Complete Molecular Risk Stratification of De Novo Acute Myeloid Leukemia with Intermediate Cytogenetics Using an Eight-Gene Panel

Abstract Background: Refining risk stratification of acute myeloid leukemia (AML) using molecular profiling, especially those with intermediate cytogentic risk, is becoming standard of care. However, current WHO and ELN classifications are focused on few markers, mainly FLT3, NPM1, and CEBPA. While these abnormalities are relatively common, not all patients with AML and intermediate or normal cytogenetics will have abnormalities in these genes leaving large percentage of patients without refined risk stratification. We demonstrate that using 8 different AML-related genes are adequate to provide one or more molecular markers to further risk stratify patients with de novo AML. Method: Using direct sequencing we analyzed 211 samples referred from community practice with the diagnosis AML for molecular analysis. All samples were evaluated prospectively for mutations in FLT3, NPM1, IDH1, IDH2, CEBPA, WT1, RUNX1, and TP53 using direct sequencing. Fragment length analysis was used in addition to sequencing for FLT3 and NPM1. Available morphology, cytogenetics, and clinical data along with history were reviewed. Results: Of the 211 samples tested 103 (49%) had at least one or more molecular abnormality adequate for refining the risk classification. The mutations detected in these 103 patients were as follows: 27 (26%) FLT-ITD, 10 (10%) FLT3-TKD, 30 (29%) NPM1, 7 (7%) CEBPA, 14 (14%) IDH1, 13 (13%) IDH2, 10 (10%) WT1, 38 (37%) RUNX1, and 2 (2%) TP53. There was significant overlap and most patients had more than one mutation as illustrated in the graph below. However, if the testing was restricted to FLT3, NPM1, CEBPA and DNMT3A, only 56 (54%) would have had refined risk classification and 46% of patients would have remained without subclassification. The most striking finding was that all the remaining patients, who had no molecular abnormality detected in any of these 8 genes, had either history of MDS evolved to AML, therapy-related AML, or cytogenetic abnormalities other than intermediate (multiplex cytogenetic abnormalities or core-binding factor abnormality). Conclusion: Using FLT3, NPM1, CEBPA, and DNMT3A is inadequate for the molecular characterization of patients with AML. Patients with de novo AML and intermediate risk cytogenetics can be adequately prognostically subclassified and molecularly studied by testing only 8 genes. More importantly, this data confirms that the molecular biology driving de novo AML is significantly different from that driving MDS, AML with myelodysplasia-related changes, therapy-related AML, or AML with core binding factor or multiplex cytogenetics. Unlike de novo AML, these entities should be molecularly studied using MDS-specific driver genes. Furthermore, this data suggests that different therapeutic approaches should be developed for MDS and MDS-related AML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Adverse Prognostic Significance of KIT Mutations in Adult Acute Myeloid Leukemia With inv(16) and t(8;21): A Cancer and Leukemia Group B Study

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.9500 ◽

2006 ◽

Vol 24 (24) ◽

pp. 3904-3911 ◽

Cited By ~ 448

Author(s):

Peter Paschka ◽

Guido Marcucci ◽

Amy S. Ruppert ◽

Krzysztof Mrózek ◽

Hankui Chen ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Direct Sequencing ◽

