Abstract: Introduction: The European Leukemia Net (ELN) stratification classifies as favorable prognosis four different subgroups of acute myeloid leukemia (AML) with specific cytogenetic/molecular abnormalities. These forms are potentially curable with standard chemotherapy, even though about 30% of patients (pts) still relapse. Overall survival (OS) of 60% at 5 years is reported but it is not clear if all different subgroups show an homogeneous outcome. The purpose of this study was to assess, in a real life setting, the response rate and the outcome of newly diagnosed AML patients with favorable prognosis based on ELN classification. Data were collected from six hematological centers of the regional network REL (Rete Ematologica Lombarda). Methods: Between 2007 and 2014 we analyzed adult AML patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1(group1), inv(16)(p13q22) or t(16;16)(p13q22)/CBFbeta-MIH11(group 2), normal karyotype and mutated NPM1 and negative FLT3-ITD (group 3) or double mutated CEBPA (CEBPA dm) (group 4). All patients received induction, mainly standard 3+7 chemotherapy (or reduced 1+5 in older pts) in 66% of cases, followed by high dose cytarabine based consolidation in 77% of pts. Clinical and molecular data were analyzed at diagnosis and at different time points during treatment and follow up with qualitative and quantitative PCR. The Kaplan-Meier product-limit method was used to estimate survival curves, and the log-rank test was adopted to evaluate differences between groups of pts. Results: We studied 177 AML pts (96 males and 81 females) with a median age of 55 years (range 20-80): 27 of group 1, 35 of group 2, 98 of group 3 and 17 of group 4. Complete hematological response (CHR), assessed in 176 pts, was achieved in 161 pts (92%): 23(85%), 32(91%), 90(93%), 16(94%) respectively in group 1, 2, 3, 4 without significant difference (p=0.26). Molecular complete remission (mCR), evaluated in 152 pts out of 161 in CHR, was documented in 102 pts. Forty pts entered mCR after induction and 62 pts at the end of consolidation or later (1-40 months); therefore, mCR rate was 67%. Considering the type of the method, 48 pts resulted in mCR with qualitative PCR, the remaining 54 (53%) with qualitatitive and quantitative PCR. Median time to mCR was 4 months and was different among groups (p=0.03); in particular, t(8;21) pts obtained mCR later than NPM1 pts (8 versus 2.6 months) (p=0.01). The relapse rate was 41% and the median time to relapse was 10.2 months, without any difference among groups (respectively p=0.5 and p=0.8). Five years overall survival (OS) and disease free survival (DFS) were 65% and 47% with no significant difference among groups (respectively p=0.3 and p=0.9). Age ( 〈 60 years) was the only parameter that affected OS (80% versus 41%, p 〈 0.001) and DFS (56% versus 33%, p=0.038). In a time-dependent analysis there is a significant association between mCR and DFS, therefore, if mCR was reached the risk of relapse decreased of 60% (p 〈 0.001). Moreover, if qualitative mCR was confirmed by quantitative analysis, 5 years-DFS was much higher (78%). Conclusion: This study, conducted in a non selected population of favorable risk AML patients, confirms high CR rate and the prognostic value of age, favoring patients younger than 60 years. Our data confirm that the ELN classification identifies a clinically homogeneous group of good risk AML patients sharing comparable outcome even outside clinical trials setting. Molecular complete remission is associated with better outcome, in particular when assessed by quantitative PCR. Disclosures No relevant conflicts of interest to declare.

Abstract: Among patients who have chronic myeloid leukemia and receive treatment with tyrosine kinase inhibitors, the likelihood of obtaining a sustained deep molecular response and a durable treatment‐free remission is lower in those who have the e13a2 BCR‐ABL transcript. After 5 years of treatment, the probability that patients with the e13a2 transcript will achieve a sustained deep molecular response is 17.4% with imatinib and 36.2% with second‐generation tyrosine kinase inhibitors.

