Skip to main content

Advertisement

SpringerLink
Log in

Chronic myelogenous leukemia

Elements of conventional chemotherapy and an overview of autografting in the treatment of the chronic phase

  • Review
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Chronic myelogenous leukemia (CML) consists of a clonal malignancy that arises from a pluripotent hematopoietic stem call. In most cases, neoplastic cells are characterized by the formation of a shortened chromosome 22 called the Philadelphia chromosome. It results from a reciprocal translocation between long arms of chromosomes 9 and 22. A rearranged gene (bcr-abl) is the consequence of this translocation, and it may be considered as the first step toward leukemic transformation. Conventional chemotherapy of CML in the chronic phase is unable to suppress the Ph+ leukemic clone. The treatment with the IFNα may induce an overall cytogenetic response rate of 40–50% of patients. Autografting for patients with CML in chronic phase may induce a 53% overall cytogenetic response rate with a duration of disease-free time and survival from the autograft ranging, respectively, from 4 to 24 mo and from 8 to 40 mo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fialkow, P.I., Gartler, S.M. and Yoshida, A. (1967). Clonal origin of chronic myelocytic leukaemia in man. Proc. Natl. Acad. Sci. USA 58:1468.

    Article  PubMed  CAS  Google Scholar 

  2. Groffen, J., et al. (1984). Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36:93.

    Article  PubMed  CAS  Google Scholar 

  3. Lugo, T.G., Pendergast, A.M., Muller, A.J. and Witte, O.N. (1990). Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247:1079.

    Article  PubMed  CAS  Google Scholar 

  4. Daley, G.Q., Van Etten, R.A. and Baltimore, D. (1990). Induction of chronic myelogenous leukemia in mice by the P210 bcr-abl gene of Philadelphia chromosome. Science 247:824.

    Article  PubMed  CAS  Google Scholar 

  5. De Klein, A., et al. (1982). A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature 300:765.

    Article  PubMed  Google Scholar 

  6. Mc Gahon, A., et al. (1994). Bcr-abl maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood 83:1179.

    CAS  Google Scholar 

  7. Bedi, A., Zehnbauer, B.A., Barber, J.P., Sharkis, S.J. and Jones, R.J. (1994). Inhibition of apoptosis by bcr-abl in chronic myelogenous leukemia. Blood 83:2038.

    PubMed  CAS  Google Scholar 

  8. Bedi, A., et al. (1995). Bcr-abl-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents. Blood 86:1148.

    PubMed  CAS  Google Scholar 

  9. Hehlmann, R., et al. (1993). Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. Blood 82:398.

    PubMed  CAS  Google Scholar 

  10. Silver, T.R., et al. (1999). An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukaemia: developed for the American Society of Hematology. Blood 94:1517.

    PubMed  CAS  Google Scholar 

  11. Chronic Myeloid Leukaemia Trialists’ Collaborative Group (2000). Hydroxyurea versus busulfan for chronic myeloid leukaemia: an individual patient data metaanalysis of three randomized trials. Br. J. Haematol. 110:573.

    Article  Google Scholar 

  12. Gale, R.P., et al. (1998). Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukaemia. The German CML Study Group. Blood 91(5):1810.

    PubMed  CAS  Google Scholar 

  13. Tanaka, M., et al. (1997). Achievement of a complete cytogenetic response with hydroxyurea in a patient with chronic myelogenous leukaemia. Leuk. Res. 21(5):465.

    Article  PubMed  CAS  Google Scholar 

  14. Tamura, T., et al. (1997). Upregulation of interferon-alpha receptor expression in hydroxyurea-treated leucemia cell lines. J. Invest. Med. 45(4):160.

    CAS  Google Scholar 

  15. Vassallo, C., et al. (2001). Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia. Clin. Exp. Dermatol. 26(2):141.

    Article  PubMed  CAS  Google Scholar 

  16. Kato, N., Kimura, K., Yasukawa, K. and Yoshida, K. (1999). Hydroxyurea-related leg ulcers in a patient with chonic myelogenous leukaemia: a case report and review of the literature. J. Dermatol. 26(1):56.