Prognostic Significance ◽

Prognostic Impact ◽

Core Binding Factor ◽

Relapse Risk ◽

Binding Factor ◽

Acute Myeloid

Purpose To analyze the prognostic impact of mutated KIT (mutKIT) in core-binding factor acute myeloid leukemia (AML) with inv(16)(p13q22) and t(8;21)(q22;q22). Patients and Methods Sixty-one adults with inv(16) and 49 adults with t(8;21), assigned to postremission therapy with repetitive cycles of higher dose cytarabine were analyzed for mutKIT in exon 17 (mutKIT17) and 8 (mutKIT8) by denaturing high-performance liquid chromatography and direct sequencing at diagnosis. The median follow-up was 5.3 years. Results Among patients with inv(16), 29.5% had mutKIT (16% with mutKIT17 and 13% with sole mutKIT8). Among patients with t(8;21), 22% had mutKIT (18% with mutKIT17 and 4% with sole mutKIT8). Complete remission rates of patients with mutKIT and wild-type KIT (wtKIT) were similar in both cytogenetic groups. In inv(16), the cumulative incidence of relapse (CIR) was higher for patients with mutKIT (P = .05; 5-year CIR, 56% v 29%) and those with mutKIT17 (P = .002; 5-year CIR, 80% v 29%) compared with wtKIT patients. Once data were adjusted for sex, mutKIT predicted worse overall survival (OS). In t(8;21), mutKIT predicted higher CIR (P = .017; 5-year CIR, 70% v 36%), but did not influence OS. Conclusion We report for the first time that mutKIT, and particularly mutKIT17, confer higher relapse risk, and both mutKIT17 and mutKIT8 appear to adversely affect OS in AML with inv(16). We also confirm the adverse impact of mutKIT on relapse risk in t(8;21) AML. We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors.

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FLT3, NPM1 and MLL Mutations Help Risk Stratification in Pediatric Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v114.22.1574.1574 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1574-1574

Author(s):

Shuhong Shen ◽

Yin Liu ◽

JingYan Tang ◽

Long-Jun Gu

Keyword(s):

Acute Myeloid Leukemia ◽

Risk Stratification ◽

Myeloid Leukemia ◽

Tandem Duplication ◽

De Novo ◽

Genetic Alterations ◽

Npm1 Mutation ◽

De Novo Aml ◽

Pediatric Aml ◽

Acute Myeloid

Abstract Abstract 1574 Poster Board I-600 Introduction Acute myeloid leukemia (AML) is a heterogeneous disease which harbors various genetic alterations. Among theses genetic events, Mutations of FLT3, NPM1, MLL and other genes often predict prognosis, particularly in cases cytogenetic normal (CN-AML). Could these be criteria for risk stratification in Pediatric AML ? Patients and Methods 155 cases of de novo AML were diagnosed routinely according to morphology, immunology, cytogenetics, and molecular biology examination on bone marrow (BM) aspirates between Jan. 2002 and Dec. 2008. All patients received chemotherapy according to the AML-XH-99 protocol, which consist of Daunorubicin, Cytosine arabinoside, Etoposide, Homoharringtonine. For acute promyelocytic leukemia, all-trans retinoic acid and Arsenic trioxide were also included. Meanwhile, total RNA of leukemic cells form all diagnostic BM samples were extracted, and then reverse transcribed. MLL partial tandem duplication (MLL/PTD) fusion transcripts were screened by real-time quantitative polymerase chain reaction. FLT3 internal tandem duplication (FLT3/ITD), FLT3 tyrosine kinase domain mutation (FLT3/TKD) and NPM1 mutation were examined by High resolution melting analysis. Results Of the 155 children with de novo AML, 121(78.1%) had received chemotherapy for more than one week with data available for analysis. Among them, 55(45.5%) was cytogenetically normal (CN-AML). In this total cohort of patients 49(27.09%) had FLT3/ITD (32.70% in CN-AML), 14 (9.03%) had FLT3/TKD (7.30% in CN-AML), 62 (40%) had NPM1 mutation (49% in CN-AML), and additional 8 (5.16%) had MLL/PTD (5.50% in CN-AML). In this cohort of patients 98 (63.22%) had at least one mutation. The clinical outcomes were listed in table 1. Generally, patients with FLT3 mutation (ITD or TKD mutation) usually have worse results after chemotherapy, as reported previously by other researchers. Meanwhile, NPM1 mutations usually predict better prognosis in our cohort of AML patients. MLL/PTD always predicts the worst outcome in AML as other MLL rearrangements in leukemia. Among CN-AML patients, 5-year EFS and OS were similar to whole cohort of patients according to those mutations. Cox regression analysis in a univariate model revealed that the presence of FLT3/ITD and NPM1 was significant prognostic factor of EFS, (P<0.05). We therefore proposed a molecular-risk classification of pediatric AML patients based on the data we got in this study. For the newly classified groups of low, medium and high risk groups, EFS rate was 62.03%±8.42%, 45.42%±4.52%, and 14.85%±2.99%, respectively, P=0.00. CRD for the 3 groups was 27.69±21.34 months, 22.62±19.64 months, 13.26±11.95 months, respectively, p=.022. Our results indicate that combinations of these couple of molecular events may be the useful tool for further classify AML in children. Disclosures No relevant conflicts of interest to declare.

