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.

4278 Imatinib(IM) has become the “gold standard” for the treatment of CML CP. In clinical trials the majority of pts obtain complete hematologic (CHR) and complete cytogenetic (CCyR) responses. The aim of the study was to evaluate the results of treatment by IM in CML CP pts in general practice (outside clinical trials). Patients and methods There are 335 pts with CML in databases in Saint-Petersburg and Leningrad region. Most of them (283/335-84,5%) are ever treated with IM. Disease phases at the time of the start of IM therapy by ELN (from 268/283 evaluable pts) and MDACC (from 256/283 evaluable pts) criteria were: CP – 232 and 215, AP – 28 and 33, BP - 8 and 8 respectively. All 232 pts in CML CP (by ELN criteria) treated since 2001 by IM were included in the study. Before IM 91/232(39%), 114/232(49%) and 17/232 (7,3%) pts were pretreated by hydroxyurea, interferon-alfa with or without hydroxyurea and busulfan. 12/335(4%) pts were undergone alloSCT(6 alive, 6 dead due to progression or TRM) There were 134/232(58%) pts in early (duration before Im ≤ 12 mos) and 98/232(42%) pts in late CP (> 12 mos). In early and late CP, there were 49/123 and 50/89, 40/123 and 23/89, 34/123 and 16/89 evaluable pts with low, intermediate and high Socal score respectively. The predominance of low Sokal score in late CP pts could to be related to survival benefit before imatinib.. The median time before Im for the whole group, for early and late CP pts were 7,4 mos(from 7 days to 132 mons), 1,8 mons (form 7 days to 12 mons) and 39 mons (from 12,1 mos to 132 mos) respectively. Median time of Im therapy was 33 mos (1 - 75 mos) in whole group, 24mons (1 - 73mos) in early and 34mos(2 - 75mos) in late CP pts respectivel Results Estimated overall survival by 6 years was 94,2% in whole group, 97% and 87% in early and late CP pts resp. Only 14/228(6,1%) of evaluable patients died due to CML: 4/130(3%) in early and 10/98(10,2%) in late CP group. 4 pts, resistant to IM, were transplanted: 1 in early CP and 3 in BP. Deathes were due to TRM or disease progression. CHR was achieved by 3 mons in most cases: 82/110(74,5%) and 36/64(56%) pt, in early and late CP, resp. Patients (39 in hole group, 12 in early and 27 in late CP) with CHR before IM were excluded from these analyses. The probability of CCyR by 6 years was 98% in early CP and 82% in late CP (p=0.002). The rate of CCyR was 75% 80/107) vs 31% (14/75) in patients with or without CHR by 3 mons (p=0.00). The same differences were found in early and late CP. CCyR in patients with CHR before IM was the same as in patients with newly obtained CHR by 3 mons on IM. Thereafter we have divided group of pts with late CP according to its duration before IM (very early -<6mons, early late - 6-60 mons and very late ≥60 mons) and compared CCyR in early CP with different subgroups of late CP. Achievement of CCyR was higher in pts in very early(69.1%) and early –late(68.2%) than in very late group(34.6%)(p=0.09) Further subdivisions of the period of 6-60 mos did not reveal any differences. Moreover, when we deleted the patients pretreated with busulfan, the differences were found only between early and early-late phases. We have separately analyzed very late group, it appeared that pretreatment with busulfan severely decreases CCyR (22% vs 81% in with (12 pts) or without (7 pts) busulfan pretreatment, p=0,002. Probably, patients in very late CP is a specific group of patients with preformed very good prognosis. Clonal evolution before treatment (8 pts in early CP and 7 in late CP) did not influence CCyR achievement. The probability of progression to AP/BP was slightly higher in late (6%) than in early CP (3%) (p=0.05). The appearance of clonal evolution was higher in late than in early CP (p=0,0002). Progression to AP/BP was 1% vs 11% in pts with or without CHR by 3 mos resp. (p=0.003). Conclusions Imatinib is efficacious drug in general hematological practice with very high probability of overall survival, CCyR and low risk of progression to AP/BP. CHR is an early and very important predictor for further successful treatment. Achievement of CCyR strongly depends on CHR by 3 mons. Patients with CHR before imatinib have similar CCyR in patients with CHR by 3 mons on imatinib. Pretreatment period predispose patients to clonal evolution on imatinib treatment. Busulfan pretreatment severely decreases probability of CCyR. Disclosures: No relevant conflicts of interest to declare.

