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.

  • Debate Round Table
  • Published:

Chimerism testing and detection of minimal residual disease after allogeneic hematopoietic transplantation using the bioView (Duet™) combined morphological and cytogenetical analysis

Leukemia volume 16, pages 1413–1418 (2002)Cite this article

Abstract

Recurrent disease remains a major obstacle to cure after allogeneic transplantation. Various methods have been developed to detect minimal residual disease (MRD) after transplantation to identify patients at risk for relapse. Chimerism tests differentiate recipient and donor cells and are used to identify MRD when there are no other disease-specific markers. The detection of MRD does not always correlate with relapse risk. Chimerism testing may also identify normal hematopoietic cells or other cells not contributing to relapse. In this study we report our initial experience with a novel system that provides combined morphological and cytogenetical analysis on the same cells. This system allows rapid automatic scanning of a large number of cells, thus increasing the sensitivity of detection of small recipient population. The clinical significance of MRD detection is improved by identifying the morphology of recipient cells. Identification of recipient characteristics within blasts predicts overt relapse in leukemia patients and precedes it by a few weeks to months. Identification within mature hematopoietic cells may not be closely associated with relapse. The system also allows chimerism testing after sex-mismatched transplants, within cellular subsets, with no need for sorting of cells. The system merits further study in larger scale trials.

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. Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Nieman PE, Lender KG, Glucksberg H, Buckner CD . Bone marrow transplantation N Engl J Med 1975 292: 832–843

    Article  CAS  PubMed  Google Scholar 

  2. Shimoni A, Nagler A . Non-myeloablative stem-cell transplantation (NST): chimerism testing as guidance for immune-therapeutic manipulations Leukemia 2001 15: 1967–1975

    Article  CAS  PubMed  Google Scholar 

  3. Bader P, Klingebiel T, Schaudt A, Theurer-Mainka U, Handgretinger R, Lang P, Niethammer D, Beck JF . Prevention of relapse in pediatric patients with acute leukemias and MDS after allogeneic SCT by early immunotherapy initiated on the basis of increasing mixed chimerism: a single center experience of 12 children Leukemia 1999 13: 2079–2086

    Article  CAS  PubMed  Google Scholar 

  4. Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, Goodman SA, Wolff SN, Hu W, Verfaillie C, List A, Dalton W, Ognoskie N, Chetrit A, Antin JH, Nemunaitis J . Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation J Clin Oncol 1997 15: 433–444

    Article  PubMed  Google Scholar 

  5. Toren A, Rechavi G, Nagler A . Minimal residual disease post bone-marrow transplantation for hemato-oncological diseases Stem Cells 1996 14: 300–311

    Article  CAS  PubMed  Google Scholar 

  6. Lion T, Muller-Berat N . Chimerism testing after allogeneic stem cell transplantation: importance of timing and optimal technique for chimerism testing in different clinical–biological situations Leukemia 1999 13: 2059

    Article  CAS  PubMed  Google Scholar 

  7. Lion T . Chimerism testing after allogeneic stem cell transplantation: importance of timing and optimal technique for chimerism testing in different clinical–biological situations Leukemia 2001 15: 292

    Article  PubMed  Google Scholar 

  8. Esa A, Trakhtenbrot L, Hausmann M, Rauch J, Brok-Simoni F, Rechavi G, Ben-Bassat I, Cremer C . Fast-FISH detection and semi-automatic image analysis of numerical chromosome aberration in hematological malignancies Anal Cell Pathol 1998 16: 211–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Durnam DM, Anders KR, Fisher L, O'Quigley J, Bryant EM, Thomas ED . Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay Blood 1989 74: 2220–2226

    CAS  PubMed  Google Scholar 

  10. Thiede C, Bornhauser M, Oelschlagel U, Brendel C, Leo R, Daxberger H, Mohr B, Florek M, Kroschinsky F, Geissler G, Naumann R, Ritter M, Prange-Krex G, Lion T, Neubauer A, Ehninger G . 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

    Article  CAS  PubMed  Google Scholar 

  11. Dubovski J, Daxberger H, Prinz D, Peters C, Matthes S, Gadner H, Lion T . 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  Google Scholar 