    PubMed  CAS  Google Scholar 

  17. Poros, A. and Nadasky, K. (2000). Leg ulcer in hydroxyurea-treated patients. Haematologia (Budap.) 30(4):313.

    Article  CAS  Google Scholar 

  18. Abhyankar, D., Shende, C., Saikia, T. and Advani, S.H. (2000). Hydroxyurea induced leg ulcers. J. Assoc. Physicians India 48(9):926.

    PubMed  CAS  Google Scholar 

  19. Tarumoto, T., et al. (2000). A case of bilateral heel ulcers associated with hydroxyurea therapy for chronic myelogenous leukemia. Jpn. J. Clin. Oncol. 30(3):159.

    Article  PubMed  CAS  Google Scholar 

  20. Daoud, M.S., Gibson, L.E. and Pittelkow, M.R. (1997). Hydroxyurea dermopathy: a unique lichenoid eruption complicating long-term therapy with hydroxyurea. J. Am. Acad. Dermatol. 36:178.

    Article  PubMed  CAS  Google Scholar 

  21. Ikeda, K., Mita, M., Ishibashi, T., Shichishima, T. and Maruyama, T. (1998). Myositis caused by hydroxyurea in a patient with chronic myelogeneous leukaemia. Rinsho Ketsueki 39(9):676.

    PubMed  CAS  Google Scholar 

  22. Voutsadakis, I.A. (2000). Interferon-alpha and the pathogenesis of myeloproliferative disorders. Med. Oncol. 17(4):249.

    PubMed  CAS  Google Scholar 

  23. Schmidt, M., et al. (2000). Expression of interferon regulatory factor 4 in chronic myeloid leukaemia: correlation with response to interferon alpha therapy. J. Clin. Oncol. 18(19):3331.

    PubMed  CAS  Google Scholar 

  24. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. (1994). Progress in treatment of chronic myeloid leukemia. Interferon alpha versus conventional chemotherapy. New Engl. J. Med. 330:820.

    Article  Google Scholar 

  25. Lauta, V.M. (1995). Interferon and chronic myelogenous leukemia. Med. Oncol. 12:41.

    Article  PubMed  CAS  Google Scholar 

  26. Kloke, O., Niederle, N. and Qui, J.Y. (1993). Impact of interferon alpha-induced cytogenetic improvement on survival in chronic myelogenous leukemia. Br. J. Haematol. 83:399.

    PubMed  CAS  Google Scholar 

  27. Kantarjian, H.M., et al. (1995) and the Leukemia Service; Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon alpha therapy. Ann. Intern. Med. 122:254.

    PubMed  CAS  Google Scholar 

  28. The Italian Cooperative Study Group on Chronic Myeloid Leukemia (1998). Long-term follow-up of the Italian trial of interferon alpha versus conventional chemotherapy in chronic myeloid leukemia. Blood 92:1.

    Google Scholar 

  29. Sokal, J.E. (1987). Prognosis in chronic myeloid leukaemia: biology of the disease vs treatment. Baillieres Clin. Haematol. 4:907.

    Article  Google Scholar 

  30. Montastruc, M., et al. (1995). Response to recombinant interferon alpha in patients with chronic myelogenous leukaemia in a single center: results and analysis of predictive factors. Leukemia 9:1997.

    PubMed  CAS  Google Scholar 

  31. Wetzler, M., Kantarjian, H., Kurzrock, R. and Talpaz, M. (1995). Interferon alpha therapy for chronic myelogenous leukemia. Am. J. Med. 99:402.

    Article  PubMed  CAS  Google Scholar 

  32. Enright, H. and Mc Glave, P.B. (1997). Biology and treatment of chronic myelogenous leukaemia. Oncology 11(9):1295.

    PubMed  CAS  Google Scholar 

  33. Shepherd, P.C., Richards, S.M. and Allan, N.C. (1996). Progress with interferon in CML. Results of the MRC UK CML III study. Bone Marrow Transplant. 17:915.