Abstract: The efficacy of posaconazole prophylaxis against invasive fungal infection (IFI) in acute myeloid leukemia (AML) patients during induction therapy has been demonstrated both in randomized and real-life studies. Absorption of posaconazole is enhanced by food intake, which may be impaired by gastrointestinal mucositis. However, correlation between posaconazole serum levels and breakthrough IFI has not been clearly demonstrated and the usefulness of therapeutic drug monitoring (TDM) is still a matter of debate. Aims In order to clarify the role of posaconazole TDM in preventing opportunistic infections, we correlated posaconazole serum levels with the incidence of breakthrough proven/probable IFI and the need for empiric/pre-emptive/targeted antifungal therapy among AML induction patients. A comparative analysis with an historical cohort receiving mainly itraconazole prophylaxis was also performed. Patients and Methods Since June 2004 a program of active epidemiological surveillance is ongoing at our Institute. Posaconazole prophylaxis was routinely introduced among AML induction patients on July 2011; data concerning incidence of IFI during AML induction were extracted from two consecutive periods (Jul2009-Jun2011 and Jul2011-Jun2013). Patients received posaconazole at 200 mg three times a day; 1st serum posaconazole level was determined on day 7 and repeated every 7 days. A serum level ≥500 ng/mL was considered adequate. Serum galactomannan (GM) was monitored two times a week; thorax CT scan was performed within 3 days from the onset of fever. Systemic antifungal therapy was started empirically, in the case of persistent fever, with or without radiological signs of fungal infections. Results Overall, 120 AML patients were evaluated, 60 in both periods. The two cohorts did not differ in median age, M/F ratio and type of treatment. During the 1st period 9/60 (15%) breakthrough IFI (2 candidemia, 7 aspergillosis) were observed, as compared to 2/60 (3.3%) in the 2nd period (1 candidemia and 1 aspergillosis), p=0.027 (Chi-square test). In all but one cases of aspergillosis, GM positivity was the microbiological criterion to meet the diagnosis of probable/proven IFI. The need for systemic antifungal therapy was similar in both periods (40% and 38.3%, respectively). Posaconazole serum levels was available in 50/60 patients (83%) during the 2nd period. Mean serum concentration did not change significantly over time (mean value±SE: 551±48.7 543±64, 643±107.4, 698±164.7 at 1st, 2nd, 3rd, 4th week of therapy respectively, p=0.64). Adequate serum levels throughout the induction period were maintained in 19 cases (38%). None of them developed IFI. Posaconazole serum level was below the therapeutic threshold in the patient developing candidemia and not evaluable in the one who developed pulmonary aspergillosis 3 days after starting posaconazole prophylaxis. Systemic antifungal therapy, was given to 4/19 (21.1%) patients with persistently adequate posaconazole serum levels as compared to 13/31 (41.3%) patients with at least 1 posaconazole serum level below the therapeutic threshold (p=0.13). Conclusions Our study confirms that posaconazole prophylaxis significantly reduces the incidence of proven/probable breakthrough IFI, particularly aspergillosis, in a “real life” setting. No patient with persistently adequate posaconazole serum levels developed IFI. In this subgroup the need for systemic antifungal therapy was halved compared to patients with below-target posaconazole serum levels. Weather the reduced sensitivity of diagnostic biomarker tests due to azole prophylaxis may contribute to underestimate a diagnosis of IFI remains an open question. Disclosures: No relevant conflicts of interest to declare.

