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:

Relapse of Leukaemia

Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course

Bone Marrow Transplantation volume 32, pages 835–842 (2003)Cite this article

Summary:

A total of 118 consecutive adult patients with acute leukemia (78 AML, 36 ALL, and four acute mixed lineage leukemia) underwent allogeneic hematopoietic cell transplantation (HCT) after conditioning with BuCy (n=113) or a nonmyeloablative regimen of busulfan-fludarabine (n=5). After a median follow-up of 35.8 months (range, 6.4–91.0), 34 patients experienced at least one episode of leukemia relapse. Of 34 initial episodes, 14 (41%) occurred in extramedullary sites, with (n=8) or without (n=6) concomitant bone marrow involvement. The median time to relapse in the extramedullary sites was longer than that of relapse in bone marrow only (13.5 vs 6.1 months, P=0.046). Acute leukemia subtype and disease status at HCT showed an independent predictive value for overall relapse, as well as for extramedullary relapse with or without bone marrow involvement (Philadelphia chromosome positive acute leukemia vs low-risk AML, relative risk 22.68 (95% CI, 2.18–235.64); other than first CR vs first CR, relative risk 5.61 (95% CI, 1.80-17.51)), but not for bone marrow relapse. Our study suggests that there may be different pathogenetic mechanisms for bone marrow vs extramedullary relapse of acute leukemia after allogeneic HCT. The mode of relapse needs to be investigated in future reports of acute leukemia treated with allogeneic HCT.

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

Similar content being viewed by others

References

  1. Giralt SA, Champlin RE . Leukemia relapse after allogeneic bone marrow transplantation: a review. Blood 1994; 84: 3603–3612.

    CAS  Google Scholar 

  2. Zittoun RA, Mandelli F, Willemze R et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 1995; 332: 217–223.

    Article  CAS  Google Scholar 

  3. Horowitz MM, Messerer D, Hoelzer D et al. Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. Ann Intern Med 1991; 115: 13–18.

    Article  CAS  Google Scholar 

  4. Au WY, Kwong YL, Lie AKW et al. Review article. Extra-medullary relapse of leukemia following allogeneic bone marrow transplantation. Hematol Oncol 1999; 17: 45–52.

    Article  CAS  Google Scholar 

  5. Chong G, Byrnes G, Szer J, Grigg A . Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy. Bone Marrow Transplant 2000; 26: 1011–1025.

    Article  CAS  Google Scholar 

  6. Lee K-H, Lee J-H, Kim S et al. High frequency of extramedullary relapse of acute leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 2000; 26: 147–152.

    Article  CAS  Google Scholar 

  7. Simpson DR, Nevill TJ, Shepherd JD et al. High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation. Bone Marrow Transplant 1998; 22: 259–264.

    Article  CAS  Google Scholar 

  8. Békássy AN, Hermans J, Gorin NC, Gratwohl A . Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Bone Marrow Transplant 1996; 17: 801–808.

    PubMed  Google Scholar 

  9. De la Cámara R, Figuera A, Steegmann JL et al. Allogeneic bone marrow transplantation for high risk acute lymphoblastic leukemia. Results from a single institution. Bone Marrow Transplant 1992; 9: 433–438.

    PubMed  Google Scholar 

  10. Oliff A, Ramu N-P, Poplack D . Leukemic relapse 5 1/2 years after allogeneic bone marrow transplantation. Blood 1978; 52: 281–284.

    CAS  PubMed  Google Scholar 

  11. Lawson SE, Darbyshire PJ . Use of donor lymphocytes in extramedullary relapse of childhood acute lymphoblastic leukaemia following bone marrow transplantation. Bone Marrow Transplant 1998; 22: 829–830.

    Article  CAS  Google Scholar 

  12. Colombini A, Barzaghi A, Castagneto M et al. Retro-orbital late relapse in a child with leukemia after allogeneic bone marrow transplantation. Acta Haematol 1995; 94: 44–47.

    Article  CAS  Google Scholar 

  13. Fleming DR, Greenwood MF, Garrison J et al. Lymphocyte infusion for delayed extramedullary relapse of acute leukemia following bone marrow transplantation. Leuk Lymphoma 1996; 21: 525–528.

    Article  CAS  Google Scholar 

  14. Schäfer H, Bader P, Kaiserling E et al. Extramedullary relapses at uncommon sites after allogeneic stem cell transplantation. Bone Marrow Transplant 2000; 26: 1133–1134.

    Article  Google Scholar 

  15. Kelch BP, Bulova SI, Crilley P et al. An unusual extramedullary relapse of acute nonlymphocytic leukemia after allogeneic bone marrow transplantation. Am J Clin Oncol 1990; 13: 238–243.

