Stable molecular remission induced by imatinib mesylate (STI571) in a patient with CML lymphoid blast crisis relapsing after allogeneic stem cell transplantation

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Summary:

We report the response to the ABL kinase inhibitor imatinib mesylate (STI571) in a patient with chronic myeloid leukemia (CML) who relapsed twice after dose-reduced allogeneic stem cell transplantation (alloSCT) for B lymphoid blast crisis (BC) and failed to develop an antileukemic response despite grade 3 graft-versus-host disease (GvHD). Complete hematologic, cytogenetic and molecular responses were achieved within 9 weeks of therapy and are maintained after 27 months. Extensive chronic skin GvHD necessitating immunosuppressive therapy developed after 14 months. This case illustrates the ability of imatinib to induce sustained hematologic and molecular remissions in some patients relapsing with advanced stage CML after alloSCT.

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References

  1. 1

    McGlave PB, Shu XO, Wen W et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood 2000; 95: 2219–2225.

  2. 2

    Collins RHJ, Shpilberg O, Drobyski WR et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

  3. 3

    Dazzi F, Szydlo RM, Goldman JM . Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol 1999; 27: 1477–1486.

  4. 4

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

  5. 5

    Arcese W, Goldman JM, D'Arcangelo E et al. Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group. Blood 1993; 82: 3211–3219.

  6. 6

    Druker BJ, Talpaz M, Resta DJ et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

  7. 7

    Kantarjian H, Sawyers C, Hochhaus A et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

  8. 8

    Talpaz M, Silver RT, Druker BJ et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928–1937.

  9. 9

    Druker BJ, Sawyers CL, Kantarjian H et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–1042.

  10. 10

    Kantarjian HM, Cortes J, O'Brien S et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 2002; 99: 3547–3553.

  11. 11

    Ottmann OG, Druker BJ, Sawyers CL et al. A phase II study of Glivec (imatinib mesylate) in patients with relapsed or refractory philadelphia chromosome-positive acute leukemias. Blood 2002; 100: 1965–1971.

  12. 12

    Sawyers CL, Hochhaus A, Silver RT et al. Glivec™ (imatinib mesylate) induces hematologic and cytogenetic responses in patients with chronic myeloid leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–3539.

  13. 13

    Olavarria E, Craddock C, Dazzi F et al. Imatinib mesylate (STI571) in the treatment of relapse of chronic myeloid leukemia after allogeneic stem cell transplantation. Blood 2002; 99: 3861–3862.

  14. 14

    Wassmann B, Klein SA, Scheuring U et al. Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation. Bone Marrow Transplant 2001; 28: 721–724.

  15. 15

    Kantarjian HM, O'Brien S, Cortes JE et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002; 100: 1590–1595.

  16. 16

    Scheuring UJ, Pfeifer H, Wassmann B et al. Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/BCR-ABL positive acute lymphoblastic leukemia (Ph+ALL) with the ABL-tyrosine kinase inhibitor STI571 (Glivec). Blood 2003; 101: 85–90.

  17. 17

    Hochhaus A, Reiter A, Saussele S et al. Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group. Blood 2000; 95: 62–66.

  18. 18

    Thiede C, Florek M, Bornhauser M et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

  19. 19

    Bornhauser M, Thiede C, Brendel C et al. Stable engraftment after megadose blood stem cell transplantation across the HLA barrier: the case for natural killer cells as graft-facilitating cells. Transplantation 1999; 68: 87–88.

  20. 20

    Griesshammer M, Heinze B, Bangerter M et al. Karyotype abnormalities and their clinical significance in blast crisis of chronic myeloid leukemia. J Mol Med 1997; 75: 836–838.

  21. 21

    Martin BA, Rowe JM, Kouides PA, DiPersio JF . Hepatitis B reactivation following allogeneic bone marrow transplantation: case report and review of the literature. Bone Marrow Transplant 1995; 15: 145–148.

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Acknowledgements

We are indebted to S Kriener, MD, for the pathological review of marrow histologies, to Anja Binckebanck for study coordination, to Holger Thüringer, Heike Nürnberger, Martine Pape and Sandra Wagner for their excellent technical assistance, and to U Oelschlägel for FACS sorting.

This work was supported by the BMBF, Competence Network Leukemias, Grant No. 01GI9971, by a grant from the Adolf Messer Foundation, and by Novartis Pharma AG, Nürnberg, Germany.

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Correspondence to O G Ottmann.

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Wassmann, B., Scheuring, U., Thiede, C. et al. Stable molecular remission induced by imatinib mesylate (STI571) in a patient with CML lymphoid blast crisis relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant 31, 611–614 (2003) doi:10.1038/sj.bmt.1703885

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Keywords

  • chronic myeloid leukemia
  • lymphoid blast crisis
  • BCR-ABL
  • tyrosine kinase
  • allogeneic stem cell transplantation
  • molecular remission

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