  114. Gabert J, Beillard E, van der Velden V et al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. Leukemia 2003; 17: 2318–2357.

    CAS  PubMed  Google Scholar 

  115. van der Velden VH, Hochhaus A, Cazzaniga G et al. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia 2003; 17: 1013–1034.

    CAS  PubMed  Google Scholar 

  116. Thiede C, Bornhauser M, Oelschlagel U et al. Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR amplification of short tandem repeat-markers. Leukemia 2001; 15: 293–302.

    CAS  PubMed  Google Scholar 

  117. Thiede C, Lutterbeck K, Oelschlagel U et al. Detection of relapse by sequential monitoring of chimerism in circulating CD34+ cells. Ann Hematol 2002; 81: S27–S28.

    PubMed  Google Scholar 

  118. Thiede C . Diagnostic chimerism analysis after allogeneic stem cell transplantation. Am J Pharmacogenomics 2004; 4: 177–187.

    CAS  PubMed  Google Scholar 

  119. Mattsson J, Uzunel M, Tammik L et al. 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.

    CAS  PubMed  Google Scholar 

  120. Winiarski J, Gustafsson A, Wester D et al Follow-up of chimerism, including T- and B-lymphocytes and granulocytes in children more than one year after allogeneic bone marrow transplantation. Pediatr Transplant 2000; 4: 132–139.

    CAS  PubMed  Google Scholar 

  121. Winiarski J, Mattsson J, Gustafsson A et al. Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation. Pediatr Transplant 1998; 2: 150–156.

    CAS  PubMed  Google Scholar 

  122. Zetterquist H, Mattsson J, Uzunel M et al. Mixed chimerism in the B cell lineage is a rapid and sensitive indicator of minimal residual disease in bone marrow transplant recipients with pre-B cell acute lymphoblastic leukemia. Bone Marrow Transplant 2000; 25: 843–851.

    CAS  PubMed  Google Scholar 

  123. Lamb Jr LS, Robbins NF, Abhyankar S et al. Flow cytometric cell sorting combined with molecular chimerism analysis to detect minimal recurrent leukemia: good news and bad news. Bone Marrow Transplant 1997; 19: 1157–1161.

    PubMed  Google Scholar 

  124. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    CAS  PubMed  Google Scholar 

  125. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  126. Feinstein LC, Sandmaier BM, Hegenbart U et al. Non-myeloablative allografting from human leucocyte antigen-identical sibling donors for treatment of acute myeloid leukaemia in first complete remission. Br J Haematol 2003; 120: 281–288.

    PubMed  Google Scholar 

  127. Niederwieser D, Maris M, Shizuru JA et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

    CAS  PubMed  Google Scholar 

  128. Georges GE, Storb R, Thompson JD et al. Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation. Blood 2000; 95: 3262–3269.

    CAS  PubMed  Google Scholar 

  129. Spitzer TR . Nonmyeloablative allogeneic stem cell transplant strategies and the role of mixed chimerism. Oncologist 2000; 5: 215–223.

    CAS  PubMed  Google Scholar 

  130. Spitzer TR, McAfee S, Sackstein R et al. Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol Blood Marrow Transplant 2000; 6: 309–320.

    CAS  PubMed  Google Scholar 

  131. Orsini E, Alyea EP, Chillemi A et al. Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma. Biol Blood Marrow Transplant 2000; 6: 375–386.

    CAS  PubMed  Google Scholar 

  132. Baron F, Baker JE, Storb R et al. Kinetics of engraftment in patients with hematological malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004; pub. ahead.

  133. Djulbegovic B, Seidenfeld J, Bonnell C et al. Nonmyeloablative allogeneic stem-cell transplantation for hematologic malignancies: a systematic review. Cancer Control 2003; 10: 17–41.

    PubMed  Google Scholar 

  134. Matthes-Martin S, Lion T, Haas OA et al. Lineage-specific chimaerism after stem cell transplantation in children following reduced intensity conditioning: potential predictive value of NK cell chimaerism for late graft rejection. Leukemia 2003; 17: 1934–1942.

    CAS  PubMed  Google Scholar 

  135. Bornhauser M, Thiede C, Platzbecker U et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res 2001; 7: 2254–2262.

    CAS  PubMed  Google Scholar 

  136. Girgis M, Hallemeier C, Blum W et al. Chimerism and clinical outcomes of 110 unrelated donor bone marrow transplant recipients conditioned with low dose (550 cGy), single exposure total body irradiation and cyclophosphamide. Blood 2004; pub. ahead.

Download references

Acknowledgements

This work was supported by the ‘Deutsche Krebshilfe’ (grants 70-2178 and 50-2737), Bonn, Germany.

Author information

Authors and Affiliations

  1. University Children's Hospital, Tübingen, Germany

    P Bader, D Niethammer, A Willasch & H Kreyenberg

  2. University Children's Hospital, Frankfurt, Germany

    T Klingebiel

Authors
  1. P Bader
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Niethammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Willasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Kreyenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Klingebiel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Bader.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bader, P., Niethammer, D., Willasch, A. et al. How and when should we monitor chimerism after allogeneic stem cell transplantation?. Bone Marrow Transplant 35, 107–119 (2005). https://doi.org/10.1038/sj.bmt.1704715

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704715

Keywords

This article is cited by

Search

Advanced search

Quick links