ALBERT

Description: Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.

Description: Introduction: Over half of patients with chronic myeloid leukemia (CML) in sustained deep molecular remission do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in controlled clinical trials, but there is scarce information on its applicability in the real-life setting. We aimed to assess if treatment cessation was feasible in clinical practice in a large nationwide series of CML patients from Spain. Methods: This retrospective study comprised a series of 236 patients in chronic-phase CML who discontinued TKI treatment outside of clinical trials between April 2009 and February 2018 in 33 Spanish institutions. Inclusion criteria were: a) TKI treatment duration 〉3 years; b) sustained MR4.5 in 〉4 consecutive determinations (one single point in MR4 was acceptable) during 〉2 years; c) molecular monitoring in a reference laboratory expressing the results on the International Scale (IS). Patients who had undergone allogeneic hematopoietic stem-cell transplantation were excluded. Molecular relapse was defined as consecutively detectable BCR-ABL1 transcripts showing a ≥1 log increase or loss of MMR in any single sample. Treatment-free remission (TFR) was estimated by the method of Kaplan-Meier and defined as the time from TKI discontinuation to the date of restarting therapy for any reason or, if treatment was not restarted, the date of last contact. Incidence of molecular relapse was calculated using the cumulative incidence function with resumption of TKI treatment in the absence of molecular relapse and death in MMR as competing events. Analysis of factors predicting molecular relapse was done by the method of Fine and Gray. Results: Table 1 shows the main characteristics of the series. Median follow-up from treatment discontinuation was 21.5 months, and 5 patients died in MMR due to CML unrelated causes. TKI therapy was reinitiated due to molecular relapse (MMR loss: n=52, increase 〉1 log in BCR-ABL transcript level at two consecutive assessments without losing MMR: n=12), patient preference (n=2), and severe withdrawal syndrome (n=1). One additional patient lost MMR after 20 months from treatment cessation but decided not to be retreated, with spontaneous recovery of MMR. The probability of TFR at 4 years was 64% (95% Confidence Interval [CI]: 55%-72%)(Figure 1). The cumulative incidence of molecular recurrence was 33% (95% CI: 26%-38%) at 3 years (Figure 2). Forty-nine relapses (75% of total) occurred in the first 6 months. The latest MMR loss was detected 30 months after treatment stop. One patient restarted treatment 44 months after TKI discontinuation due to ≥1 log increase in BCR-ABL1 transcripts in two consecutive samples without losing MMR. In univariate analysis, duration of TKI treatment of less than 5 years (P=0.005) and time in RM4.5 shorter than 4 years before TKI discontinuation (P=0.003) were both significantly associated with a higher incidence of molecular recurrence. No patient progressed to the advanced phases of CML. At the time of restarting treatment, the median BCR-ABL1 IS was 0.3%, with this value being 〉5% in only 7 instances. Most patients (81%) received the same TKI that they were taking before the trial of treatment cessation. Median follow-up after treatment resumption was 20 months. Among the 64 patients who restarted treatment due to molecular relapse, 46 of 52 cases regained MMR after a median time of 3 months, and 47 of 64 regained MR4.5 after a median time of 5 months. Response status at last control was: MR4.5 (n=196), MR4 (n=15), MMR (n=14), complete cytogenetic response (n=10), and other (n=1). Fifty-one patients (22%) developed musculoskeletal or joint pain after treatment cessation. In patients stopping imatinib, a significant increase in Hb levels, leukocyte counts, total lymphocyte counts, platelet counts, and cholesterol levels was observed. At 6 months, an increase in Hb level 〉2 g/dL was observed in 47% of patients with anemia. By contrast, nilotinib discontinuation was not followed by any relevant change in laboratory values. Conclusions: Our results confirm that treatment discontinuation is feasible and safe in clinical practice in Spain. Duration of TKI treatment of less than 5 years and a time in RM4.5 shorter than 4 years before TKI discontinuation were significantly associated with a higher incidence of molecular recurrence. Disclosures Hernandez Boluda: Incyte: Consultancy; Novartis: Consultancy. García Gutiérrez:Incyte: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Ferrer Marin:Incyte: Consultancy; Novartis: Consultancy, Research Funding. Cervantes:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hospital Clinic Barcelona: Employment.

