ALBERT

Beschreibung: Abstract 3260 Poster Board III-1 Background: CML treatment with tyrosine kinase inhibitors induces high and durable rates of complete cytogenetic response. Despite treatment efficacy, a significant proportion of patients develop resistance to these drugs. We measured gene expression profiles in an attempt to identify gene pathways that may be associated with dasatinib resistance. Patients and Methods: Mononuclear cells were separated from peripheral blood samples from seven CML patients resistant to imatinib, collected prior and after dasatinib treatment. Three patients who achieved partial cytogenetic response (Ph-positive cells: 1% - 35%) within twelve months were considered responders (R), whereas four patients who failed to achieve PCyR within 12 months of treatment were classified as non-responders. RNA samples prepared from peripheral mononuclear cells were hybridized to Agilent Technologies 4×44K Whole Human Genome Microarrays (WHGM) and 4×44K intronic-exonic custom oligoarrays. The latter was developed by Verjovski-Almeida's group (Nakaya et al, Genome Biology 2007, 8:R43) and contains sense and antisense probes that map to intronic regions in the human genome representing totally (TIN) and partially (PIN) intronic non-coding RNAs (ncRNAs), in addition to probes for the corresponding protein-coding genes of the same loci. Raw microarray data were normalized by the Affy package in statistical R language implemented in the Bioconductor platform. Each sample was labeled in replicate with Cy3 or Cy5 and the two were considered technical replicates. Two independent statistical approaches SAM (Significance Analysis of Microarrays) and Golub's discrimination score (SNR, Signal to Noise Ratio, with permutations) were performed to identify differentially expressed transcripts between responder and non-responder patients. For the intronic-exonic platform, the analysis parameters were FDR 10%, SNR〉1.5 and p1.5 and p

Beschreibung: Chronic myeloid leukemia (CML) patients with imatinib failure are usually treated with second generation tyrosine kinase inhibitors (TKI). In case of dasatinib or nilotinib intolerance or resistance patients with HLA matched donor are submitted to allogeneic hematopoietic stem cell transplantation (HSCT) or switch treatment to a different TKI. Aims to evaluate complete hematological response (CHR), cytogenetic and molecular responses, overall, progression free and event free survival (OS, FPS and EFS) in CML patients in third line therapy that previously used 2 TKI. BCR-ABL mutations was also evaluated in this population Patients and methods between July 2008 and August 2012 26 CML patients were evaluated: 10 patients (pts) treated with dasatinib (38,5%) and 16 with nilotinib (61,5%) in third line therapy. OS, PFS and EFS were calculated with Kaplan-Meier method and Log-Rank was used for comparison, from the date of the third TKI start. The events for PFS were progression to accelerated phase (AP) or blast crisis (BC) and death. For EFS, were considered loss of CHR, loss of complete cytogenetic response (CCR), TKI discontinuation for failure or intolerance, progression or death. Patients were censored in HSCT date or TKI discontinuation for cytogenetic and molecular responses evaluation, but not for OS. Mutational analysis was done with Sanger sequencing. Results 13 male (50%) and 13 female patients with median age 54 years (22-75) and median follow-up of 32 months were analyzed (1-59). Previous response to imatinib: only one patient has achieved CCR. Status before third TKI start: 19 (73%) less than partial cytogenetic response (PCyR); 2 (7,7%) PCyR; 4 (15,5%) CCR;and 1 (3,8%) clonal evolution. 