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 Manuscript
  • Published:

BMT

Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival

Abstract

We retrospectively analyzed the prognostic significance of mixed chimerism and associated clinical parameters in 80 patients following unmanipulated allogenic stem cell transplantation. Chimerism studies were performed on marrow aspirates using fluorescent in situ hybridization and variable number tandem repeats techniques at day +30, day +90 and +12 months. The median overall survival (OS) was 24 months (range, 1–56 months). Mixed chimerism was found in 23, 28 and 14% of patients at day +30 (1 month), +90 (3 months), and +12 months, respectively. Day +30 chimerism studies failed to provide any prognostic information. Day +90 mixed chimeras (MC) had significantly higher relapse rates compared to day +90 complete chimeras (CC) at 6 months (P=0.03) and 18 months when compared to MC (P=0.03) following transplant. The median OS in day +90 MC and day+90 CC were, respectively (95% CI, 2–35 months), compared to 47 months (95% CI, 20–74 months) (P=0.02). In conclusion, chimerism studies on day +30 could be reserved for patients who fail to demonstrate engraftment. Day +90 MC had higher relapse rates and lower OS, and therefore may be considered for novel therapies and future studies.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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. Ugozzoli L, Yam P, Petz LD, Ferrara GB, Champlin RE, Forman SJ et al. Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation. Blood 1991; 77: 1607–1615.

    CAS  PubMed  Google Scholar 

  2. van Dekken H, Hangenbeek A, Bauman JG . Detection of host cells following sex-mismatched bone marrow transplantation by fluorescent in situ hybridization with a Y-chromosome specific probe. Leukemia 1989; 3: 724–728.

    CAS  PubMed  Google Scholar 

  3. Roth MS, Antin JH, Bingham EL, Ginsburg D . Use of polymerase chain reaction detected sequence polymorphisms to document engraftment following allogenic bone marrow transplantation. Transplantation 1990; 49: 714–720.

    Article  CAS  PubMed  Google Scholar 

  4. Chalmers EA, Sproul AM, Mills KI, Gibson BE, Burnett AK . Use of polymerase chain reaction to monitor engraftment following allogenic bone marrow transplantation. Bone Marrow Transplant 1990; 6: 399–403.

    CAS  PubMed  Google Scholar 

  5. Browne PV, Lawler M, O'Riordan J, Humphries P, McCann SR . Early detection of leukemic relapse after bone marrow transplantation using the polymerase chain reaction. Bone Marrow Transplant 1991; 7: 167–169.

    CAS  PubMed  Google Scholar 

  6. 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 

  7. Ortega M, Escudero T, Caballin MR, Olive T, Ortega JJ, Coll MD . Follow up of chimerism in children with hematological diseases after allogenic hematopoietic progenitor cell transplants. Bone Marrow Transplant 1999; 24: 81–87.

    Article  CAS  PubMed  Google Scholar 

  8. van Leeuwen JE, van Tol MJ, Joosten AM, Wijnen JT, Verweij PJ, Khan PM et al. Persistence of host-type hematopoiesis after allogenic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but is not associated with an increased risk of relapse. Blood 1994; 83: 3059–3067.

    CAS  PubMed  Google Scholar 

  9. Ugozzoli L, Yam P, Petz LD, Ferrara GB, Champlin RE, Forman SJ et al. Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation. Blood 1991; 77: 1607–1615.

    CAS  PubMed  Google Scholar 

  10. Boerwinkle E, Xiong W, fourest E, Chan L . Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: Application to the apolipoprotein B 3′ hypervariable region. Genetics 1989; 86: 212–216.

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  12. Petz LD, Yam P, Wallace RB, Stock AD, de Lange G, Knowlton RG et al. Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies. Blood 1987; 70: 1331–1337.

    CAS  PubMed  Google Scholar 

  13. Bader P, Holle W, Klingebiel T, Handgretinger R, Benda N, Schlegel PG et al. Mixed hematopoietic chimerism after allogenic bone marrow transplantation: the impact of quantitative PCR analysis for prediction of relapse and graft rejection in children. Bone Marrow Transplant 1999; 19: 697–702.

    Article  Google Scholar 

  14. Bertheas MF, Lafage M, Levy P, Blaise D, Stoppa AM, Viens P et al. Influence of mixed chimerism on the results of allogenic bone marrow transplantation for leukemia. Blood 1991; 78: 3103–3106.

    CAS  PubMed  Google Scholar 

  15. Offit K, Burns JP, Cunningham I, Jhanwar SC, Black P, Kernan NA 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 

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

    CAS  PubMed  Google Scholar 

  17. Bretagne S, Vidaud M, Kuentz M, Cordonnier C, Henni T, Vinci G et al. Mixed blood chimerism in T cell depleted bone marrow transplant recipients: evaluation using DNA polymorphisms. Blood 1987; 70: 1692–1695.