Description: Abstract 1121 Poster Board I-143 The Spanish Registry on CML ( RELMC ) is a multicentric, hospital-based cancer registry whose aim is to describe what is the actual treatment received by patients with CML in Spain, its outcome, and the variables which influence it. Aim To study the variables which could influence the outcome in newly diagnosed CML patients treated with Imatinib, including classic and new variables, such as phosphate serum levels, which are diminished in a substantial number of patients ( Osorio et al,2007) Patients 207 CP-CML patients, newly diagnosed, were included in 17 Spanish hospitals. Sex: 131 M,76F( 63%,37%). Age: Median: 51,5 (18,7-87,5).The risk group distribution was as follows: Sokal L/I/H: ((47%;35%;18%). Hasford ( 44%,49%,7%). The variables studied at diagnosis were sex, Sokal and Hasford group. During the treatment: dose of Imatinib, anemia, neutropenia, thrombocytopenia and hypophosphatemia. Results Median follow up of the series have been 19,1 months. Among 207 patients, frequency values for anemia, neutropenia, and thrombocytopenia were 21%, 29% and 11%, respectively. Ninety-one patients had serum phosphate measured during the treatment. Among them, 49(54%) had hypophosphatemia. Complete hematologic response ( CHR) was obtained in 94,6%.No significant association was found between Sokal or Hasford group and the achievement of complete HR. Complete cytogenetic response (CCR ) was obtained in 73%. A significant association was found between obtaining CCR and Low or intermediate Hasford group (p=0,013) or having hypophosphatemia during the treatment ( p=0,04). The probability of obtaining CCR was higher in patients having hypophosphatemia in the 9th month of therapy (Log Rank (Mantel-Cox) Chi2: 6,21 (p=0,013).Patients who had hypophosphatemia during the treatment also showed a trend for higher probability of CCR (p=0,096). Major and complete molecular response (MMR, CMR) were obtained in 71% and 48%, respectively. MMR was significant worse in Hasford high-risk patients (Pearson Chi-Square:6,909 (p=0,009), and the probability of MMR was higher in patients developing hypophosphatemia ( p=0,175). Regarding CMR, Hasford high risk had a significant association with worse rate of CMR (Chi-Square: 4,419; p=0,036. Also, the probability of CMR was significantly higher in patients having hypophosphatemia ( p=0,045). Conclusion In our series, Hasford risk system has a stronger predictive value than the Sokal classification. It is interesting to note that half of our patients had hypophosphatemia during the treatment with Imatinib. Intriguingly, having low serum levels of phosphate during treatment is associated with better response, and it invites to further study of the biological basis of this finding and its relevance as prognostic variable. This study has received the grant PI07/91015 from the Instituto de Salud Carlos III. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 1898 Poster Board I-921 Introduction: JAK2V617F mutation is detected in more than 90% of cases of polycythemia vera (PV) and in about 50% of cases of essential thrombocythemia (ET). Recently, JAK2-exon 12 and MPL mutations have been reported in myeloproliferative neoplasms (MPN). All these three mutations have a disease causing potential. There are still 50% of ET and PMF patients negative for JAK2V617F mutation. Thus, further genetic analysis to identify novel disease-related aberrations in MPN is required. Methods: We performed whole genome analysis on granulocytic DNA of 45 MPN patients (19 PV and 26 ET) using the single nucleotide polymorphism (SNP) Array 6.0 platform [Affymetrix 6.0]. Genotypes were analyzed using Genotyping Console 3.0.2. Data were normalized against a commercial and an own set of reference samples. All patients had JAK2V617F screening performed. Clinical and analytical data and results of cytogenetics study performed at diagnosis of MPN were colected from clinical reports. Results: From 45 MPN patients, 41 had normal cytogenetics at diagnosis; there were no data concerning cytogenetics study from the rest 4 patients. Using SNP-A 6.0 platform, we detected aberrations (gain or loss of the molecular material) in the following regions: 1q12, 9p1, 17q21, 4q, 3q26 and 8p12. Aberrations in a region 1q12 (n=14) were presented in 8 of PV (gain in 3 and loss in 5) and in 6 of ET (gain in 2 and loss in 4) patients. Aberrations