    Google Scholar 

  34. Rosti, G., De Vivo, A., Zuffa, E. and Baccarani, M. (1996). Interferon-alpha in the treatment of chonic myeloid leukemia. A summary and an update of the Italian studies. Bone Marrow Transplant. 17:911.

    Google Scholar 

  35. Cortes, J., et al. (1996). Results of interferon-alpha therapy in patients with chronic myelogenous leukemia 60 years of age and older. Am. J. Med. 100(4):452.

    Article  PubMed  CAS  Google Scholar 

  36. Kloke, O., Opalka, B. and Niederle N. (2000). Interferon alpha as primary treatment of chronic myeloid leukemia: long-term follow-up of 71 patients observed in a single center. Leukemia 14(3):389.

    Article  PubMed  CAS  Google Scholar 

  37. Steegmann, J., et al. (1999). Interferon alpha for chronic myeloid leukaemia relapsing after allogeneic bone marrow transplantation. Bone Marrow Transplant. 23(5):483.

    Article  PubMed  CAS  Google Scholar 

  38. Guilhot, F., et al. (1993). A multicentric randomized study of alpha 2b interferon and hydroxyurea with or without cytosine-arabinoside in previously untreated patients with Ph-positive chronic myeloid leukaemia: preliminary cytogenetic results. Leuk. Lymphoma 11(Suppl. 1):181.

    Article  PubMed  Google Scholar 

  39. Thaler, J. and Hilbe, W. (1996). Comparative analysis of two consecutive phase II studies with IFN-alpha and IFN-alpha+ARA C in untreated chronic phase CML patients. Bone Marrow Transplant. 17(suppl. 3):525.

    Google Scholar 

  40. Guilhot, F., et al. (1996). On behalf of the French CML Study Group, The treatment of chronic myelogenous leukaemia by interferon and cytosine-arabinoside: rationale and design of the French trials. Bone Marrow Transplant. 17(Suppl.3):S29.

    Google Scholar 

  41. Guilhot, F., et al. Phase I/II trials of the oral Ara-C prodrug YKNO 1 in chronic myelogenous leukaemia patients: haematologic and cytogenetic responses. J. Clin. Oncol., in preparation.

  42. Sokal, J.E., Cox, E.B. and Baccarani, M. (1984). Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 63:789.

    PubMed  CAS  Google Scholar 

  43. Steegmann, J.L., et al. (1999). Stage, percentage of basophils at diagnosis, hematologic response within six months, cytogenetic response in the first year: the main prognostic variables affecting outcome in patients with chronic myeloid leukemia in chronic phase treated with interferon alpha. Results of the CML 89 trial of the Spanish Collaborative Group on Interferon alpha 2a and CML. Haematologica 84(11):978.

    PubMed  CAS  Google Scholar 

  44. Hasford, J., et al. (1998). A new prognostic score for survival of patients with chronic myeloid leukaemia treated with interferon alpha. J. Natl. Cancer Inst. 90:850.

    Article  PubMed  CAS  Google Scholar 

  45. Thomas, M.J., Irving, J.A.E., Lennard, A.L., Proctor, S.J. and Taylor, P.R.A. (2001). on behalf of the Northern Region Haematology Group, Validation of the Hasford score in a demographic study in chronic granulocytic leukaemia. J. Clin. Pathol. 54:491.

    Article  PubMed  CAS  Google Scholar 

  46. Sokal, J.E., Leong, S.S. and Gomez, G.A. (1987). Preferential inhibition by cytarabine of CFU-GM from patients with chronic granulocytic leukemia. Cancer 59:197.

    Article  PubMed  CAS  Google Scholar 

  47. Capizzi, R.L., White, J.C. and Powell, B.L. (1991). Effect of dose on the pharmacokinetic and pharmacodynamic effects of cytarabine. Semin. Haematol. 28:54.