8/18 (42%) patients presented the following mutations: F317L (2), E255V (1), Y253H (1), M351T (1), M244V (1) e F359V (2). The median time of the third TKI treatment was 171 days (15-1140). Responses to third line TKI: CHR 17/19 (89%) in CP; 3/3 AF; 0/4 BC; CCR: 3/19 in CP (2 pts at 3 months and one in the 12º month); 1/3 AP; 0/4 BC; MMR: 4/19 in CP; 1/3 AP; 0/4 in BC. Nine lost CHR (45%) (8 in CP and one in AP). At 3 months, 1/21 pts (4.5%) achieved MMR; 2/13 (15%) at 6 months, while at 12 months 1/11 (9%) had MMR. At 3 months 11/21 had a BCR-ABL/ABL(IS) 〉10% and at 6 months 10/13 〉1%. Three patients progressed to advanced phases (11,5%) ; 6 (23%) died (4 due to LMC, 1 acute myocardial infarction and 1 from graft vs host disease after HSCT; one lost follow-up. Third line treatment was discontinued in 12 (46%) pts: 6 for resistance, 2 death; 2 intolerance and resistance; 1 intolerance and one loss of follow-up. OS, PFS and EFS were 69%, 68% e 30% respectively(figure 1). OS was inferior in AP and BC in comparison with CP (0% vs 50% vs 90% - p〈 0,0001)(figure 2). In summary responses may be obtained with dasatinib or nilotinib after 2 TKI failure, but they are not durable in advanced phases. Besides the results, that is an alternative for disease stabilization until the identification of a suitable donor or for patients with no performance status for HSCT. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 3289 Poster Board III-1 Imatinib dose escalation has been used in sub-optimal response and therapeutic failure to imatinib in conventional doses. The aim of this study was to evaluate the efficacy of imatinib dose increase in CML patients in CP who did not achieve the best response to imatinib 400 mg QID. Patients and methods: All CML patients in CP treated in our institution with imatinib 400mg between March 2002 and December 2008 were evaluated. Imatinib was escalated to 600–800mg in cases with sub-optimal response or failure, according to Leukemia Net or IRIS Trial criteria. All survival curves were calculated from date of dose increase: overall survival (OS) until death or last follow-up, event free survival (EFS) until loss of complete hematological response (CHR) or major cytogenetic response (MCyR), progression to accelerated phase (AP) or blast crisis (BC) or death from any cause. Transformation free survival (TFS) was calculated from dose increase until progression to AP, BC or death. Results: 137 patients in CP were treated with imatinib 400 mg. Dose was escalated in 55 (40%) patients due to loss or failure to achieve CRH (13 = 24%); progression to BC (2 = 3.5%); no CCR (11 = 20%); loss of RCC (5 = 9%); CCR without major molecular response (MMR) after 18 months of imatinib (24 = 43.5%). Males: 37, females 18 cases. Median age: 44 (16–74) years. Twenty-eight patients (49%) were treated with imatinib as first line therapy and 51% had used IFN previously. Median time between diagnosis and imatinib start was 4.5 (0–94) months. Responses: 94% achieved CHR; 58% CCR and 34% MMR. After dose increase, 31 (56%) responded: 58% of the patients with previous sub-optimal molecular response achieved MMR. Among those who benefited from dose increase, only 3 cases lost the response: one with hematological resistance and two with cytogenetic resistance (2 lost CCR and one CHR). Seven out of 16 patients who increased dose due to cytogenetic failure (loss of response, failure and sub-optimal response) achieved response: one had partial cytogenetic response (PCyR) and 6 CCR. Five patients with hematological failure presented response: CHR (2), CCR (1), PCyR (1) and MMR (1). Patients with BC (2 cases) did not respond to dose escalation. TFS was 89% and 67% in 2 and 5 years, respectively. EFS was 71% and 64% in 2 and 5 years respectively. When stratified by the type of failure, EFS was 100%, 49% and 34% in the group with molecular sub-optimal response with median time of 22 (4–41) months, cytogenetic 17 (1.2–42) and hematological failure 7.7 (0.2–57), respectively (P

Beschreibung: Introduction: Follicular lymphoma (FL) is the second most prevalent non-Hodgkin lymphoma worldwide, and is characterized by an indolent course and frequent relapses. Better understanding of FL has shown that angiogenesis (AG) has an important role in its progression to a more aggressive form. The most important mediator of AG is the vascular endothelial growth factor (VEGF), which is encoded by a polymorphic gene. It is already known that allele C of the VEGF 2578C/A polymorphism (rs699947) is related to higher serum concentration of VEGF compared to the A allele. The roles of this genetic polymorphism in clinical manifestations and