Busulfan Exposure Decrease CCyR Rate On Imatinib Therapy - Impact On Recent Pretreatment

Abstract

4452 Imatinib (IM) is now used world-wide as a first line chronic myeloid leukemia (CML) treatment. Although some time lack may exist between diagnosis and IM treatment. Earlier (Blood 2009, 114: Abstract 4278) we have shown that in CML chronic phase (CP) pts with very long history of the disease(more than five years)the pretreatment by Busulfan was the adverse prognostic factor on Imatinib therapy. Now we extend our study by a population of pts recently and for rather short time pretreated by busulfan. Aim. To investigate the effect of busulfan pretreatment on survival and responses to imatinib in CML pts in late CML CP. Materials and methods. In retrospective study 85 pts with CML CP from St-Petersburg, Leningrad region (Russian Federation) and several Ukrainian centers were included. The main inclusion criteria were: CML late CP (the duration of the disease more than 6 mos before IM start), IM therapy in routine clinical practice at least 12 months. The median time of IM therapy was 42,9 mos (12–97 mos), the median age of pts at the IM start was 49,5 years (19–83), male/female ratio 31/54. 23 patients were pretreated with busulfan (the study group) and 62 were not (control group). These groups were equal by age, sex, the median time from diagnosis to the IM start (28,3 mos in the study group and 23,9 in the control group), Sokal risk groups. Median time of busulfan pretreatment was 3,9 mos (1–62 mos). Statistical analysis was performed with SPSS 17. Results. In the whole group of patients frequency of complete cytogenetic response (CCyR) was 60% (51/85), estimated overall survival (OS) by 5 years from IM start was 87% (death rate 7% - 6/85). In the study group CCyR rate was significantly lower, than in the control group: 34,8% (8/23) and 69,35% (43/62), respectively, p=0,038. Estimated OS by 5 years was 72% (death rate 17% - 4/23) for busulfan-pretreated pts and 95% (death rate 3% - 2/62) for the control group, p<0,01. Interestingly, that in the group of shortly busulfan-pretreated pts (the duration of pretreatment ≤6 mos), the lower CCyR rate has also been observed – 31% (4/13), although all other parameters were seemed equal to the control group (median time before IM start 28,3 mos). Conclusion. The pretreatment with busulfan impaired negatively the efficacy of imatinib treatment in CML late CP patients. Even short pretreatment (less than 6 mos) had adverse effect on CCyR. The mechanism is unclear. Busulfan pretreatment before imatinib therapy should not be used. Disclosures: No relevant conflicts of interest to declare.