in a region 9p1 (n=27) were observed in 11 of PV (gain in 6 and loss in 5) and in 16 of ET (gain in 10 and loss in 6) patients. Aberrations in a region 17q21 (n=26) were presented in 11 of PV (gain in 3 and loss in 8) and in 15 of ET (gain in 9 and loss in 6) patients. Aberrations in the region 4q (n=20) were detected in 8 of PV (gain in 5 and loss in 3) and in 12 of ET (gain in 9 and loss in 3) patients. Interestingly, only the gain of the molecular material was detected in a region 3q26 (n=12; 5 PV and 7 ET patients). In case of aberration in a region 8p12 (n=20), all 12 ET patients presented gain of the molecular material, whereas PV patients had gain (n=3) or loss (n=3) of the molecular material. There were no relation between the presence of these aberrations and the status of the JAK2V617F mutation, analytical data or clinical outcome of the patients. Conclusions: 1. As we know, patients with ET have low frequency of cytogenetics aberrations. Nevertheless, using SNP-A 6.0 platform [Affymetrix 6.0], it is possible to detect new genomic aberrations in these group of patients. 2. According to our results, gain in 8p12 region is especially related to ET patients. Recently has been reported that, in a 8p12 region there is localized gen INDOL1 that, may be involved in the inhibition of immune response to tumours. 3. Gain in a 3q26 region can be related with both PV and ET. In this region, there are localized two microRNA: hsa-mir-1263 and has-mir-720. 4. SNP-A 6.0 technology should not replace conventional cytogenetics in study of MPN patients. However, SNP-A 6.0 platform, as a high resolution assay, can be useful in identification of new genomic abnormalities that may be relevant for pathogenesis of MPN. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction:Renal impairment (RI) is a common complication in multiple myeloma (MM) with an incidence of 20-40%, due to the older age of the affected patients (pts) and the nature of the disease. Prognosis of pts with RI has improved in recent years (yrs), but remains closely associated with the recovery of renal function. There is little information on the renal response of relapsed refractory MM (RRMM) to new antimyeloma drugs within clinical practice, using standardized criteria such as glomerular filtration rate (GFR) estimated by the Cockroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas.The primary objective of the study is to describe the renal response in RRMM pts with moderate (CrCl 30–50 mL/min) or severe renal impairment (RI) (CrCl 〈 30 mL/min) after initiating treatment (Tx). Secondary objectives include response rate, overall survival (OS), safety, and health resource utilization. We present results from a pre-planned, interim analysis with a data cut-off of June 15, 2014. Methods:This is a large ongoing observational, prospective, multicenter study in RRMM pts with moderate or severe RI (based on the CG formula) receiving antimyeloma Tx. The overall planned sample size is 300 pts to be followed for up to 36 months (mos) after the end of Tx. Renal and MM responses are evaluated according to the International Myeloma Working Group criteria. Renal complete response (renalCR) is defined as a sustained (for at least 2 mos) increase of baseline estimated glomerular filtration rate (eGFR) to ≥ 60 mL/min; a partial renal response (renalPR) is defined as an increase from 〈 15 to 30–59 mL/min, and a minor renal response (renalMR) from 〈 15 to 15–29 mL/min or, from 15–29 to 30–59 mL/min. Results:A total of 150 pts were included in the interim analysis, mean ± SD age was 74 ± 9 yrs, 53% were male, and 53% had moderate and 47% had severe RI. At baseline, 57% of pts were in first relapse. At diagnosis, 45% of pts had ISS stage III, 29% had ISS stage II, 9% had ISS stage I, and 17% had no ISS stage available. Main antimyeloma therapies were: lenalidomide (LEN)-based (37%), bortezomib (BORT)-based (30%), BORT + LEN based (5%), chemotherapy-based (25%) and, thalidomide-based (3%). The median follow-up was 4 mos. To date 38% of pts have discontinued Tx, 13% due to adverse events (AEs), and 29% have died. The main causes of death were: disease progression (8.7%), infection (6.7%), respiratory failure (3.3%), kidney insufficiency (2%), fractures (2%). The mean baseline CG/MDRD was 39.7/42.2 (± 6.3/10.2) mL/min in the moderate RI subgroup and 20.2/19.8 (± 7.6/9.8) mL/min in pts with severe RI (correlation coefficient CG vs. MDRD: 0.93). Overall, 15.3% (n = 23; 95% confidence interval [CI] 9.5–21.1,) had a renal response according to the CG formula, i.e. renal function iimproved by at least 1 KDIGO stage; 4.7% had renalCR, 0.7% renalPR and 10% renalMR. According to the MDRD formula, the renal response was 21.3% (8.6% renalCR, 12.7% renalMR). Median time to best renal response was 1.5 (range 0.6–4.6) mos. The renal response based on CG/MDRD according to antimyeloma therapies was 10.9%/20% for LEN-based, 26.7%/31.1% for BORT-based, 0%/12.5%, for LEN + BORT-based, and 10.2%/15.4%, for chemotherapy-based therapies. 