    CAS  Google Scholar 

  48. Sokal, J.E., Gockerman, J.P. and Bigner, S.H. (1988). Evidence for selective antileukemic effect of cytosine-arabinoside in chronic granulocytic leukemia. Leuk. Res. 1:453.

    Article  Google Scholar 

  49. Robertson, M.J., Tantravah, R., Griffin, J.D., Canellos, G.B. and Cannistra, S.A. (1993). Hematologic remission and cytogenetic improvement after treatment of stable phase chronic myelogenous leukemia with continuous infusion of low-dose cytarabine. Am. J. Haematol. 43:905.

    Article  Google Scholar 

  50. Kantarjian, H.M., et al. (1999). Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low dose cytarabine. J. Clin. Oncol. 17:284.

    PubMed  CAS  Google Scholar 

  51. Tothova, E., et al. (2000). Hematological and cytogenetic response of interferon alpha2b alone and combined interferon alpha plus cytarabine as first-line treatment in chronic myeloid leukaemia. Neoplasma 47(2):125.

    PubMed  CAS  Google Scholar 

  52. Giles, F.J., et al. (2000). A prospective randomized study of alpha2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukaemia: the International Oncology Study Group CML1 study. Leuk. Lymphoma 37(3–4):367.

    PubMed  CAS  Google Scholar 

  53. Lindauer, M., et al. (1999). Efficacy and toxicity of IFN-alpha2b combined with cytarabine in chronic myelogenous leukaemia. Br. J. Haematol. 106:1013.

    Article  PubMed  CAS  Google Scholar 

  54. Lindauer, M. and Fischer, T. (2001). Interferon-alpha combined with cytarabine in chronic myelogenous leukaemia—clinical benefits. Leuk. Lymphoma 41(5–6):523.

    Article  PubMed  CAS  Google Scholar 

  55. Giguere, V., Ong, E.S. and Sagui, P. (1987). Identification of a receptor for morphogen retinoic acid. Nature 330:624.

    Article  PubMed  CAS  Google Scholar 

  56. Chambon, P. (1994). The retinoid signaling pathway: molecular and genetic analysis. Semin. Cell Biol. 5:115.

    Article  PubMed  CAS  Google Scholar 

  57. Warrel, R.P. (1994). Applications for retinoids in cancer therapy. Semin. Haematol. 31:1.

    Google Scholar 

  58. Frankel, S.R., et al. (1995). All trans retinoic acid for acute promyelocitic leukemia. Results of the New York study. Ann. Intern. Med. 120:1722.

    Google Scholar 

  59. Avvisati, G., et al. (1996). AIDA (All-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a GIMEMA pilot study. Blood 87:1390.

    Google Scholar 

  60. Visani, G., Tosi, P. and Manfroi, S. (1993). All-trans retinoic acid in the treatment of myelodisplastic syndromes. Leuk. Lymphoma 19:277.

    Article  Google Scholar 

  61. Kuzel, T., Roenig, H., Samnelson, E. and Rosen, S. (1993). The treatment of mycosis fungoides with all-trans retinoid acid. Blood 82(Suppl. 1):570.

    Google Scholar 

  62. Musto, P., et al. (1995). All-trans retinoic acid for advanced multiple myeloma. Blood 85:3769.

    PubMed  CAS  Google Scholar 

  63. Guglielmo, P., et al. (1995). All-trans retinoic acid (ATRA) induced apoptosis in peripheral freshly isolated chronic myeloid leukemia cells. Blood 86:253.

    Google Scholar 

  64. Sagayadan, G.E., et al. (1994). Effect of retinoic acid and interferon alpha on granulocyte-macrophage colony forming cells in chronic myeloid leukemia: increased inhibition by all-trans and 13-cis retinoic acid in advanced stage disease. Leuk. Res. 18:741.

    Article  PubMed  CAS  Google Scholar 

  65. Russo, D., Iacona, I. and Sarchi, S. (1966). for GER (Gruppo Ematologico Retinoidi), Pharmacokinetic profile of all-trans retinoic acid in patients with Ph+ chronic myeloid leukemia in chronic-phase treated with an intermittent schedule. Proc. Sixth International Congress Anticancer Treatment.

