Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 301-310 , March 2010

Current Status and Perspectives of Tyrosine Kinase Inhibitor Treatment in the Posttransplant Period in Patients with Chronic Myelogenous Leukemia (CML)

  • Evgeny Klyuchnikov

      Affiliations

    • Interdisciplinary Clinic for Stem Cell Transplantation, University of Aachen, Germany
    • ,
  • Nicolaus Kröger

      Affiliations

    • Interdisciplinary Clinic for Stem Cell Transplantation, University of Aachen, Germany
    • ,
  • Tim H. Brummendorf

      Affiliations

    • Department of Hematology and Oncology, University of Aachen, Germany
    • ,
  • Bettina Wiedemann

      Affiliations

    • Interdisciplinary Clinic for Stem Cell Transplantation, University of Aachen, Germany
    • ,
  • Axel Rolf Zander

      Affiliations

    • Interdisciplinary Clinic for Stem Cell Transplantation, University of Aachen, Germany
    • ,
  • Ulrike Bacher

      Affiliations

    • Interdisciplinary Clinic for Stem Cell Transplantation, University of Aachen, Germany
    • Corresponding Author InformationCorrespondence and reprint requests: Ulrike Bacher, MD, Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Martinistrasse 52, 20246 Hamburg, Germany.

Received 30 May 2009 ,Accepted 31 August 2009.