24 hour (hr) proteinuria measurement was available at baseline in 70 pts (median of 1.3 g/24 hr), 77.1% of whom had 〉 0.3g/24 hr. Of these, 4 (7.4%) achieved complete proteinuria response (〈 0.3g/24 hr) and 4 (7.4%) achieved partial response (〈 1g/24 hr) by the 4th follow-up visit. The overall myeloma response (≥ partial response) was 38.0% achieved after a median of 2.9 (1.3–5.2) mos. LEN-based myeloma response was 45.5%, BORT-based 48.9% and LEN + BORT-based 50.0%. These responses seemed to be higher than those obtained with chemotherapy-based therapies (17.6%). The median time to progression (TTP) was 4.5 mos (95% CI 4.2–7.3). TTP was 16.2 mos with LEN-based, 11.8 mos with BORT-based, not reached with LEN + BORT-based, and 8.3 mos with chemotherapy-based therapies. Overall, 52% of pts had an AE and 12% a serious related AE. Conclusions: The most commonly used Tx in clinical practice in RRMM pts with RI are LEN or BORT-based. The results of this interim analysis suggest that these Tx can improve RI in approximately 15% of cases, and are associated with a higher antimyeloma response than chemotherapy-based Tx. Disclosures Morales: Celgene: Consultancy. Ruiz Boza:Celgene : Employment, Other. Garcia:Celgene: Honoraria.

Description: INTRODUCTION The incidence of secondary cancer (SC) in patients with myeloproliferative neoplasms (MPN) is high and comparable to that of thrombosis. However, the identification of patient subgroups that might be at increased susceptibility of developing SC has not been systematically addressed. We report here the results of an international case-control study (MPN-K) aimed at comparing the frequency of exposure to possible causes of SC in patients with classical MPN, polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). METHODS This European Leukaemia Network (ELN) study reports MPN patients from 28 sites of 5 European countries and Israel, diagnosed in the period from 2000 to 2016. Cases were MPN patients with concomitant diagnosis of a non-myeloid SC (n=15) or its presentation during the course of the disease (n=412). Controls were MPN patients cancer-free, matched to the paired case for sex, age (±5 years), date of MPN diagnosis (±5 years), and MPN disease duration (±6 years). A multivariable conditional logistic regression model was used to estimate the effect of selected variables on total SC risk and in different types of SC. RESULTS Among 1,259 MPN patients, there were 427 cases and 832 matched controls. Cases presented melanoma (n=20; 4.7%), non-melanoma skin cancer (n=69; 16.2% - basal/squamous cell carcinoma), non-skin solid cancer (n=290; 67.9%) including breast, ovary/uterus, colorectal, upper gastrointestinal, liver/pancreas, lung, prostate/urinary, other and lymphoproliferative diseases (n=48; 11.2%) including multiple myeloma, chronic lymphocytic leukemia, low and high grade B- and T-lymphoma. At diagnosis, there were slightly more patients with PV among SC cases (n= 152; 35.6%) than controls (n=256; 30.8%), while conversely there were slightly less ET patients among cases (n=196; 45.9%) than controls (n=426; 51.2%). Cases and controls presented similar proportion of MF diagnosis (n=79 cases, 18.5% and 150 controls, 18.0%). Driver mutations (JAK2 V617, EXON-12, CALR, MPL), non-driver mutations and abnormal karyotype were equally represented in cases and controls. Other variables such as cardiovascular risk factors, exposure to cancerogens, family history of cancer and chronic inflammatory diseases were reported with similar frequency in cases and controls. After MPN diagnosis, exposure to first and other lines of treatments until the index event, with Phlebotomy (n=193; 15.3%), Hydroxyurea (n=814; 64.7%), Anagrelide (n=14; 1.1%), Interferon (n=30; 2.4%), Pipobroman (n=8; 0.6%), Busulphan (n=13; 