    Article  CAS  Google Scholar 

  16. Au WY, Lie AKW, Liang R, Kwong YL . Isolated extramedullary relapse of acute lymphoblastic leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 24: 1137–1140.

    Article  CAS  Google Scholar 

  17. Forrest DL, Dalal BI, Naiman SC et al. Testicular relapse of acute promyelocytic leukemia after allogeneic BMT. Bone Marrow Transplant 1997; 20: 689–690.

    Article  CAS  Google Scholar 

  18. Ueda S, Kanamori H, Sasaki S et al. Isolated extramedullary relapse in knee joint after allogeneic bone marrow transplantation for Ph ALL. Bone Marrow Transplant 1998; 21: 319–321.

    Article  CAS  Google Scholar 

  19. Riseberg DA, Mulvey KP, Dahut WL et al. Late extramedullary relapse following bone marrow transplant for AML presenting as acute renal failure and leukemic ascites. Bone Marrow Transplant 1994; 14: 1009–1010.

    CAS  Google Scholar 

  20. Michel G, Boulad F, Small TN et al. Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis. Bone Marrow Transplant 1997; 20: 107–112.

    Article  CAS  Google Scholar 

  21. Lee J-H, Lee K-H, Lee J-H et al. Plasminogen activator inhibitor-1 is an independent diagnostic marker as well as severity predictor of hepatic veno-occlusive disease after allogeneic bone marrow transplantation in adults conditioned with busulfan and cyclophosphamide. Br J Hematol 2002; 118: 1087–1094.

    Article  CAS  Google Scholar 

  22. Lee K-H, Lee J-H, Lee J-H et al. Non-myeloablative conditioning regimen of fludarabine, busulfan, anti-thymocyte globulin, and methylprednisolone for allogeneic peripheral blood hematopoietic cell transplantation. Haematologica 2001; 86: 999–1001.

    CAS  Google Scholar 

  23. Przepiorka D, Weisdorf D, Martin P et al. Meeting report. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  24. Sullivan KM . Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 1986; 4: 42–93.

    Article  Google Scholar 

  25. McDonald GB, Hinds MS, Fisher LD et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255–267.

    Article  CAS  Google Scholar 

  26. Bearman SI, Anderson GL, Mori M et al. Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. J Clin Oncol 1993; 11: 1729–1736.

    Article  CAS  Google Scholar 

  27. Choi S-J, Lee K-H, Lee J-H 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.

    Article  CAS  Google Scholar 

  28. Slovak ML, Kopecky KJ, Cassileth PA et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adults acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000; 96: 4075–4083.

    CAS  Google Scholar 

  29. Lee S, Kim D-W, Kim Y-J et al. Influence of karyotype on outcome of allogeneic bone marrow transplantation for adults with precursor B-lineage acute lymphoblastic leukaemia in first or second remission. Br J Hematol 2002; 117: 109–118.

    Article  Google Scholar 

  30. Cornelissen JJ, Carston M, Kollman C et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001; 97: 1572–1577.

    Article  CAS  Google Scholar 

  31. Hassan M, Ljungman P, Bolme P et al. Busulfan bioavailability. Blood 1994; 84: 2144–2150.

    CAS  Google Scholar 

  32. Vassal G, Koscielny S, Challine D et al. Busulfan disposition and hepatic veno-occlusive disease in children undergoing bone marrow transplantation. Cancer Chemother Pharmacol 1996; 37: 247–253.

    Article  CAS  Google Scholar 

  33. Blaise D, Maraninchi D, Archimbaud E et al. Allogeneic bone marrow transplantation for acute acute myeloid leukemia in first remission: a randomized trial of a busulfan–cytoxan versus cytoxan–total body irradiation as preparative regimen: a report from the Groupe d'Etudes de la Greffe de Moelle Osseuse. Blood 1992; 79: 2578–2582.

    CAS  Google Scholar 

  34. Ringdén O, Ruutu T, Remberger M et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report for the Nordic Bone Marrow Transplantation Group. Blood 1994; 83: 2723–2730.

    Google Scholar 

  35. Andersson B, Madden T, Tran HT et al. Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study. Biol Blood Marrow Transplant 2000; 6: 548–554.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Oncology-Hematology, Department of Medicine, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea

    K-H Lee, J-H Lee, S-J Choi, J-H Lee, S Kim, M Seol, Y-S Lee, W-K Kim & J-S Lee

  2. Department of Laboratory Medicine, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea

    E-J Seo, C-J Park & H-S Chi

Authors
  1. K-H Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-H Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S-J Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J-H Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Seol
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y-S Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W-K Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E-J Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C-J Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H-S Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J-S Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K-H Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, KH., Lee, JH., Choi, SJ. et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant 32, 835–842 (2003). https://doi.org/10.1038/sj.bmt.1704223

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704223

Keywords

This article is cited by

Search

Advanced search

Quick links