References 

  1. 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
  2. Gambacorti-Passerini C, le Coutre P, Mologni L, et al. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol Dis. 1997;23:380–394
  3. Le Coutre P, Mologni L, Cleris L, et al. In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J Natl Cancer Inst. 1999;91:163–168
  4. Gratwohl A, Brand R, Apperley J, et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2006;91:513–521
  5. Jabbour E, Cortes J, Kantarjian HM, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood. 2006;108:1421–1423
  6. Bacher U, Klyuchnikov E, Zabelina T, et al. The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia-a report from the German Registry covering the period from 1998 to 2004. Ann Hematol. March 2009;[Epub ahead of print]
  7. 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
  8. DeAngelo DJ, Hochberg EP, Alyea EP, et al. Extended follow-up of patients treated with imatinib mesylate (gleevec) for chronic myelogenous leukemia relapse after allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without graft-versus-host disease. Clin Cancer Res. 2004;10:5065–5071
  9. Olavarria E, Ottmann OG, Deininger M, et al. Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2003;17:1707–1712
  10. Carpenter PA, Snyder DS, Flowers ME, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007;109:2791–2793
  11. Palandri F, Amabile M, Rosti G, et al. Imatinib therapy for chronic myeloid leukemia patients who relapse after allogeneic stem cell transplantation: a molecular analysis. Bone Marrow Transplant. 2007;39:189–191
  12. Atallah E, Kantarjian H, De Lima M, et al. The role of dasatinib in patients with Philadelphia (Ph) positive acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML) relapsing after stem cell transplantation (SCT). Blood. 2006;108:4520
  13. Klyuchnikov E, Schafhausen P, Kroger N, et al. Second-generation tyrosine kinase inhibitors in the post-transplant period in patients with chronic myeloid leukemia or Philadelphia-positive acute lymphoblastic leukemia. Acta Haematol. 2009;122:6–10
  14. Hess G, Bunjes D, Siegert W, et al. Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study. J Clin Oncol. 2005;23:7583–7593
  15. Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007;109:58–60
  16. Olavarria E, Siddique S, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110:4614–4617
  17. Savani BN, Montero A, Kurlander R, et al. Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36:1009–1015
  18. Appel S, Balabanov S, Brummendorf TH, et al. Effects of imatinib on normal hematopoiesis and immune activation. Stem Cells. 2005;23:1082–1088
  19. Appel S, Boehmler AM, Grunebach F, et al. Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells. Blood. 2004;103:538–544
  20. Taieb J, Maruyama K, Borg C, et al. Imatinib mesylate impairs Flt3L-mediated dendritic cell expansion and antitumor effects in vivo. Blood. 2004;103:1966–1967
  21. Boissel N, Rousselot P, Raffoux E, et al. Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. Leukemia. 2004;18:1656–1661
  22. Dewar AL, Doherty KV, Hughes TP, et al. Imatinib inhibits the functional capacity of cultured human monocytes. Immunol Cell Biol. 2005;83:48–56
  23. Cwynarski K, Laylor R, Macchiarulo E, et al. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia. 2004;18:1332–1339
  24. Leder C, Ortler S, Seggewiss R, et al. Modulation of T-effector function by imatinib at the level of cytokine secretion. Exp Hematol. 2007;35:1266–1271
  25. Dietz AB, Souan L, Knutson GJ, et al. Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood. 2004;104:1094–1099
  26. Kantarjian H, Talpaz M, O'Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004;103:2873–2878
  27. Rea D, Legros L, Raffoux E, et al. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006;20:400–403
  28. Mattiuzzi GN, Cortes JE, Talpaz M, et al. Development of Varicella-Zoster virus infection in patients with chronic myelogenous leukemia treated with imatinib mesylate. Clin Cancer Res. 2003;9:976–980
  29. Ikeda K, Shiga Y, Takahashi A, et al. Fatal hepatitis B virus reactivation in a chronic myeloid leukemia patient during imatinib mesylate treatment. Leuk Lymphoma. 2006;47:155–157
  30. Lin JT, Lee MY, Hsiao LT, et al. Pulmonary nocardiosis in a patient with CML relapse undergoing imatinib therapy after bone marrow transplantation. Ann Hematol. 2004;83:444–446
  31. Mumprecht S, Matter M, Pavelic V, et al. Imatinib mesylate selectively impairs expansion of memory cytotoxic T cells without affecting the control of primary viral infections. Blood. 2006;108:3406–3413
  32. Sinai P, Berg RE, Haynie JM, et al. Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo. J Immunol. 2007;178:2028–2037
  33. Bocchia M, Gentili S, Abruzzese E, et al. Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet. 2005;365:657–662
  34. Bocchia M, Abruzzese E, Forconi F, et al. Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia. Leukemia. 2006;20:142–143
  35. Burke MJ, Trotz B, Luo X, et al. Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival. Bone Marrow Transplant. 2009;43:107–113
  36. Larmonier N, Janikashvili N, LaCasse CJ, et al. Imatinib mesylate inhibits CD4+ CD25+ regulatory T cell activity and enhances active immunotherapy against BCR-ABL- tumors. J Immunol. 2008;181:6955–6963
  37. Magro L, Catteau B, Coiteux V, et al. Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD. Bone Marrow Transplant. 2008;42:757–760
  38. Branford S, Rudzki Z, Walsh S, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood. 2003;102:276–283
  39. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20:1767–1773
  40. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12:7374–7379
  41. Hochhaus A, La RP. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia. 2004;18:1321–1331
  42. Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007;109:5143–5150
  43. O'Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005;65:4500–4505
  44. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–141
  45. Tanaka R, Kimura S. Abl tyrosine kinase inhibitors for overriding Bcr-Abl/T315I: from the second to third generation. Expert Rev Anticancer Ther. 2008;8:1387–1398
  46. Aichberger KJ, Herndlhofer S, Agis H, et al. Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukaemia occurring during imatinib therapy. Eur J Clin Invest. 2007;37:808–813
  47. Altintas A, Cil T, Kilinc I, et al. Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report. J Neurooncol. 2007;84:103–105
  48. Petzer AL, Gunsilius E, Hayes M, et al. Low concentrations of STI571 in the cerebrospinal fluid: a case report. Br J Haematol. 2002;117:623–625
  49. Ocheni S, Iwanski GB, Schafhausen P, et al. Characterisation of extramedullary relapse in patients with chronic myeloid leukemia in advanced disease after allogeneic stem cell transplantation. Leuk Lymphoma. 2009;50:551–558
  50. Porkka K, Koskenvesa P, Lundan T, et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008;112:1005–1012
  51. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37
  52. Baccarani M, Pane F, Saglio G. Monitoring treatment of chronic myeloid leukemia. Haematologica. 2008;93:161–169
  53. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–1820
  54. Kantarjian H, Schiffer C, Jones D, et al. Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood. 2008;111:1774–1780
  55. Kaeda J, O'Shea D, Szydlo RM, et al. Serial measurement of BCR-ABL transcripts in the peripheral blood after allogeneic stem cell transplantation for chronic myeloid leukemia: an attempt to define patients who may not require further therapy. Blood. 2006;107:4171–4176
  56. Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76:2462–2465
  57. Porter DL, Roth MS, McGarigle C, et al. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med. 1994;330:100–106
  58. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood. 1995;86:2041–2050
  59. Collins RH, 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
  60. Michallet AS, Nicolini F, Furst S, et al. Outcome and long-term follow-up of alloreactive donor lymphocyte infusions given for relapse after myeloablative allogeneic hematopoietic stem cell transplantations (HSCT). Bone Marrow Transplant. 2005;35:601–608
  61. Weisser M, Tischer J, Schnittger S, et al. A comparison of donor lymphocyte infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation. Haematologica. 2006;91:663–666
  62. Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 1995;86:1261–1268
  63. Deininger M, Schleuning M, Greinix H, et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica. 2006;91:452–459
  64. Oehler VG, Gooley T, Snyder DS, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood. 2007;109:1782–1789
  65. Gontarewicz A, Balabanov S, Keller G, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood. 2008;111:4355–4364

 Financial disclosure: See Acknowledgments on page 308.

PII: S1083-8791(09)00400-5

doi: 10.1016/j.bbmt.2009.08.019

Biology of Blood and Marrow Transplantation
Volume 16, Issue 3 , Pages 301-310 , March 2010

Article Tools