  12. Nagler A, Slavin S, Yarkoni S, Fejgin M, Amiel A . Detection of minimal residual disease after sex-mismatch bone marrow transplantation in chronic myelogenous leukemia by fluorescence in situ hybridization Cancer Genet Cytogenet 1994 73: 130–133

    Article  CAS  PubMed  Google Scholar 

  13. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV . The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease Blood 1998 92: 3362–3367

    CAS  PubMed  Google Scholar 

  14. Yarkoni S, Lishner M, Tangi H, Nagler A, Lorberboum-Galski H . B-cell non-Hodgkin's lymphoma: evidence for the t(14;18) translocation in all hematopoietic cell lineages J Natl Cancer Inst 1996 88: 973–979

    Article  CAS  PubMed  Google Scholar 

  15. Jurlander J, Caligiuri MA, Ruutu T, Baer MR, Strout MP, Oberkircher AR, Hoffmann L, Ball ED, Frei-Lahr DA, Christiansen NP, Block AM, Knuutila S, Herzig GP, Bloomfield CD . Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia Blood 1996 88: 2183–2191

    CAS  PubMed  Google Scholar 

  16. Perego RA, Marenco P, Bianchi C, Cairoli R, Urbano M, Nosari AM, Muti G, Morra E, Del Monte U . PML/RAR alpha transcripts monitored by polymerase chain reaction in acute promyelocytic leukemia during complete remission, relapse and after bone marrow transplantation Leukemia 1996 10: 207–212

    CAS  PubMed  Google Scholar 

  17. Greaves M . Silence of the leukemic clone N Engl J Med 1997 336: 367–369

    Article  CAS  PubMed  Google Scholar 

  18. Cohen N, Novikov I, Hardan I, Esa A, Brok-Simoni F, Amariglio N, Rechavi G, Ben-Bassat I, Trakhtenbrot L . Standardization criteria for the detection of BCR/ABL fusion in interphase nuclei of chronic myelogenous leukemia patients by fluorescence in situ hybridization Cancer Genet Cytogenet 2000 123: 102–108

    Article  CAS  PubMed  Google Scholar 

  19. Childs R, Clave E, Contentin N, Jayasekara D, Hensel N, Leitman S, Read EJ, Carter C, Bahceci E, Young NS, Barrett AJ . Engraftment kinetics after nonmyeloablative allogeneic peripheral blood transplantation: full donor T-cell chimerism precedes alloimmune responses Blood 1999 94: 3234–3241

    CAS  PubMed  Google Scholar 

  20. Lion T, Daxberger H, Dubovsky J, Filipcik P, Fritsch G, Printz D, Peters C, Matthes-Martin S, Lawitschka A, Gadner H . 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

    Article  CAS  PubMed  Google Scholar 

  21. Nagler A, Ilan Y, Amiel A, Eid A, Tur-Kaspa R . Systemic chimerism in sex-mismatched liver transplant recipients detected by fluorescence in situ hybridization Transplantation 1994 57: 1458–1461

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    A Shimoni, A Nagler, A Avigdor, I Hardan & M Yeshurun

  2. Department of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    C Kaplinsky, N Amariglio, F Brok-Simoni, G Rechavi & L Trakhtenbrot

  3. BioView Ltd, Nes-Ziona, Israel

    M Reichart, M Daniely & Y Zilberstein

Authors
  1. A Shimoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Nagler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Kaplinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Reichart
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Avigdor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I Hardan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Yeshurun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Daniely
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y Zilberstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N Amariglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F Brok-Simoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. G Rechavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. L Trakhtenbrot
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimoni, A., Nagler, A., Kaplinsky, C. et al. Chimerism testing and detection of minimal residual disease after allogeneic hematopoietic transplantation using the bioView (Duet™) combined morphological and cytogenetical analysis. Leukemia 16, 1413–1418 (2002). https://doi.org/10.1038/sj.leu.2402581

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402581

Keywords

This article is cited by

Search

Advanced search

Quick links