1.0%), Ruxolitinib (n=11; 0.9%), was similar in the two groups except for aspirin that was used less frequently (p=0.043) in cases (n=320; 74.9%) compared to controls (n=664; 79.9%). In particular, the lower use of aspirin was circumscribed to non-skin solid tumors. A multivariable analysis was carried out in all patients and stratified by different type of tumors (Table). In non-skin solid cancers, the time to exposure of the MPN disease 〉 5 years (OR=2.95; 95% CI 1.54-5.66, p=0.001) and the PV phenotype (OR=2.40, 95% CI 1.15-5.01, p=0.020) were more burdened by the incidence of events than the reference ET group. No difference in SC risk was found for MF patients compared to patients with ET. Interestingly, the independent protective role of aspirin retained its statistical significance only in non-skin SC. In non-melanoma skin cancer, multivariable analysis revealed that the presence of JAK2 mutation was less associated with SC (OR=0.32, 95% CI 0.13-0.81, p=0.016) and confirmed that exposure to HU and other cytotoxic agents was associated with a significantly higher risk of SC (OR=6.00, 95% CI 1.23-29.28, p=0.027 and OR=9.80, 95% CI 1.24-77.78, p=0.031, respectively). This finding was not seen in non-skin SC and in lymphoma. CONCLUSION The considered clinical and biological features, at MPN diagnosis, were not different in cases with SC and controls. During the course of the disease, three factors significantly and independently affected the risk of SC in these MPN patients: 1) patients with PV had a 77% higher risk than those with ET, 2) patients with MPN duration of more than 5 years had a twice higher risk than those with lower duration, 3) for the first time, we documented that in non-skin solid cancers, aspirin treatment reduced SC risk of 38%. Exposure to HU and other cytoreductive drugs was confirmed as a risk factor for non-melanoma skin cancer. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Marchetti:Gilead: Consultancy; takeda: Speakers Bureau; amgen: Speakers Bureau; janssen: Speakers Bureau. Griesshammer:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: INTRODUCTION AND AIMS Almost seventy percent of Acute Myeloid Leukemia (AML) patients will relapse. Fludarabine, Ara-C, Idarrubicine, G-CSF (FLAG-Ida) and FLAG-Ida and Gentuzumab-Ozogamicin (FLAGO-Ida) is frequently used before allogenic stem cell transplant (ASCT). There are several studies analyzing the risk factors for survival in relapsed/refractory patients, but none of them were performed exclusively in patients treated with FLAG-Ida. We analyzed the results of in the Spanish trials conducted by PETHEMA. We also present a predictive score system of survival prognosis based on the data of the patients enrolled METHODS This is a retrospective, multicentre study of the PETHEMA AML epidemiologic Registry. In PETHEMA protocols 98,99,2007,2010 and 2011, FLAG-Ida was included as salvage treatment in patients relapsed or resistant after a 2ndinduction based in 3+7. In PETHEMA trial 2007, FLAG-Ida (or FLAGO-Ida) was administered if complete remission (CR) was not attained in the first induction cycle. The use of FLGO in PETHEMA 2007 trial depended on the availability of GO for each centre. We use overall survival (OS) as final end point of the analysis. Univariate survival analysis was performed by Long-Rank test. Stepwise backward variable selection and Cox proportional hazard multivariable analysis was performed (covariables selected if p

Description: Abstract 1237 Background: The RELMC is a multicentric, 17-hospitals-based cancer registry whose aim is to describe the treatments received by patients with CML, their outcomes, and the variables that influence treatment choices. Aim: To study the response and survival outcomes, in newly diagnosed CML patients treated with Imatinib (Im) as first line treatment. Patients and methods: 249 newly diagnosed CML patients have been included. They are distributed in the following subgroups according to treatments received Im400. 