  66. Cortes, J., Kantarjian, H. and O’Brian, S. (1996). A pilot study of all-trans retinoic acid in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukaemia. Blood 88(Suppl. I):abstract 3515.

    Google Scholar 

  67. Cortes, J., et al. (1997). A pilot study of all-trans retinoic acid in patients with Philadelphia chromosome-positive chronic myelogenous leukaemia. Leukemia 11(7):929.

    Article  PubMed  CAS  Google Scholar 

  68. Mundle, S., et al. (1994). In vivo effects of retinoic acid (RA) and alpha interferon on proliferation and apoptosis in marrows of acute myelogenous leukemia patients. Blood 84(Suppl. I):312.

    Google Scholar 

  69. Handa, H., et al. (1997). The effects of 13-cis retinoic acid and interferon alpha in chronic myelogenous leukaemia cells in vivo in patients. Leuk. Res. 2(11–12):1087.

    Article  Google Scholar 

  70. Russo, D., et al. (1999). Pilot study of combined therapy with interferon alpha, arabinosyl cytosine and all trans retinoic acid in patients with chronic myeloid leukaemia in the chronic phase. Haematologica 84(2):185.

    PubMed  CAS  Google Scholar 

  71. Sacchi, S., et al. (1999). Unexpected high incidence of severe toxicities associated with alpha interferon, low-dose of cytosine arabinoside and all trans retinoic acid in patients with chronic myelogenous leukaemia. Leuk. Lymphoma 35(5–6):483.

    Article  PubMed  CAS  Google Scholar 

  72. Reiffers, J. Trovette, R. and Marit, G. (1991). Autologous blood stem cell transplantation for chronic granulocytic leukaemia in transformation: a report of 47 cases. Br. J. Haematol. 77:339.

    PubMed  CAS  Google Scholar 

  73. Haines, M.E., Goldman, J.M. and Worsley, A.M. (1984). Chemotherapy and autografting for patients with chronic granulocytic leukaemia in transformation: probable prolongation of life for some patients. Br. J. Haematol. 58:711.

    PubMed  CAS  Google Scholar 

  74. Barnett, M.J., et al. (1989). Successful autografting in chronic myeloid leukaemia after maintenance of marrow in culture. Bone Marrow Transplant. 4:345.

    PubMed  CAS  Google Scholar 

  75. Coulombel, L., Kalousek, D.K., Ecows, C.J., Gupta, G.M. and Eaves, A.C. (1983). Long-term marrow culture reveals chromosomally normal hemopoietic progenitor cells in patients with Ph-positive chronic myelogenous leukaemia. N. Engl. J. Med. 306:1493.

    Article  Google Scholar 

  76. Carella, A.M., Cavaliere, M., Lerma, E. and Corsetti, M.T. (1999). Autologous peripheral blood haematopoietic stem cell transplantation for chronic myelogenous leukaemia. Baillieres Best Pract. Res. Clin. Haematol. 12(1–2):209.

    Article  PubMed  CAS  Google Scholar 

  77. Podesta, M., et al. (2000). Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leucemia induces a prolonged prevalence of Ph-negative hemopoiesis. Exp. Hematol. 28(2):210.

    Article  PubMed  CAS  Google Scholar 

  78. Carella, A.M., Gaozza, E. and Raffo, M.R. (1991). Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy blood cell autograft and cyclosporine. Leukemia 5:517.

    PubMed  CAS  Google Scholar 

  79. Carella, A.M. (1998). Autotransplants in chronic myeloid leukaemia. Oncologist 3:54.

    PubMed  Google Scholar 

  80. Corsetti, M.T., et al. (2000). Cytogenetic response to autografting in chronic myelogenous leucemia correlates with the amount of BCR-ABL positive cells in the graft. Exp. Hematol. 38(3):353.

    Article  Google Scholar 

  81. Turhan, A.G., et al. (1990). Detection of breakpoint cluster region-negative and non clonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow. Blood 76:2404.