outcome of FL are still unknown, and therefore these were the aims of the present study. Methods: Our analysis included 86 consecutive FL patients seen at diagnosis at the university hospital. The patients were treated with 6 to 8 cicles of R-CHOP. The clinical data of these patients were obtained from medical records. Genomic DNA was extracted from peripheral blood samples, and genotyping of the VEGF -2578C/A (rs699947) polymorphism was performed with real-time qPCR. Overall-survival (OS) was defined as time from diagnosis until death from any cause or last follow-up. The differences between groups were analyzed by the logistic regression model. Kaplan-Meier and log-rank analyses were used to assess survival information from the patients’ data. Furthermore, we examined survival data using univariate Cox proportional hazards regression, with the respective hazard ratios (HR) and 95% Confidence Intervals (CIs). Adjustement of Cox regression for clinical features was also performed. A p-value smaller than 0.05 was used to denote statistical significance. Results: The FL patients had a mean age of 56.2 years at diagnosis. The majority of the patients were caucasians (87.6%), and there was an equivalent distribution between genders: 43 male and 43 female patients (50% each). Thirty-nine (45.3%) patients had B-symptoms and 48 (54.7%) had no B-symptoms at diagnosis. Sixty-three (73.2%) patients presented at diagnosis with tumors of III or IV Ann Arbor stage, and 30 (34.8%) had bone marrow infiltration. Follicular Lymphoma International Prognostic Index (FLIPI) was assessed and patients were classified as follows: low-risk FLIPI (≤ 1 point) was seen in 34 cases (39.5%), medium-risk FLIPI (2 points) in 28 cases (32.5%), and high-risk FLIPI ( ≥ 3 points) was seen in 24 patients (27.9%). The VEGF 2578CC genotype was more common in patients with B-symptoms at diagnosis than in those without B-symptoms (51.2% versus 29.7%, p=0.04). The frequency of VEGF 2578CC genotype was also higher in patients with high-risk FLIPI than in those with medium and low-risk FLIPI (58.3% versus 32.2%, p=0.03). We found no association between genotypes and bone marrow infiltration at diagnosis. Considering clinical course of the patients, Kaplan Meier curves of OS showed that at 60 months of follow up, B-symptoms at diagnosis (65.2% of OS versus 87.1%, p=0.02), high-risk FLIPI (52.5% of OS versus 90%, p=0.002), and 2578CC genotype (62.1% of OS in 2578CC patients versus 89.4% in 2578CA plus 2578AA patients, p=0.01) had negative impacts on outcome. In univariate Cox analysis, presence of B-symptoms (p=0.03, HR=3.2, 95% CI: 1.09-9.38), high-risk FLIPI (p=0.01, HR= 3.91, 95% CI: 1.38-11.03) and 2578CC genotype (p=0.02, HR=3.70, 95% CI: 1.16-11.82) were also associated with a worse outcome. The prognostic role of the abovementioned polymorphism was still present after adjustment for age (p=0.04, HR=3.23, 95% CI:1.01-10.36) and Ann Arbor stage (p=0.02, HR=3.58, 95% CI:1.1-11.6) in univariate regression. After adjustment for FLIPI status as a whole, only a trend of association of 2578CC genotype with a worse outcome was found in the study (p=0.05, HR=3.24, 95% CI: 0.95-13.05). Conclusion: Our results present, for the first time, preliminary evidence that FL patients with the VEGF 2578CC genotype, related to higher production of VEGF, are more likely to develop aggressive form of the disease at diagnosis, and to succumb earlier to death. We recognize, however, that our study is based on a small sample size and that more numerous cohorts should be analyzed in order to assess additional associations. Also, further studies, such as correlations between relevant AG genes and tumor vascularization, should be done in order to clarify this issue in the context of FL. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Abstract 1681 Recently the European LeukemiaNet has developed a new scoring system (European Treatment and Outcome Study [EUTOS] score) for newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) treated with imatinib. The EUTOS score classifies patients in high or low risk on the basis of the percentage of basophils in the peripheral blood and the spleen size at diagnosis, with significant correlations with the achievement of an 18-month complete cytogenetic response (CCyR) and progression-free survival (PFS). The aim of this work was to evaluate EUTOS score in CML-CP treated in our center with imatinib as a predictive factor for overall survival (OS), event-free survival (EFS) and PFS. Patients and methods: Between February 2003 and May 2012 consecutive patients with newly diagnosed CML-CP were treated with imatinib 400 mg daily (n= 144) or imatinib 600–800 mg daily (n= 14) were included in the analysis. The criteria recommended by European LeukemiaNet (ELN) were used for the definitions of CCyR and the progression to accelerated phase (AP) or blast phase (BP). The EUTOS score was defined by (7×basophils) plus (4×spleen size) at diagnostic. A EUTOS score of more than 87 indicates high risk, and less than or equal to 87 low risk. EFS was measured from the start of imatinib treatment to the date of any of the following events: death from any cause at any time, loss of complete hematologic response, loss of CCyR, or progression to AP or BP. PFS was measured from the start of treatment to the date progression to AP or BP, last follow-up, or death from any cause. Survival probabilities were estimated by the Kaplan-Meier method and compared by the log-rank test whereas it was applied cumulative incidence for the probability to achieve CCyR. Results: A total of 158 patients were treated, 94 (59.5%) male. The median age at Imatinib was 47 years (17–86 years). The median time from diagnosis to TKI therapy was 2 (0–6) months, with 153 (96.8%) receiving previous treatment with Hydrea. The median follow-up was 29 (1–110) months. The median splenomegaly size was 4 (0–29) cm and the median basophil percentage was 2.5% (0–18%). According to the Sokal score, 43 (34,4%) patients, 46 (36,8%), and 36 (28,8%) were in low, intermediate, and high Sokal score category, respectively (33 not available). Concerning the Hasford score, 60 (48,3%), 50 (40,4%) and 14 (11,3%) were in low, intermediate and high risk categories (34 NA). A total of 137 (86,8%) patients were in the low EUTOS score category and 21 (13,2%) in the high risk category. The cumulative probability of achieving a CCyR and MMR at 36 months for all patients was 78% and 64%, respectively. Patients who had not achieved CCyR after 6 months (51/153 – 33%) had a 2% risk of subsequent progression, which increased to 12% after 12 months, 14% in 18 months and 19% after 24 months. EFS, PFS, and OS rates for the whole group were 60%, 89%, and 92%, respectively. Patients with a low EUTOS score had higher rates of cumulative CCyR compared with patients with high EUTOS score (82% vs. 53%, p= 0.06) (figure 1). There were no differences in the cumulative CCyR rates in patients stratified by Sokal or Hasford scores (and 0.21 and P=0.82, respectively). Patients with CCyR at 18 months had a higher EFS (81% vs. 18%, p〈 0.0001) and PFS rates (96% vs. 82%, p= 0.03). There was no difference in PFS (figure 2) and OS rates between patients with low and high EUTOS score. However, patients with high and intermediate Sokal score had an inferior PFS rates in comparison with low risk group (77%, 84% and 100%, respectively, p= 0.02). There was a superior EFS rates in low risk in comparison with high EUTOS score (63% vs. 36%, p= 0.01) (figure 3), whereas the overall survival there was no difference (91% vs. 100%). Sokal scores EFS rates were 68%, 60% and 40% for low, intermediate and high risk groups respectively (p= 0.03). In conclusion, similarly to the original report, EUTOS score seems to predict CCyR, but not PFS in our population. However, EFS was significantly better in the low than high risk group. The score can discriminate patients with poor outcome, with lower probability of achieving responses to first line imatinib therapy. