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:

Chimerism

Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning

Bone Marrow Transplantation volume 31, pages 387–392 (2003)Cite this article

Summary:

We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.

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

Similar content being viewed by others

References

  1. Giralt S, Estey E, Albitar M et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy. Harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  2. Khouri IF, Keating M, Korbling M et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  PubMed  Google Scholar 

  3. 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 hematological diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  4. 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 

  5. Carella AM, Champlin R, Slavin S et al. Mini-allografts: ongoing trials in humans (editorial). Bone Marrow Transplant 2000; 25: 345–350.

    Article  CAS  PubMed  Google Scholar 

  6. Carella AM, Giralt S, Slavin S . Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia. Haematologica 2000; 85: 304–313.

    CAS  PubMed  Google Scholar 

  7. Martino R, Caballero MD, Canals C et al for the alloPBSCT subcommittee of the Spanish Group for Hematopoietic Transplantation (GETH) and theGroup GEL-TAMO. Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicenter study. Br J Haematol 2001; 115: 653–659.

    Article  CAS  PubMed  Google Scholar 

  8. Ferrara JLM, Deeg HJ . Graft-versus-host disease. N Engl J Med 1991; 324: 667–674.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Giralt S, Thall PF, Khouri I et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

    Article  CAS  PubMed  Google Scholar 

  11. Mattsson J, Uzunel M, Brune M et al. Mixed chimerism is common at the time of acute graft-versus-host disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol 2001; 115: 935–944.

    Article  CAS  PubMed  Google Scholar 

  12. Kottaridis PD, Milligan DW, Chopra R et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    CAS  PubMed  Google Scholar 

  13. 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. Biol Blood Marrow Transplant 2001; 7: 473–485.

    Article  CAS  PubMed  Google Scholar 

  14. Mattsson J, Uzunel M, Remberger M et al. T-cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Transplantation 2001; 71: 433–439.

    Article  CAS  PubMed  Google Scholar 

  15. 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-vs-host disease. Exp Hematol 1998; 26: 426–434.

    CAS  PubMed  Google Scholar 

  16. Molina A, McSweeney P, Maloney DG et al. Degree of early donor T-cell chimerism predicts GVHD and graft rejection in patients with nonmyeloablative hematopoietic stem cell allografts. Blood 1999; 94: 394a.

    Google Scholar 

  17. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  18. Weiden PL, Flournoy N, Thomas ED et al. Antileukemic effect of graft- versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    Article  CAS  PubMed  Google Scholar 

  19. Champlin RE, Schmitz N, Horowitz MM et al. Blood stem cells compared with bone marrow transplantation as a source of hematopoietic cells for allogeneic transplantation. Blood 2000; 95, 3702–3709.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    D Valcárcel, R Martino, C Canals & J Sierra

  2. Department of Hematology, Hospital Clínico Universitario de Salamanca, Spain

    D Caballero, M V Mateos, J A Pérez-Simón, M Gonzalez & J F San Miguel

  3. Department of Hematology, Hospital Clinic i Provicial de Barcelona, Spain

    F Fernández

  4. Department of Hematology, Hospital de Son Dureta de Mallorca, Spain

    J Bargay

  5. Blood Bank, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    E Muñiz-Díaz

Authors
  1. D Valcárcel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Caballero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M V Mateos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J A Pérez-Simón
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Canals
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Bargay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Muñiz-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J F San Miguel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Sierra
    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

Valcárcel, D., Martino, R., Caballero, D. et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 31, 387–392 (2003). https://doi.org/10.1038/sj.bmt.1703846

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703846

Keywords

This article is cited by

Search

Advanced search

Quick links