Position paper on imatinib mesylate in chronic myeloid leukaemia*

British Journal of Haematology (Impact Factor: 4.71). 11/2002; 119(1):268-72. DOI: 10.1046/j.1365-2141.2002.39201.x
Source: PubMed
Download full-text


Available from: Simon Rule, Jan 03, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of patients who achieve CCR after imatinib is unknown. With longer follow-up, it is anticipated that some patients are likely to progress and become candidates for autologous transplantation. We studied filgrastim (r-metHuG-CSF) mobilisation of peripheral blood stem cells (PBSC) in 32 patients who have achieved CCR with imatinib. Our data demonstrate that (1) the target CD34(+) cell yields of >/=2.0 x 10(6)/kg were attained with filgrastim 10 microg/kg/day, in 9/18 (50%) of patients during uninterrupted imatinib therapy, and in 10/14 (70%) when imatinib was temporarily withheld. The median CD34(+) cell yield per aphaeresis was 0.70 x 10(6)/kg (range 0.14-2.18) and 2.90 x 10(6)/kg (range 0.15-8.71) in the two groups, respectively (P&<0.005). (2) The cell yields did not correlate with the duration of imatinib administration. (3) There was no impact of the mobilisation procedure on the level of leukaemia as measured by serial blood bcr-abl levels using real-time quantitative PCR with either protocol. (4) bcr-abl remained detectable at low levels in the harvests in most but not all patients. In conclusion, filgrastim can safely be used to mobilise PBSC in patients who have achieved CCR with imatinib, but CD34(+) cell yields are significantly improved when imatinib is temporarily withheld.
    Leukemia 06/2003; 17(5):821-8. DOI:10.1038/sj.leu.2402917 · 10.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pure red cell aplasia (PRCA) occurred in the fourth month after an ABO-compatible nonmyeloablative allograft coincident with the cessation of immunosuppression and the onset of limited chronic GVHD. No secondary causes could be identified. Erythropoiesis was restored promptly and durably with the resumption of immunosuppression. A clonal T cell receptor gamma rearrangement was detected in peripheral blood lymphocytes prior to the onset of PRCA. PRCA should be added to the list of immunohaematological complications of GVHD.
    Bone Marrow Transplantation 01/2004; 32(11):1099-101. DOI:10.1038/sj.bmt.1704271 · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imatinib is a molecularly targeted therapy that inhibits the oncogenic fusion protein BCR-ABL, the tyrosine kinase involved in the pathogenesis of chronic myelogenous leukemia (CML). Selective inhibition of BCR-ABL activity by imatinib has demonstrated efficacy in the treatment of CML, particularly in chronic phase. Some patients, however, primarily those with advanced disease, are either refractory to imatinib or eventually relapse. Relapse with imatinib frequently depends not only on re-emergence of BCR-ABL kinase activity but may also indicate BCR-ABL-independent disease progression not amenable to imatinib inhibition. Results from phase 2/3 trials suggest that rates of resistance and relapse correlate with the stage of disease and with the monitoring parameters--hematologic, cytogenetic and molecular response. These observations and more recent trials with imatinib, combined with insights provided by an increased understanding of the molecular mechanisms of resistance, have established the rationale for strategies to avoid and overcome imatinib resistance in the management of CML patients. To prevent resistance, early diagnosis and prompt treatment with appropriate initial dosing is essential. Management of resistance may include therapeutic strategies such as dose escalation to achieve individual optimal levels, combination therapy, as well as treatment interruption.
    Leukemia 09/2004; 18(8):1321-31. DOI:10.1038/sj.leu.2403426 · 10.43 Impact Factor
Show more