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: The prognostic significance of BCR-ABL1 transcripts in chronic myeloid leukemia (CML) is controversial. A recent report demonstrated that patients with e13a2 transcripts have inferior outcomes with imatinib 400 mg and those patients with e14a2 or that express both transcripts have more chance of an optimal response and longer event-free and transformation-free survival, while others do not confirm this data.The aim of this study was to evaluate the impact of BCR-ABL transcript type in CML patients outcome.Patients and methods: all consecutive CML patients in chronic phase treated with imatinib 400 mg/day from February 2004 to January 2016 were enrolled. Patients' responses were monitored with cytogenetic analysis at 3, 6 and 12 months, then every six months until a complete cytogenetic response (CCR). Real-time polymerase chain reaction was assessed at baseline, then every 3 months for the first year until reaching a stable major molecular response, then every 3-6 months. Demographic and baseline disease characteristics were collected at diagnosis. The type of BCR-ABL1 transcript was evaluated by multiplex RT-PCR from cDNA synthesized from total leukocytes RNA at diagnosis. We included patients with BCR-ABL transcripts e13a2, e14a2, and with coexpression of e13a2 and e14a2. Statistical analysis: Event-free survival (EFS) was measured from the start of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated (AP) or blast phase (BC) or death from any cause at any time while on initial therapy. Overall survival (OS) was measured from the start of imatinib until to the date of death from any cause at any time or last follow-up. Transformation-free survival (TFS) was measured from the start of imatinib to transformation to AP or BC or deaths while on therapy. The differences between variables were analyzed by the χ2 and the Kruskal-Wallis tests for categorical and continuous variables. Survival probabilities were calculated using the Kaplan-Meier method and compared by the log-rank test. The Cox regression estimated the hazard ratio values. All analysis considering p-value 〈 0.05 and using SPSS 21.0 software. Results: A total of 190 patients were treated with imatinib 400 mg/day. Median age was 48 years (18-87) and Sokal risk was high in 47/151 patients (31%), intermediate in 55/151 (36%) and low in 49/151 (33%). Twenty patients were excluded from the analysis: 14 patients due to Interferon treatment before Imatinib; two patients that started imatinib after six months from diagnosis; two patients with e1a2 transcripts and two patients with no RT-PCR test available at diagnosis. The remaining 170 patients presented typical BCR-ABL1 transcripts: e13a2 (n=56; 33%), e14a2 (n=94; 55%) and both transcripts (n=20; 12%). A total of 44 (26%) patients discontinued imatinib and 24 (14%) switched to second-line tyrosine kinase inhibitor. No differences were observed in sex, age, leukocytes, hemoglobin and platelets count at diagnosis, Sokal or EUTOS score according to transcript type. The proportion of patients with e13a2, e14a2 and both achieving complete cytogenetic response at 6 months was 19/44 (43%); 42/60 (70%) and 9/14 (64%) (P=0.02); and at 12 months was 28/45 (62%); 47/60 (78%) and 11/14 (78%) (P=0.16). However, the proportion of patients with major or lower molecular responses at 18 months was 13/24 (54%), 25/36 (69%) and 6/9 (66%), which was not significantly different. There were no statistical difference in EFS, PFS, and OS among the e13a2, e14a2 and e14a2+e13a2 groups. However, there was a superior 10-year overall survival in patients with transcripts e13a2 compared to e14a2 (alone or coexpressed with e13a2) (93% vs. 73%, P=0.03), although the 5-year overall survival was 96% vs. 88%, respectively (P=NS). In the multivariate analysis, high/intermediate Sokal score and e14a3/e14a3+e14a2 were independent factors for poor OS (P=0.023 and 0.041, respectively).Conclusion: The type of BCR-ABL transcripts did not affect molecular responses. Although patients with e14a2 transcripts presented higher rates of CCR at 6 months, compared to e13a2 or both transcripts, at long term, there was a superior overall survival among patients with transcripts e13a2 compared to e14a2 (alone or coexpressed with e13a2). The biological mechanism responsible for that difference is not known and should be investigated in larger trials. Disclosures Pagnano: Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria.