Abstract: Abstract 4101 Background and aim The only curative option for adult patients with refractory or relapsed ALL is allogeneic haematopoietic stem cell transplant (allo-HSCT), which can offer a 28-34% long term survival in transplanted patients. However the actual feasibility of allo-HSCT is only 20-30% in unselected patients because of the low rate (30-50%) of complete remission (CR) achieved with salvage regimens (Tavernier, 2007- Thomas, 1999), the high rate of early relapse (Martino, 1999) and the difficulties in finding a suitable donor before progression (Davies, 1996). Hence, relapsed ALL can be actually cured in less than 10% of unselected adult patients. Using a second line treatment capable of obtaining a higher proportion of CR of longer duration may improve the dismal overall prognosis of patients. We report on the efficacy and toxicity profile of the combination of 6-metilprednisolone, mitoxantrone, etoposide and high-dose cytarabine (MECp), a salvage regimen containing cytostatic drugs to which patients had not been exposed during first line therapy, except for cytarabine at lower doses. Patients and Methods Between October 2000 and May 2009, 18 refractory/relapsed ALL patients were treated at our Institution with MECp regimen, consisting of a single course of etoposide 80mg/mq/die iv, cytarabine 1000mg/mq/die iv for 6 hours and mitoxantrone 6mg/mq/die iv 9 hours after cytarabine infusion for 6 days associated to metilprednisolone 50 mg/mq/die for 21 days, subsequently tapered to zero over one week. Three patients received an experimental sequential pulsed chemotherapy program in a multiinstitutional setting. At diagnosis, all patients had been treated according to the NILG-ALL 00/09 program (Bassan, Blood 2009). Four had been refractory to induction therapy and 14 had relapsed after a median of 12 months (range 3-43), 11 while on consolidation/maintenance, one after allo-HSCT, two after 3 and 12 months from the end of maintenance. There were 10 males and 8 females with a median age of 28 (range 17-64). ALL lineage was B in 9 cases (4 pro-B, 4 common, 1 pre B), T in 8 (5 pro-T, 3 cortical-TIII) and biphenotypic in 1. Molecular studies showed MLL/AF4 rearrangement in 3 and bcr/abl rearrangement in 3 cases, all before tyrosine-kinase inhibitors were available. Karyotypic abnormalities were present in 10 of 16 evaluable cases. Patients were treated in single/double bed rooms with reverse isolation. In 3 cases treatment duration was reduced to 4 days. Results CR was obtained in 13 of 18 patient (72,2%), independently of immunophenotype and time to relapse. CR rate was 100% in all ten patients with karyotypic abnormalities. Three patients (16%) died in aplasia during treatment, 2 of septic shock and 1 of unexplained shock. Two patients (T-ALL) were resistant. Recovery of neutrophils ( 〉 0,5×109/L) and platelets ( 〉 20×109/L) required a median of 22 days (range 17-37) and 28 days (range 21-45) from the start of therapy, respectively. Infections were documented in 9 of 18 (50%), being fatal in 2 (11%). Non-haematologic toxicity, mainly mucositis, was negligible. The median duration of CR was 5 months (range 2-5) which allowed 9 of 13 CR patients (69%) to undergo allo-HSCT (7 MUD, 1 HLA-identical sibling and 1 cord blood) after a median of 4 months (range 2-7) from CR. Reason for not being transplanted was failure of donor search in 4 patients who relapsed a median of 4 months. Causes of death included progressive disease in 7 patients, in 3 cases after HSCT, and transplant-related toxicity in 3 patients. The median survival of patients achieving CR was 13 months (range 7-33) and overall survival of the entire cohort was 8 months (range 1-33m). Conclusions With MECp, a combination of drugs not used during previous first-line therapy, a higher CR rate (72%) than commonly reported could be obtained, with acceptable toxicity. CR duration was long enough to allow 44,4% of patients to receive a non-family donor allo-HSCT, which is presently the best, yet still unsatisfactory, treatment option for adult patients with refractory/relapsed ALL. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction: Postremission treatment in adult acute myeloid leukemia (AML) is mandatory to improve long-term remission duration. Allogeneic stem-cell transplantation (allo-SCT) is considered gold standard in younger patients (pts) with higher risk of relapse, whereas in pts categorized as standard-risk (SR) AML the optimal treatment remains an open issue. High-dose cytarabine (HD-ARAC) is considered the backbone of postremission treatment in SR AML. The optimal dose and schedule, and the clinical benefit of additional chemotherapeutic agents remain controversial (Schaich, 2011- Lowenberg, 2011- Lowenberg, 2013) as well as the relative efficacy of HD-ARAC in the different cytogenetic and molecular subgroups of SR AML. We analyzed the very long term outcome of consecutive unselected AML pts treated according to AML 00 NILG protocol (Bassan, Blood, 2003: 102; 11) with three repetitive HD-ARAC-based cycles, associated with idarubicin, followed by limited peripheral blood stem cell (PBSC) support, in order to reduce toxicities. Methods: We evaluated 263 consecutive AML pts, diagnosed at our Institution, from January 2001 to March 2016 (median age 52 years - range 15-65). The treatment plan included induction with ICE (Idarubicin-Cytarabine-Etoposide) followed by IC consolidation or HD-ARAC/HD-idarubicin (SPLIT therapy) in refractory cases. ARAC 1g/mq bd for 4 days (A8) was given to CR pts, to collect 3-6x10^6 CD34/kg in 3 aliquots. Patients with ELN favorable or intermediate risk AML, considered SR AML, received 3 cycles of HD-ARAC (2g/mq bd for 5 days) plus idarubicin (8mg/mq for 2 days) with PBSC reinfusion (1-2x10^6 CD34/Kg) (A20). The pts with insufficient CD34 cells yield, received 2 courses HD-ARAC (1g/mq bd for 5 days) plus idarubicin (10mg/mq day 1) (A10). The cumulative dose of ARAC and idarubicin given according to A20 protocol were 69,4 g/mq and 162 mg/mq, respectively. Results: Among 263 pts, 142 (54%) pts were considered SR and 116 (44.1%) HR. Only 5 pts were lacking molecular or cytogenetic information (1.9%) to allow ELN risk classification. Accordingly, 65 pts (25.2%) were favorable [35.4% core binding factor (CBF) positive, 9.2% CEPBA mutated and 55.4% NPM mutated], 87 (33.7%) Intermediate-I, 45 (17.4%) Intermediate II and 61 (23.7%) adverse risk. CR rate after ICE treatment was 77.6% (204/263), 95.8% in SR and 56% in HR pts and after ICE+SPLIT it was 88.2% (232/263); early or aplastic death was 6%. A8 course was administered in 218 pts, of whom 179 were successfully mobilized (82.1%). Among 136 SR pts, 127 were received HD-ARAC (A20 or A10), 4 allo-SCT for early relapse, 3 pts did not proceed to A20 because of prolonged cytopenia and 2 are ongoing. Hematological toxicity was acceptable. ANC recovered at a median of 10 days after CD34+ cells reinfusion. Two death in CR occurred within 100 days after A20 therapy (1.6%). After a median follow-up of 53.3 months (range 1-172), the median survival of SR AML patients was 118.9 months, the DFS and OS at 5 y were 51+/-4.8% and 56.5+/-4.7%, and at 10 y 43.3+/-5.9% and 49.6+/-5.7%, respectively. According to ELN risk, the OS at 5 y and 10 y was 78.3+/-6% and 68+/-8.7% in favorable (median OS not reached), 52.3+/-8% and 46+/-9.4% in Intermediate-I (median OS 118.8 months), and 42+10% and 33.6+/-10.9% in Intermediate-II (median OS 33.1 months) (p0.0034) (Figure1). According to molecular characteristics, the OS at 5-y was 100% in CEBPA-mutated, 77+/-9% (+/-SE) in CBF-mutated and 71+/-11% in NPM-mutated subgroups, respectively (Figure 2). In NPM-mutated pts it was 56+/-14% if FLT3 was mutated and 75+/-10% if not. At 8-y OS was not evaluable in CEBPA-mutated, it remained 77+/-9% in CBF mutated but dropped to 47+/-15% in NPM-mutated pts due to late relapses (28%), which occurred in pts without FLT3. The median time to relapse in NPM pts was 17 m, the latest relapse occurred after 97 months. Conclusion: A postremission program with repeated courses of HD-ARAC associated to idarubicin and limited autologous CD34+ cells support was feasible, well tolerated and very effective, also long-term, in pts with ELN favourable or intermediate risk AML. The late relapse tendency of NPM-mutated AML is puzzling and should be considered by innovative programs aimed at improving these results. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction: Acute Myeloid Leukemia (AML) is a heterogeneous disorder characterized by a wide range of cytogenetic and molecular aberrations, that affect prognosis and guide treatment decisions. However there is a still large group of patients (pts) considered at intermediate risk whose outcome needs to be better defined. Next-generation sequencing (NGS) can simultaneously detect various mutations, leading to better define its prognostic profile. The role of some mutations, including isocitrate dehydrogenase (IDH) mutations (IDHm), is still controversial. Aim: We evaluated by NGS monitoring at different time points the prognostic role of IDH1/2m in AML pts with normal karyotype, both in the subgroup with mutations of NPM1 (NPM1m) or FLT3 (FLT3m) and in the subgroup without detectable mutations (wt-AML). Methods: Using Sophia Myeloid Solution kit (SOPHiA Genetics), we performed targeted NGS, covering 30 gene regions, in 104 bone marrow samples collected at diagnosis (53), after first consolidation (30) and at relapse (21), in 53 pts (M/F: 24/29; median age: 56 y, range 22-74), treated according to NILG-AML00 protocol (NCT00400673). Standard PCR to detect NPM1m and FLT3m was performed and we identified 20 NPM1m, 3 NPM1+FLT3-ITDm, 4 FLT3-ITDm and 26 wt-AML. Results: At diagnosis, among 219 pathogenic mutations detected, IDHm represented 10.5% of them (median VAF: 39.1%; range 6.2-49.6%). IDHm was observed in 23/53 pts (43.4%) (IDH1m in 11 and IDH2m in 12). In these pts , more frequently commutated genes were DNMT3A (28%), NPM1 (13%), FLT3-ITD/TKD (14%), ASXL1 (6%), SRSF2 and NRAS (9% each). Complete remission (CR) was achieved in 49/53 (92.5%) pts without difference in response rate according to IDH status (86% in IDHm vs 94% in IDH wild-type, wt). Relapse occurred in 28/49 (57%) pts after a median of 11 months (mo), range 2-61. The frequency of relapse was not significantly different across all types of mutations identified, except for IDH2m which was associated with a higher risk of relapse (10/11 in IDH2m vs 18/38 in IDH2wt; p: 0.014), without differences between R172K and R140Q. On the contrary, IDH1m, present in 18% of relapsed pts, did not impact on relapse (5/10 vs 23/39, p: 0.7). Particularly, in the wt-AML group, the IDH2m was prevalent in pts developing relapse (6/11, 54.5%) and all pts with IDH2m relapsed, with median of 13 mo, range 6-24 (6/6 in IDH2m vs 5/17 in IDH2wt, p:0.0046). Among the co-occurrence mutations, the IDH2/DNMT3A was associated with higher relapse risk (9/9 vs 19/40; p: 0.0063). DNMT3A associated with other mutations did not impact on relapse risk. At a median follow-up of 23 mo, median relapse free survival (RFS) and overall survival (OS) of whole population were 24 and 53 mo, respectively. The IDH2m impacted on OS: 23.5 mo in IDH2m vs 72 in IDH2wt pts (p:0.0093) (Fig 1a), but not in RFS (13 vs 29 mo in IDH2m and IDH2wt, respectively (p:0.1). Considering the subgroups of wt-AML, the RFS (Fig. 1b) and OS were 13 and 23.5 mo in IDH2m vs undefined in IDH2-wt (p:0.0014 and p:0.1), respectively. In pts with NPM1 or FLT3m, RFS and OS were 9 and 53 mo in IDH2m vs 29 and 73 mo in IDH2-wt (p:0.2 and p:0.15), respectively. We did not find the other genomic pattern predicting relapse in this group. After consolidation, NGS monitoring was performed in 30 pts in CR. Of the 13 IDH AML pts evaluated, no mutations was observed in 4 (28.5%); the persistence of IDHm was not associated with a significantly higher relapse (p:0.5). Among other mutations present at diagnosis, NGS clearance after consolidation occurred in pts with NRAS, KRAS, PTPN11 and FLT3-ITD/TKD. Conversely, it was limited for the following mutations: TET2 (8/11), DNMT3A (7/13), SRSF2 (6/6), IDH2 (4/5), ASXL1 (2/2), IDH1 (2/4) and NPM1 (1/12). Overall, the persistence of any type of gene mutations after consolidation was predictive of relapse (2/9 vs 6/7, p:0.04), only in wt-AML subgroup. At relapse, of the 11 IDHm pts analyzed, 7/7 IDH2m and 3/4 IDH1m showed the reappearance of mutations. Conclusion: In this retrospective monocentric study, the presence at diagnosis of IDH2m correlated with relapse risk and with survival, suggesting that additional treatment with targeted agents and or consolidation with allogeneic transplant should be considered. In addition, in AML without NPM1m or FLT3m, the persistence of genes mutation detected by NGS monitoring after consolidation had a significant prognostic value to predict subsequent relapse. Figure 1 Figure 1. Disclosures Borlenghi: Amgen, Janssen: Consultancy. Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: Gentili: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Abstract: BACKGROUND Tyrosine Kinase Inhibitor (TKIs) discontinuation has become, nowadays, under proper conditions, a feasible option for chronic myeloid leukemia (CML) also in "real life" setting. Different papers investigated which factors (age, sex, type of TKI, previous r-interferonα -r-INFα- therapy, line of therapy at stop, type of transcript, duration of TKI therapy and of sustained deep molecular response -sDMR-, Sokal risk score) could predict a successful TKIs discontinuation either within protocols or outside of clinical trials, and the results are not unique. AIM We retrospectively evaluated our CML pts who stopped TKI after sDMR in order to assess the variables that could influence the probability of a durable TFR. METHODS BCR-ABL transcripts were determined by RQ-PCR performed according to EAC protocol (Gabert et al, 2003) and to the standards of the Italian National Network Labnet. Criteria for TKI discontinuation was sustained DMR (MR4 or better) for at least 2 years. After TKI withdrawal, RQ-PCR for BCR-ABL was performed every month during the first year and every 2 months thereafter. TKI treatment was reintroduced if DMR loss occurred.TFR was assessed using the Kaplan-Meier method; potential prognostic factors were considered for multivariable analyses at a level less than .20. RESULTS Between October 2010 and January 2019, 68 patients discontinued TKIs, 18 of them after less than 5 years of treatment because of pregnancy desire (3), intolerance (6), patient's desire/non compliance (5), enrollment in study protocols (4). At discontinuation median age was 63 years (30-85), median time from TKI start 85 months (30-190), median duration of sustained DMR 48 months (24-153). Sokal distribution was 48%, 31% and 18% for low, intermediate and high risk respectively (2 patient was not evaluable). E14a2 transcript type was present in 52 pts and e13a2 in 16 pts. Thirty-eight patients stopped imatinib, 25 nilotinib (19 in 1st line, 6 in 2nd line), 5 dasatinib. Before imatinib 15 patients received r-IFNα, for a median time of 60 months (3-256). Median follow up after TKI stop was 39 months (5-105, 〉 24 in 61, 〈 12 in only 2 patients). Twenty-eight (41%) patients lost DMR. Median time off-therapy for these patients was 3 months (1-19), only 2 lost DMR after 6 months (at +16 and +19 months). One patient aged 87 years has not yet resumed therapy but remains in stable MR3 at 34 months after TKI discontinuation. Therapy was restarted in 27 patients (1 in MR1, 11 in MR2, 15 in MR3), 24 achieved a second DMR after a median interval of 2 months (1-18); 3/27 patients are in M3 after 2, 22 and 26 months. Neither cytogenetic relapses, nor progressions were documented. One patient died in DMR for pancreatic cancer. Univariate analysis showed no difference in relapse risk according to age, gender, type of TKI (imatinib vs 2nd generation TKIs), and Sokal score, while the e14a2 vs e13a2 transcript type (p = 0.011), duration of TKI therapy 〉 60 months (p = 0.025) and previous r-IFNα therapy (p=0.021) were significantly linked to better outcome after TKI discontinuation; sDMR 〉 72 months is very close to be a significant variable (p=0.055). At multivariate analysis only the type of BCR-ABL transcript (p=0.027) and previous r-IFNα ( p=0.016) remained independent significant prognostic factors -figure A and figure B-. CONCLUSION e14a2 transcript type was confirmed as a robust favorable prognostic factor for TFR maintenance. In our experience, 2GTKIs didn't impact favorably TFR duration after TKIs discontinuation, conversely r-IFNα treatment before TKI improved the probability of maintaining DMR after TKI withdrawal, particularly in e13a2 patients. In fact r-IFNα before imatinib reversed the negative prognostic impact on TFR maintenance of the e13a2 transcript type. Disclosures D'Adda: Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rossi:Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Daiichi-Sankyo: Consultancy.