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:

Graft-Versus-Tumor Effects

Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia—Update study

Bone Marrow Transplantation volume 44, pages 799–804 (2009)Cite this article

Abstract

We earlier published data on 136 children who received hematopoietic SCT (HSCT) for ALL, and showed that early lymphocyte recovery is a powerful indicator for survival by GVL effect without increase in GVHD. To answer the question whether this is true for AML, we extended our cohort to 207 consecutive children with acute leukemia by adding 71 children with AML who received 75 HSCT's between 1994 and 2005. For the AML cohort, all patients at time of HSCT were in complete morphological remission (CR) except for one patient in CR1, who had 8% blasts in the BM before HSCT. All patients received myeloablative regimens. Stem cell sources were: matched sibling donor in 40 patients, mismatched related donor in eight patients, matched unrelated donor in 25 children and two children received cord progenitor stem cells. ALL results were published with significant P-values. In AML, absolute lymphocyte count <0.3 × 109/l or >0.3 × 109/l on days 21 and 30 were not predictive of relapse with a hazard ratio at day 21=0.88; P=0.8, and hazard ratio at day 30=0.5; P=0.2.

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. Barrett AJ, Horowitz MM, Pollock BH, Zhang MJ, Bortin MM, Buchanan GR et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 1994; 331: 1253–1258.

    Article  CAS  PubMed  Google Scholar 

  2. Mehta J, Powles R, Treleaven J, Horton C, Meller S, Pinkerton CR et al. Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy. Bone Marrow Transplant 1997; 19: 709–719.

    Article  CAS  PubMed  Google Scholar 

  3. Gibson BE, Wheatley K, Hann IM, Stevens RF, Webb D, Hills RK et al. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia 2005; 19: 2130–2138.

    Article  CAS  PubMed  Google Scholar 

  4. Aladjidi N, Auvrignon A, Leblanc T, Perel Y, Bénard A, Bordigoni P et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. J Clin Oncol 2003; 21: 4377–4385.

    Article  CAS  PubMed  Google Scholar 

  5. Dopfer R, Henze G, Bender-Gotze C, Ebell W, Ehninger G, Friedrich W et al. Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study. Blood 1991; 78: 2780–2784.

    CAS  PubMed  Google Scholar 

  6. Uderzo C, Valsecchi MG, Bacigalupo A, Meloni G, Messina C, Polchi P et al. Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association. J Clin Oncol 1995; 13: 352–358.

    Article  CAS  PubMed  Google Scholar 

  7. Jiang YZ, Kanfer EJ, Macdonald D, Cullis JO, Goldman JM, Barrett AJ . Graft-versus-leukaemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukaemia cells. Bone Marrow Transplant 1991; 8: 253–258.

    CAS  PubMed  Google Scholar 

  8. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  9. Ishaqi MK, Afzal S, Dupuis A, Doyle J, Gassas A . Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant 2008; 41: 245–252.

    Article  CAS  PubMed  Google Scholar 

  10. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  11. Collins Jr RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. 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 

  12. Glucksberg H, Storb R, Fefer A Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  13. Atkinson K, Horowitz MM, Gale RP, Lee MB, Rimm AA, Bortin MM . Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant 1989; 4: 247–254.

    CAS  PubMed  Google Scholar 

  14. Kumar S, Chen MG, Gastineau DA, Gertz MA, Inwards DJ, Lacy MQ et al. Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplant 2001; 28: 951–956.

    Article  CAS  PubMed  Google Scholar 

  15. Powles R, Singhal S, Treleaven J, Kulkarni S, Horton C, Mehta J . Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood 1998; 91: 3481–3486.

    CAS  PubMed  Google Scholar 

  16. Gassas A, Sung L, Saunders EF, Doyle J . Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia:significantly lower relapse rate in unrelated transplantations. Bone Marrow Transplant 2007; 40: 951–955.

    Article  CAS  PubMed  Google Scholar 

  17. Triplett B, Handgretinger R, Pui CH, Leung W . KIR-incompatible hematopoietic-cell transplantation for poor prognosis infant acute lymphoblastic leukemia. Blood 2006; 107: 1238–1239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are indebted to the patient's families, nursing and medical staff of the BMT unit and our referral centers across Ontario for the provision of excellent patient care and continuing support.

Author information

Authors and Affiliations

  1. Division of Haematology/Oncology/BMT, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    S Afzal, M K Ishaqi, J Doyle & A Gassas

  2. Division of Clinical Research Support Unit, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    A Dupuis

Authors
  1. S Afzal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M K Ishaqi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Dupuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Doyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Gassas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Gassas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Afzal, S., Ishaqi, M., Dupuis, A. et al. Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia—Update study. Bone Marrow Transplant 44, 799–804 (2009). https://doi.org/10.1038/bmt.2009.91

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.91

Keywords

This article is cited by

Search

Advanced search

Quick links