Beschreibung: Abstract 3787 Dasatinib is effective at inducing complete cytogenetic response (CCyR) in approximately half of chronic myeloid leukemia (CML) patients treated in the chronic phase (CP) after failing imatinib. The aim of this work was to evaluate the role of molecular monitoring in predicting the outcome of patients treated with dasatinib after imatinib therapy. Between 2008 and 2012, it was analyzed 55 consecutive patients with CML with imatinib intolerance or resistance treated in a single center. Patients received dasatinib (50–140 mg) as second or third line therapy. Cytogenetic analysis was performed at 3, 6, 12 and 18 months after dasatinib introduction. BCR-ABL1 transcripts were measured in the blood at 3 months intervals using real-time quantitative PCR (RQ-PCR). Results were expressed as percent ratios relative to an ABL1 internal control. Major molecular response (MMR) was defined as a transcript level ≤ 0.1% on the international scale. Kinase domain (KD) mutations were performed before starting therapy and/or after dasatinib resistance. The probabilities of overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were calculated using the Kaplan-Meier method. An event was defined as the loss of a CCyR or complete hematologic response, progression to AP and BP, death, or discontinuation of dasatinib. The probabilities of cytogenetic and molecular responses were calculated using cumulative incidence (CI) and x2method. Results: 33 patients were male (60%) and 22 female (40%), with median age of 48 years (15–81). At diagnosis Sokal scores were low for 11/34 (32.4%), intermediate for 6 (17.6%) and high for 17 (50%) (21 NA). Thirteen patients had a previous CCyR with imatinib. The median time between diagnosis and dasatinib treatment was 25 (2–223) months. The median follow-up was 12 months. Disease phase at beginning of dasatinib treatment: 32 (58%) CP, 13 (24%) accelerated phase (AP) e 10 (18%) blast phase (BP). Eight-seven percent achieved RHC, 55% CCyR and 38% MMR. At 3 months 67% (25/37) had BCR-ABL1/ABL1 transcript ratio '10%, at 6 months 48% (14/29) ≤ 1% and at 12 months 27% (6/22) RQ-PCR ≤ 0.1%. After introduction of dasatinib, patients with the 3-month BCR-ABL1/ABL1 transcript ratio of 〉10% had a lower chance of achieving CCyR (12.5% vs 81.5%, p= 0.001) and MMR (8.3% vs. 58.3%, p= 0.005). Patients with the 6-month BCR-ABL1/ABL1 transcript ratio of 〉1% had a lower chance of achieving CCyR (8% vs. 75%, p= 0.01) and MMR (26.6% vs. 64.2%, p=0.06) compared with patients with ratio ≤ 1%. The probability of OS, PFS and EFS in 48 months while on treatment was 83%, 70% and 29%, respectively. PFS was 88%, 76% e 11% in CP, AP and BP respectively (p〈 0.0001). EFS was 36%, 32% e 10% in CP, AP and BP (P〈 0.0001). Dasatinib was discontinued in 26/55 because of resistance (12), intolerance (5) or transplant (1). BCR-ABL KD mutations were detected in 13/38 cases, two before (L387M e M351T) and 11 during dasatinib treatment (T315I-6, M244V-2, E255V-1, E499E-1, M351T-1). Patients with mutations had an inferior EFS (p=0,05). In conclusion, this study indicates that evaluation of molecular response at 3 and 6 months can identify patients with less chance of response to dasatinib in patients with imatinib failure. The early identification of patients with poor outcome is important for planning future treatments. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Background: Gastric lymphoma is the most common extra nodal B cell Non Hodgkin Lymphoma and DLBCL accounts for 70% of cases in the stomach. The clinical course is heterogeneous and clinical symptoms, laboratorial abnormalities and Helicobacter pylori and hepatitis B and C infections, in addition to classical IPI factors, have been related to prognosis. Different clinical behaviors may reflect distinct pathogenic mechanisms. In order to improve outcomes, a better characterization of prognostic factors is required. Aim: We aimed to identify factors with a potential prognosis impact in a consecutive series of gastric DLBCL