    CAS  PubMed  Google Scholar 

  18. McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications. Biol Blood Marrow Transplant 1999; 5: 192–203.

    Article  CAS  PubMed  Google Scholar 

  19. Schattenberg A, Bar B, Smeets D, Geurts van Kessel A, De Witte T . Comparision of chimerism of red cells with that of granulocytes, T-lymphocytes and bone marrow cells in recipients of bone marrow grafts depleted of lymphocytes using counter flow centrifugation. Leukemia Lymphoma 1991; 5: 171–177.

    Article  CAS  PubMed  Google Scholar 

  20. Suttorp M, Schmitz N, Dreger P, Schaub J, Loffler H . Monitoring of chimerism after allogenic bone marrow transplantation with unmanipulated marrow by use of DNA polymorphisms. Leukemia 1993; 7: 679–687.

    CAS  PubMed  Google Scholar 

  21. Champlin R, Mc Glave P . Allogenic bone marrow transplantation for chronic myelogenous leukemia. In: Forman S, Blume K, Thomas E (eds) Bone Marrow Transplantation. Boston, MA: Blackwell Scientific, 1994, p 595.

    Google Scholar 

  22. Long G, Blume K . Allogenic bone marrow transplantation for acute myeloid leukemia. In: Forman S, Blume K, Thomas E (eds) Bone Marrow Transplantation. Boston, MA: Blackwell Scienticfic, 1994, p 607.

    Google Scholar 

  23. Chao N, Forman S . Allogenic bone marrow transplantation for acute lymphoblastic leukemia. In: Forman S, Blume K, Thomas E (eds) Bone Marrow Transplantation. Boston, MA: Blackwell Scientific, 1994, p 618.

    Google Scholar 

  24. Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: Increased risk of relapse associated with T-cell depletion. Ann Intern Med 1988; 108: 806–814.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Molloy K, Goulden N, Lawler M, Cornish J, Oakhill A, Pamphilon D 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 

  27. Roman J, Martin C, Torres A, Garcia A, Andres P, Garcia MJ et al. Importance of mixed chimerism to predict relapse in persistently bcr/abl positive long term survivors after allogenic bone marrow transplantation for chronic myeloid leukemia. Leukemia Lymphoma 1998; 28: 541–550.

    Article  CAS  PubMed  Google Scholar 

  28. Radich JP, Gehly G, Gooley T, Bryant E, Clift RA, Collins S et al. Polymerasechain reaction detection of BCR-ABL fusion transcript after allogenic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood 1995; 85: 2632–2638.

    CAS  PubMed  Google Scholar 

  29. Socie G, Lawler M, Gluckman E, McCann SR, Brison O . Studies on hematopoietic chimerism following allogenic bone marrow transplantation in the molecular biology era. Leukemia Res 1995; 19: 497–504.

    Article  CAS  Google Scholar 

  30. Dubovsky J, Daxberger H, Fritsch G, Printz D, Peters C, Matthes S 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: 2060–2069.

    Article  CAS  Google Scholar 

  31. Frassoni F, Strada P, Sessarego M, Miceli S, Corvo R, Scarpati D et al. Mixed chimerism after allogenic marrow transplantation for leukemia: correlation with dose of total body irradiation and graft-versus-host disease. Bone Marrow Transplant 1990; 5: 235–240.

    CAS  PubMed  Google Scholar 

  32. Chalmers EA, Sproul AM, Mills KI, Stewart J, McNee S, Jones R et al. Effect of radiation dose on the development of mixed haemopoietic chimerism following T-cell depleted allogenic bone marrow transplantation. Bone Marrow Transplant 1992; 10: 425–430.

    CAS  PubMed  Google Scholar 

  33. Mackinnon S, Barnett L, Bourhis JH, Black P, Heller G, O'Reilly RJ . Myeloid and lymphoid chimerism after T-cell depleted bone marrow transplantation: evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA. Blood 1992; 80: 3235–3241.

    CAS  PubMed  Google Scholar 

  34. Bar BM, Schattenberg A, De Man AJ, Hoogenhout MJ, Boezeman J, de Witte T . Influence of the conditioning regimen on erythrocyte chimerism, graft-versus-host disease and relapse after allogenic transplantation with lymphocyte depleted marrow. Bone Marrow Transplant 1992; 10: 45–52.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ronald L Thomas for statistical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E Peres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamba, R., Abella, E., Kukuruga, D. et al. Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival. Leukemia 18, 1681–1686 (2004). https://doi.org/10.1038/sj.leu.2403468

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403468

Keywords

This article is cited by

Search

Quick links