    PubMed  CAS  Google Scholar 

  82. Udomsaki, C., et al. (1992). Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level. Proc. Natl. Acad. Sci. USA 89:6192.

    Article  Google Scholar 

  83. Skorski, T., et al. (1993). Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr-abl antisense oligodeoxynucleotides combined with mafosfamide. J. Clin. Invest. 92:194.

    Article  PubMed  CAS  Google Scholar 

  84. Spencer, A., Granter, N., Fagan, K., Zaunders, G. and Deveridge, S. (1998). Collection and analysis of peripheral blood mononuclear cells during haemopoietic recovery following PBSCT for CML: autografting as an in vivo purging manoeuvre? Bone Marrow Transplant. 21:101.

    Article  PubMed  CAS  Google Scholar 

  85. Coutinho, L.H., et al. (1997). Autografting in Philadelphia (Ph)+ chronic myeloid leukaemia using cultured marrow: an update of a pilot study. Bone Marrow Transplant. 19:969.

    Article  PubMed  CAS  Google Scholar 

  86. Carella, A.M. and Frassoni, F. (1996). ICE, Mini ICE or high-dose hydroxyurea to mobilize Philadelphia negative PBPC in chronic myelogenous leukemia. Br. J. Hematol. 95:212.

    Article  Google Scholar 

  87. Carella, A.M., et al. (1993). Collection of “normal” blood repopulating cells during early hemopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukaemia. Bone Marrow Transplant. 12:267.

    PubMed  CAS  Google Scholar 

  88. Barnett, M.J., et al. (1994). Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study. Blood 84:724.

    PubMed  CAS  Google Scholar 

  89. Kantarjian, H.M., et al. (1994). High doses of cyclophosphamide, etoposide and total body irradiation followed by autologous stem cell transplantation in the management of patients with chronic myelogenous leukemia. Bone Marrow Transplant. 14:57.

    PubMed  CAS  Google Scholar 

  90. Carlo-Stella, C., et al. (1994). Autologous transplant for chronic myelogenous leukaemia using marrow treated ex vivo with mafosfamide. Bone Marrow Transplant. 14:425.

    PubMed  CAS  Google Scholar 

  91. Talpaz, M., et al. (1995). Percentage of Philadelphia chromosome (Ph) negative and Ph-positive cells found after autologous transplantation for chronic myelogenous leukemia depends on percentage of diploid cells induced by conventional dose chemotherapy before collection of autologous cells. Blood 86:3257.

    Google Scholar 

  92. Fischer, T., et al. (1998). Chemotherapy-induced mobilization of karyotypically normal PBSC for autografting in CML. Bone Marrow Transplant. 21:1029.

    Article  PubMed  CAS  Google Scholar 

  93. Brito-Bapapulle, F., et al. (1989). Autografting for patients with chronic myeloid leukemia in chronic phase: peripheral blood stem cells may have a finite capacity for mantaining haemopoiesis. Br. J. Hematol. 73:76.

    Google Scholar 

  94. Pratt, G., et al. (1998). Autologous stem cell transplantation in chronic myeloid leukaemia using Philadelphia chromosome negative blood progenitors mobilised with hydroxyurea and G-CSF. Bone Marrow Transplant. 21:455.

    Article  PubMed  CAS  Google Scholar 

  95. Reiffers, J., Goldman, J., Meloni, G. Cahin, J.Y. and Gratwohl, A. (1994). Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation. Bone Marrow Transplant. 14:407.

    PubMed  CAS  Google Scholar 

  96. Simonson, B., et al. (1992). Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia. Leuk. Lymphoma. 7:55.

    Article  Google Scholar 

  97. Johnson, R.J., et al. (1996). Mobilization of Philadelphianegative peripheral blood mononuclear cells in chronic myeloid leukaemia using hydroxyurea and G-CSF (filgrastim). Br. J. Haematol. 93:863.