patients diagnosed and treated in three referee Centers in Brazil, Portugual and Italy, by analyzing demographic and clinical characteristics, response to treatment and outcome (overall survival). The clinical picture of European and Brazilian populations was also compared. Patients and Methods: Between January 2010 and May 2015, 104 DLBCL were enrolled in this study. In order to establishing correlations between the clinical features and response to treatment the following parameters were analyzed: clinical symptoms, serum albumin, serum lactate dehydrogenize (LDH),b 2microglobulin, tumor bulky stage of disease, age-adjusted international prognostic index (aaIPI), and response to treatment. Statistical analysis using SPSS software included descriptive analyses, Kaplan-Meyer estimates for overall survival and Cox regression;p values

Beschreibung: The incidence of Grade 3 (hemoglobin [Hb] level 6.5–8 g/dL) or Grade 4 (Hb level 〈 6.5 g/dL) anemia was reported to be 3% with imatinib therapy for newly diagnosed CML in the IRIS trial, with a median follow-up of 19 months and 7% for chronic-phase (CP) chronic myeloid leukemia (CML) after IFN-α failure. However, there is few data regarding development of anemia after long-term follow-up and its causes. The aim of this work was to evaluate the incidence of anemia after at least two years of treatment of CML patients in CP treated with imatinib and to identify other contributing causes of anemia in this population. Patients and Methods Between 2006 and 2010 121 patients with CML were treated with imatinib 400-800 mg in our center. Forty-six patients were excluded from the analysis for accelerated phase at diagnosis (n=20), discontinuation of imatinib before 2 years of treatment (n=21) and 5 for other causes. A total of 65 patients were evaluated. Hb levels were analyzed at diagnosis, at imatinib start, and at two years of imatinib. Anemia developed after the second year of imatinib therapy was classified as grade 1 (Hb level 〈 10.0 g/dL), grade 2 (Hb level of 8.0 to 〈 10 g/dL), or grade 3 (Hb level of 〈 8.0 g/dL) for the purpose of treatment evaluation according to National Cancer Institute (NCI) Common Toxicity Criteria - Version 4.0. Other comorbidities were analyzed. Results The median age was 53 years (24-86 years), 34 male (52%). 38% of the patients did not present other medical conditions. Comorbidities found in 62% of the patients: systemic arterial hypertension (31%), diabetes mellitus (6.7%), cardiopathy (5%), hypothyroidism (6.1%) and renal failure (only one patient with renal dysfunction in dialysis). Two patients received interferon: one prior imatinib and another during pregnancy, requiring interruption of imatinib in this period. Patient’s responses: 54 (83%) achieved complete cytogenetic response (CCR) and 10 lost response; eight of them developed anemia; 7 had (10.7%) partial response, 1 minor response (1,5%), 1 no response and 1 was not available. Fifty-three patients (81.5%) achieved major molecular response, with loss of response during follow-up in 8 cases (12.5%), seven of these developed anemia.The median Hb (g/dL) level was 12.1, 13 and 13.2 at diagnosis, at imatinib start and at 2 years of treatment respectively. Most of the patients developed Hb bellow the reference level (73.8%; n = 48) during the follow-up, after the second year of treatment. Anemia classification according to NCI criteria: 41 cases presented grade 1, 6 (12.5%) grade 2 and one grade 3. Of these, 68.7% (n = 33) had no etiological causes for the anemia, five patients (10.4%) were resistant, two (4.2%) were not adherent to treatment and in 8 cases (16.7%) the etiology of anemia was identified: hypothyroidism (n=1), erosive gastritis (Helicobacter Pylori positive)(n=1), B12 vitamin deficiency (n=2), HIV/AIDS (n=1), pulmonary tuberculosis (n=1) and renal failure (n=2). Fourteen (29.2%) patients had normalization of Hb levels without medical intervention and the majority (56.2%) still persists with the anemic status until the last follow-up. Four (8.3%) patients