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The fact that leukaemic cells are primarily or secondarily resistant to cytostatics is a serious phenomenon, which leads to the failure of chemotherapy of malignant diseases in clinical practise. Some detoxification and transporting systems are responsible for the generation of chemoresistance on the cellular level and the decrease of effectiveness in treatment. In vitro testing of chemoresistance of leukaemic cells is presently an inseparable component of “tailoring” therapy in the developing field of predictive oncology. The aim of this work was to estimate profiles of drug resistance, based on the predictive in vitro test, and to help in choosing the most effective cytostatic. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoline (MTT) assay was used, based on the direct effect of cytostatics on the viability of leukaemic cells in vitro. The number of living leukaemic cells was evaluated by a computer program, where LC50 (concentration of cytostatics lethal to 50% of leukaemic cells) was established from the achieved dose-relation curves. Seventy-one samples of leukaemic cells isolated from the patients’ peripheral blood or bone marrow were examined. All samples were tested to 3 cytostatics minimally. It was found by the in vitro assay, that resistance to dexamethasone, prednisolone, etoposide and vincristine is increased in patients with acute myeloid leukaemia disease, compared to the acute lymphoblastic leukaemia patients. In patients with a relapsed disease population, leukaemic cells are highly heterogeneous in the MTT assay. It was concluded that the MTT assay can be used to study drug interactions in vitro in leukaemia samples. The type of interaction was highly different between patients, and depended on drug concentrations.

No relevant conflicts of interest to declare.

Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the number of patients and overall survival increased and quality of life significantly improved. The basic principle of therapy was also changed, according to the clinical practice now it is aimed at early induction of deep molecular response.

Most results on the treatment of chronic myeloid leukemia (CML) with imatinib were obtained from clinical trials that may differ from the routine practice. We report the results of treatment of consecutive CML patients at ten major centers during 2000–2010.Data reporting was retrospective in 2000– 2004 and prospective from 2005 on. A total of 295 patients (137 women and 158 men; median age 49 [range, 15–81]) with Ph+ CML were registered. The median follow-up was 45.4 months (0–113,5).Most patients were treated with first- (169; 57.28%) or second-line (84; 28.5%) imatinib, part of patients underwent allogeneic hematopoietic stem cell transplantation (AHSCT) (28; 9,5%), but 4,7 % were treated with other modalities (14 patients; median age 66 [range, 32–83]). The probability of overall survival (OS) according to Kaplan and Meier at five years was 88.9%, 77.5% and 68.7% for chronic phase patients treated with first-, second-line imatinib and first-line AHSCT, respectively, but only 25.2% for patients receiving other modalities. OS was dependent on the disease phase and Sokal, Hasford and EBMT risk scores (p< 0.001; each). Only 46.2% of deaths in patients treated with other modalities were attributable to CML. Elderly patients over 65 years achieved similar response rates and progression-free survival as the younger. There was a trend for inferior results of AHSCT performed after failure of imatinib (p=0.075), probably due to differences in EBMT risk scores (p< 0.001).Ability to achieve results comparable to previous clinical studies in our CML cohort was influenced by centralized care. Decisions not to initiate imatinib or to delay AHSCT may have a negative impact on OS, but comorbidities may limit the treatment potential of imatinib in the elderly.No relevant conflicts of interest to declare.

Abstract 4439

Imatinib (IM), a selective BCR-ABL tyrosine kinase inhibitor (TKI), is a treatment of choice for newly diagnosed chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP) as it was shown in the IRIS trial. The treatment strategy and response evaluation is based on NCCN or ELN guidelines. Only limited “real life” data of IM impact on pts outcome as well as ELN (European LeukemiaNet) recommendations applicability in daily practice has been published. In the Czech as well as in the Slovak Republic (15 million inhabitants), the treatment of CML patients is centralized in overall 13 centers, capable carrying on both the treatment and laboratory monitoring. There are two CML prospective projects CAMELIA and INFINITY focused on CML pts analysis. Aims. To analyze the treatment response and long-term outcome in consecutive, unselected patients with CP-CML treated with IM and to evaluate the prognostic role of ELN 2006 and 2009 response evaluation. To analyze molecular response in more detail.Altogether 458 consecutively included patients in INFINITY (152 pts) and CAMELIA projects (306 pts) were assessed. For the treatment response evaluation the ELN 2006 and ELN 2009 definitions were used. We assessed rates and the cumulative incidences of complete hematologic responses (CHR), complete cytogenetic responses (CCyR), major (MMoR) and complete molecular responses (CMoR). Overall survival (OS) was defined as the time from the start of IM to death from any cause, overall survival CML-related death (OSCML), transformation-free survival (TFS) as survival without evidence of AP or BP or death from any cause, progression-free survival (PFS) as survival without evidence of AP or BP, loss of CHR, MCyR, increasing white blood cell count or death fron any cause while on IM treatment and event-free survival (EFS) –events defined as a progression (the same as in PFS, as described above), loss of CCyR, failure to achieve CHR at 6 months, MCyR at 12 months and CCyR at 18 months, or intolerance of IM as the cause its discontinution. The patient survival according to MMoR achievement and the cumulative incidence of MMoR according to different BCR-ABL ratio within the first 3 months of IM therapy was analysed. Kaplan-Meier cumulative incidence methods and log rank test were used for survival statistic analysis.A total of 458 patients (median age 52 year;17-81) treated with IM between 2003–2009 were analysed.The median follow-up was 33.1 months (1.4-82.1). At 2 and 4 years the cumulative incidence of CHR was 90.9% and 94.7%, CCyR 64.9% and 76%, MMR 52.4% and 68.1% and CMR 24.5% and 43%, respectively. In 4 years estimated OS was 91.1%, OSCML 96.6%, TFS 93.9%, PFS 83.2% and EFS 66%. According to ELN 2006 criteria the optimal response (OR) by 6 months (defined as PCyR) and by 12 months (defined as CCyR) resp. had significant impact on PFS (p=0.04 and p<0.001 resp.). The optimal reponse by 3 months (defined as CHR) had significant impact on TFS (p<0.001). According to actualized criteria in ELN 2009, the new definition of optimal response in the 3rd month - at least minor cytogenetic response (mCyR), did not show any prognostic impact on PFS. The achievement of MMoR was correlated with the significant improvement in PFS in the 3rd month (p=0.039) as well as in the 12th month (p<0.049). There was significant improvement in EFS for patients in MMoR in all timepoints (p<0.003, <0.001, <0.001, <0.005). The BCR-ABL ratio lower than 1% within the first 3 months was associated with MMoR achievement in higher number of patients in comparison to patients with higher BCR-ABL levels (p<0.001)The excellent and long-lasting efficacy of imatinib in the treatment of CP-CML in non-selected group of patients treated in the defined region was confirmed. Our results are comparable to those achieved in IRIS trial. Response criteria and their predictive role defined by ELN 2006 and 2009 seems to be helpful at some time points, but the ELN 2009 modification does not seem to represent significant improvement compared to ELN 2006. On the other hand based on the present analysis the earlier incorporation of molecular response into the evaluation scheme may be beneficial.CELL-The Czech Leukemia Study Group for Life, Project INFINITY; Project CAMELIA.Faber: BMS, Novartis: Consultancy, Honoraria.

Abstract 1239