    Article  PubMed  CAS  Google Scholar 

  98. Lo Coco, T., et al. (1990). Therapy-induced Ph1 suppression in chronic myeloid leukemia: molecular and cytogenetic studies in patients treated with alpha-2b IFN, high-dose chemotherapy and autologous stem cell infusion. Bone Marrow Transplant. 6:253.

    PubMed  Google Scholar 

  99. Mehta, J., et al. (1996). Myelosuppressive chemotherapy to mobilize normal stem cells in chronic myeloid leukemia. Bone Marrow Transplant. 17:25.

    PubMed  CAS  Google Scholar 

  100. Mehta, J., et al. (1996). High-dose hydroxyurea and G-CSF to collect Philadelphia-negative cells in chronic myeloid leukemia: preliminary results. Leuk. Lymphoma 23:107.

    PubMed  CAS  Google Scholar 

  101. Deininger, M.W., Goldman, J.M., Lydon, N. and Melo, J.V. (1997). The tyrosine kinase inhibitor CGP57148 B selectively inhibits the growth of BCR-ABL positive cells. Blood 90(9):3691.

    PubMed  CAS  Google Scholar 

  102. Mahon, F.X. (2001). Chronic myeloid leukemia and tyrosine kinase inhibitors. Rev. Med. Intern. 22(9):894.

    Article  CAS  Google Scholar 

  103. Jorgensen, H.G. and Holyoake, T.L. (2001). A comparison of normal and leukaemia stem cell biology in chronic myeloid leukaemia. Hematol. Oncol. 19(3):89.

    Article  PubMed  CAS  Google Scholar 

  104. Etienne, G. and Mahon, F.X. (2001). Leukemogenesis and new therapy development: the example of chronic myelogenous leukemia. Bull. Cancer 88(7):651.

    PubMed  CAS  Google Scholar 

  105. Le Coutre, P., et al. (1999). In vivo eradication of human BCR-ABL positive leukemia cells with an ABL kinase inhibitor. J. Natl. Cancer Inst. 91(2):102.

    Article  Google Scholar 

  106. Oetzel, C., et al. (2000). The tyrosine kinase inhibitor CGP 57148 B (STI 571) induces apoptosis in BCR/ABL-positive cells by down-regulating BCL-X. Clin. Cancer Res. 6(5):1958.

    PubMed  CAS  Google Scholar 

  107. Fang, G., et al. (2000). CGP 57148 B (STI 571) induces differentiation and apoptosis and sensitises BCR/ABL-positive human leukaemia cells to apoptosis due to antileukemic drugs. Blood 96(6):2246.

    PubMed  CAS  Google Scholar 

  108. Druker, B.J., et al. (2001). Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344(14):1084.

    Article  Google Scholar 

  109. Gorre, M.E., et al. (2001). Clinical resistance to STI 571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 3:293.

    Google Scholar 

  110. Gambacorti-Passerini, C., et al. (2000). Role of alpha 1 acid glycoprotein in the vivo resistance of human BCR-ABL (+) leukemic cells to the abl inhibitor STI 571. J. Natl. Cancer Inst 92(29):1627.

    Google Scholar 

  111. Brouard, M.C., Prins, C., Mach-Pascula, S. and Saurat, J.H. (2001). Acute generalized exanthematous pustolosis associated with STI 571 in a patient with chronic myeloid leukaemia. Dermatology 203:57.

    Article  PubMed  CAS  Google Scholar 

  112. Peters, D.G., et al. (2001). Activity of the farnesyl protein transfrase inhibitor SCH66336 against BCR/ABL-induced murine leukaemia and primary cells from patients with chronic myeloid leukaemia. Blood 97(5):1404.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico, Piazza Giulio Cesare 11-70124, Bari, Italy

    Vito Michele Lauta

Authors
  1. Vito Michele Lauta
    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

Lauta, V.M. Chronic myelogenous leukemia. Med Oncol 20, 95–115 (2003). https://doi.org/10.1385/MO:20:2:95

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/MO:20:2:95

Key Words

Search

Navigation