had resolution of the anemia after switching to a second generation inhibitor and 3 (6.2%) showed clinical improvement after treatment of the cause. In summary, several degrees of anemia may occur in patients with CML on long-term imatinib therapy, most of them not severe. Regular hematological follow-up is required to identify causes not CML related that can be corrected or if related to imatinib toxicity, dose modification or change of therapy. It should be emphasized the importance of investigating secondary causes for anemia, especially in patients with good adherence to treatment and satisfactory therapeutic response. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Background: Gastrointestinal lymphoma represents only 1-4% of the malignant tumors in the gastrointestinal tract and is the most common extranodal site among all types of Non- Hodgkin Lymphomas (NHL). Only 3% of gastric neoplasms are primary lymphomas. Aim: Identification of factors with a potential prognostic impact among all cases with aggressive gastric diffuse large B-cell lymphoma - the clinical characteristics, the response to therapy and overall survival in the Brazilian-Italy Lymphoma registry. Patients and Methods: Between January 1st 2010 and May 1st 2014, 267 patients with DLBCL were recorded of which 41 (15%) had gastric involvement. The following parameters were evaluated to establish correlations with the response to treatment and survival data: clinical symptoms, serum albumin, serum lactate dehydrogenize (LDH), b2 microglobulin, presence of local regional adenopathies, bulky tumor, stage of disease, international prognostic index (IPIa), type of treatment – surgery plus chemotherapy. Results: A total of 41 patients, with a median age of 69 (28-86) years, were enrolled in this study, with a female: male ratio of 1.7:1. Their ECOG performance status was distributed in 44% grade 0; 34% grade 1; 14.6% grade 2 and 7.4% grade 3, whereas IPIa classification was 5 (12.2%) patients with high risk; 14 (34.2%) high-intermediate risk and 22 (53.6%) low- intermediate risk.Stage III-IV was presented in 66% of cases. LDH values were elevated in 17 patients (41.5%), b2 microglobulin value were elevated in 31 patients (75.6%). The test for identification of Helicobacter Pillory (HP) was available in 33 patients and was positive in 9 patients (27%). The most common symptoms included abdominal pain and weight loss (both 86%), dysphagia (80%) and nausea, vomiting (74%). Bulky were found in 27%, plus anemia (44%) and bleeding (25%). Endoscopic examination was realized in 94%, however, only 8% was submitted to surgery. 39 patients received chemotherapy (84% R-CHOP), one Brazilian case died early and one Italian case was lost follow up. Overall 17.5% (7/40) received radiotherapy. The median follow-up time was 14 (1-71) months, with 1-, 2- and 5-year survival rates of 73, 63 and 58%, respectively. It was found the 5-year overall survival (OS) rate differed significantly according to Anemia (p= 0.02) and LDH at the diagnosis (p〈 0.0001). Among Brazilian and Italian patients the difference clinical characteristics were B symptoms (p=0.02); weight loss (p= 0.003); nausea/vomiting (p= 0.002); pain and dysphagia (p〈 0.0001); showing a wider severity in Brazilian group. Although it did not mean a worst outcome. There was no statistically significant differences in terms of OS according to gender (p=0.19); B symptoms (p= 0.12); bleeding at the diagnosis (p= 0.08) and clinical stage (p= 0.14). Furthermore, the only confirmed factor that influenced OS applying Cox Regression was the LDH (HR 8.74, 95% CI: 2.32-32.8; p= 0.001). In conclusion, the median follow-up time of DLBCL group with gastric involvement does not differ in relation to overall DLBCL patients; nevertheless, it was found negative factors for these patients: anemia and increased LDH at the diagnosis. Furthermore, in the Brazilian patients the HP researching is necessary due the high frequency in this population. Disclosures No relevant conflicts of interest to declare.