4288 Resistance to imatinib could be overcome by new generations of TKIs. Data about the efficacy of second line TKI treatment may help to create a system for prognosing the duration of 2nd line TKI treatment and time of switching from second line TKI treatment to hematopoietic stem cell transplantation. The aim of the study was to evaluate the results of 2nd line TKI treatment in patients resistant or intolerant to imatinib. Patients and methods 44 resistant and 3 intolerant to imatinib pts were included. Cytogenetics with G-banding and PCR with sequencing were performed for evaluation the response and mutations. There were 39, 7 and 1 pts in CP, AP and BP respectively, Patients were treated by three different ATP-pocket inhibitors. The follow-up on 2nd line TKIs was 0.9-48mons (Median - 15.9 mons), median follow-up from diagnosis was 73,9 mons. In prognosis analysis (CHR, cytogenetics, Sokal) intolerant patients were not included. Results Probability of overall survival from diagnosis by 10 years was 85%. Probability of survival from the start of TKI2 by 4 y -90%. There were no differences in survival in pts with primary and secondary resistance, in CP and AP. Patients with low and intermediate Sokal risk did better than patients with high risk (p=0.014, Fig. 1.). 8 pts had T315I mutation when studied on second line TKI therapy. Achievement of CCyR was 50% (58% when T3151 patients were excluded), it was higher in low+intermediate in comparison with high risk pts (60% vs 30%, p=0.091), in CP than in AP (56% vs 20%,p=0.07), in patients with CHR at switching than in those without CHR (72% vs 18%, p=0.014). We failed to find any differences in CCyR achievement in pts with different best cytogenetic response on imatinib (complete, major, minor, minimal responses, absence of cytogenetic response). MCyR depended on the type of resistance - it was higher in secondary, than in primary resistant pts (80% vs 45%,p=0.06, Fig2). Probability of MCCyR loss was 20%, all of them appear during the first year of treatment. It was higher in AP than in CP (40% vs 12%,P=0.04). Probability of 4 years PFS was high - 75%, also without differences in primary vs secondary resistance and even in AP vs CP. Conclusion Second line TKI treatment is very efficacious in imatinib resistant pts. The effect depended on the type of resistance and phase of the disease, CHR at the moment of switching to 2nd line treatment. Disclosures: No relevant conflicts of interest to declare.

4286 AML M-4 with >30% bone marrow myeloblasts was detected in 63 y old woman 2 mo after a diagnosis of chronic myelomonocytic leukemia (CMMLgrade 2). Cytogenetics showed 46, XX, del(5)(q12 q14) (N=4)/46, XX (N=18). Immune-phenotyping showed CD34+ CD117+ CD13+ CD33+ CD38+ HLADR+ CD2+. Leukemia cells were negative for inv (16), BCR/ABL, NPM, TEL/AML1, MLL/AF4, PML/RARA and AML1/ETO. She was RBC-transfusion-dependent. Therapy with cytarabine and daunorubicin and later with FLAG was ineffective and bone marrow myeloblasts increased to >70% with severe granulocytopenia and infection including pulmonary aspergillosis. She then received lenalidomide, 10 mg/d for 21 d every 4 w Bone marrow myeloblasts decreased to about 20% and granulocytopenia resolved. RBC-transfusion–dependence decreased. Cytogenetic and FISH-testing showed no detectable cells with del(5). This has persisted for 5 mo. Disclosures: Off Label Use: Lenalidomide for the treatment of AML with 5q- deletion.