166 patients received only Im400. Result: A summary of response and outcome is included in Table 1. Complete cytogenetic response with regards to the best response, the CCyR rate was lower in patients with Im400-HDIm-2GTKI (60%) and Im400-2GTKI (62%). The rates were 84% in Im400, 83% in Im400-HDIm and 85% in HDIm; P Chi2 8,381(a) p=0,079. The CCyR cumulative incidence was also lower in patients with Im400-HDIm-2GTKI and Im400-2GTKI in comparison to the other groups, although second line response was faster in patients who changed to 2GTKI after Im400. The frequency of CCyR as best response in the Hasford high risk patients was low in all groups (66%,50%,50%,50&55%). Major molecular response MMR as best response was lower in patients with Im400-HDIm-2GTKI (50%) and Im400-2GTKI (47%). The rates were 83%, 81% and 77% in the Im400, Im400-HDIm and HDIm groups respectively; P Chi2 19,4(a)p=0,001. The MMR cumulative incidence was higher in the HDIm group, lower in those treated with Im400-HDIm-2GTKI, and intermediate and similar in the other three groups. MMR as best response in the Hasford high risk patients was also low in all groups (60%, 75%, 50%, 50% & 33%). Complete molecular response regarding best response, the CMR rate was lower in patients with Im400-HDIm-2GTKI (37,5%), Im400-2GTKI (31,6%) and Im400-HDIm (34%). In the other groups, the rate was 48% (Im400), and 72% (HDIm); P Chi2 17,4(a) p=0,002. The CMR cumulative incidence was higher in the HDIm group, and nil in those treated with Im400-HDIm-2GTKI. Salvage therapy after suboptimal response (SR) or Failure (F). Two-thirds of patients with SR or F were able to obtain an optimal response and avoid transformation with a timely therapy change. All but one of the options (Im400-HDIm-2GTKI group) were similarly effective. Survival: 6 patients progressed (2,4%) (4 AP, 2 BC), and died; 6 patients changed to allo BMT and were censored; 6 patients died of non-CML related causes. Conclusion: Disclosures: Palomera: Janssen Cilag: Honoraria. Steegmann:Bristol-Myers Squibb: Honoraria, Participated in advisory boards, Research Funding; Novartis: Participated in advisory boards, Research Funding.

Description: Abstract 3593 Azacitidine (AZA) is currently being used in AML patients (Pts) not deemed candidates for intensive chemotherapy. Most of this usage follows approved drug label by EMA, but off-label usage is not uncommon in Pts with 〉30% bone marrow blast (BMB) cells. Clinical trials are now comparing AZA vs. conventional care in selected populations, and data from daily practice may shed light on the generalizability of their results. A retrospective nationwide study was set up in Spain in order to evaluate the population of AML Pts that is receiving AZA as front-line therapy (Rx) in Spain, its patterns of usage, effectiveness and safety in daily practice conditions, as well as the factors linked to overall response rate (ORR) and overall survival (OS). Only Pts treated before Dec/2010 could be included in this study, that was approved by the Spanish Medicines Agency (AEMPS, code ACL-AZA-2011–01). Data were collected from Oct/2011 to Jan/2012 and analyzed as of Jun/2012. ORR was evaluated according to both ELN-2010 criteria for AML as well as IWG-2006 criteria for MDS (in order to assess the impact of PB changes), OS measured from 1st cycle of AZA to death or last follow-up, and toxicity coded according to NCI CTCAEv3.0. One-hundred and ten untreated Pts (79 M/31 F, median age 75, range 56–89) were recruited from 22 academic and community sites. Comorbidity was present in 96 Pts (cardiac 43, hepatic 10, renal 3, diabetes 26, other neoplasms 18, etc.), ECOG being ≥2 in 33. Thirty Pts had an antecedent hematological disorder. Five cases had recurrent genetic abnormalities (NPM1-mutated AML in 4), 61 had MDS-related AML, 16 therapy-related AML and 28 AML not otherwise specified. Cytogenetics (Cyto) was available in 95 (86.4%): 48 diploid and 47 abnormal. MRC-2010 cyto category was favourable in 1, intermediate in 64 and adverse in 30. Median WBC at Dx was 3.3 x10E9/L (0.8–172.4), WBC before 1st AZA cycle 2.8 (1.0–175.0), platelet count 56 (7–467), PB blast 4.0% (0–100) and hemoglobin 91 g/L (48–142). Sixty-four Pts (58.2%) had BMB〉30% (median 35.0%, range 15.0–98.0%). Median time from Dx to Rx was 19.5 days (0–411). Pts received 745 AZA cycles (median 4, range 1–29; ≥6 cycles 45.4%, ≥12 cycles 18.8%), but 30.9% received ≤2 because of disease progression or toxicity. 7.2% received concomitantly hydroxiurea for WBC control. Route of administration was EV in 5.8%, home administration took place in only 1.5%, and AZA was given as inpatients in 27.3% of the cycles. The no. of days of AZA Rx was 7 in 63.6% of the cycles, week-end off Rx being common place (5–2–2 schedule in 71.9%). Median AZA daily dose was 73.6 mg/sqm (