No Significance of Derivative Chromosome 9 Deletion on the Clearance Kinetics of BCR/ABL Fusion Transcripts, Cytogenetic or Molecular Response, Loss of Response or Treatment Failure to Imatinib Mesylate Therapy for Chronic Myeloid Leukemia.

Abstract Background: Deletion of the derivative chromosome 9 (der 9; del-der9) is a poor prognostic factor in chronic myeloid leukemia (CML) patients treated with hydroxyurea or interferon. However, its prognostic implication in imatinib mesylate (IM) treated patients is unclear. One study reported that IM improved but did not fully reverse the poor prognosis of CML patients with del-der 9, while another suggested that IM might overcome the poor prognostic significance of del-der 9. The purpose of current study is to evaluate the prognostic implication of del-der 9 in CML patients in terms of hematologic, cytogenetic and molecular responses, loss of response to IM and IM treatment failure rate in addition to BCR/ABL mRNA quantitative PCR monitoring. Methods: The current study included 163 CML patients with available FISH results using the LSI-BCR/ABL-(ES) probe (Vysis, IL, USA) treated at the Princess Margaret Hospital (Toronto, Canada). End points of the study included hematologic response (HR), major or complete cytogenetic response (CyR; MCyR/CCyR), major or complete molecular response (MoR; MMoR/CMoR), loss of response (LOR), treatment failure (including primary hematologic or cytogenetic resistance and LOR), progression to accelerated phase or blast crisis (AP/BC), or time to IM dose escalation to achieve further response or to overcome LOR. Results: Of 163 patients, 22 (13.5%) had del-der 9 prior to initiation of IM. No differences were noted between those with and without del-der 9 in terms of disease phase or additional cytogenetic abnormalities. No differences were noted for the time to HR (p=0.598), MCyR (p=0.281), CCyR (p=0.883), MMoR (p=0.125), or CMoR (p=0.834). Times to LOR (p=0.974), treatment failure (p=0.455), progression to AP/BC (p=0.276), or dose escalation of IM (p=0.816) were not significantly different between those with and without del-der 9. The serial monitoring of BCR/ABL mRNA quantitative PCR showed similar patterns of BCR/ABL mRNA reduction between the 2 groups. Conclusion: The presence of del-der 9 in CML patients prior to IM therapy does not influence: the response to IM therapy in terms of HR, CyR and MoR; LOR, treatment failure or progression to AP/BC; and time to dose escalation of IM. Therefore, from the clinical point of view, the presence of del-der 9 does not impact on the management of CML patients treated with IM. Figure 1. No differences of complete cytogenetic response rate (A) or major molecular response rate between patients with versus without deletion of derivative chromosome 9 after imatinib mesylate therapy Figure 1. No differences of complete cytogenetic response rate (A) or major molecular response rate between patients with versus without deletion of derivative chromosome 9 after imatinib mesylate therapy