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Comparison of therapy‐related and de novo core binding factor acute myeloid leukemia: A bone marrow pathology group study

American Journal of Hematology ◽

10.1002/ajh.25814 ◽

2020 ◽

Vol 95 (7) ◽

pp. 799-808 ◽

Cited By ~ 1

Author(s):

Heesun J. Rogers ◽

Xiaoqiong Wang ◽

Yan Xie ◽

Adam R. Davis ◽

Beenu Thakral ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Core Binding Factor ◽

Binding Factor ◽

Acute Myeloid

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Incidence and Clinical Features of Core Binding Factor Acute Myeloid Leukemia: A Collaborative Study of the Japan Adult Leukemia Study Group and the Korean Society of Hematology.

Blood ◽

10.1182/blood.v120.21.2584.2584 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2584-2584

Author(s):

Tomohiko Taki ◽

Hee-Je Kim ◽

Shigeki Ohtake ◽

Byung-Sik Cho ◽

Hitoshi Kiyoi ◽

...

Keyword(s):

Myeloid Leukemia ◽

De Novo ◽

Chromosome Abnormalities ◽

Study Group ◽

Core Binding Factor ◽

Binding Factor ◽

Additional Chromosome ◽

De Novo Aml ◽

Adult Leukemia ◽

Acute Myeloid

Abstract Abstract 2584 Background: Core binding factor (CBF) acute myeloid leukemia (AML) is a specific subgroup of AML, which is commonly related with rearrangements of genes encoding subunits of CBF, AML1 /RUNX1 (AML1-ETO) in t(8;21)(q22;q22) or CBFB (CBFB-MYH11) in inv(16)(p13q22)/t(16;16)(p13;q22), and both clinical outcomes are usually superior in de novo AML. According to literatures, the frequency of patients with t(8;21)(q22;q22) among AML is higher in Japan and Korea than Western countries. However, the accurate incidence and clinical features of CBF-AML are unclear in a large cohort. Patients and methods: We have analyzed 1,536 de novo AML patients from 2 clinical trials of Japan Adult Leukemia Study Group (JALSG, AML97 and AML201 studies, registered from December 1997 to December 2005) and 876 from 3 institutes in Korea (diagnosed from January 2007 to December 2011). Patients from 15 to 64 years old were included in this study, but those with FAB-M3/t(15;17)(q22;q12–21) were excluded. Results: The incidence of CBF-AML was similar in both Japan and Korea (23.3% and 21.2%, P=0.2), however, that of t(8;21) and inv(16) each was a little different between both countries. t(8;21) and inv(16) were observed in 18.6% and 4.9% in Japan, and in 15.0% and 6.3% in Korea, respectively. Of these, the incidence of t(8;21) in Korea was lower than that in Japan (P=0.02), but higher than those reported from Western countries [4.9–8.6% in MRC, CALGB, and SWOG/ECOG except t(15;17), P<0.001]. The prognoses of patients with t(8;21) and inv(16) were similar in complete remission (CR) rate between both countries, but different in 5-year overall survival (OS) and disease-free survival (DFS) rates. CR rate was 91.3% (Japan) and 93.9% (Korea) in t(8;21) (p=0.3), and 98.7% and 100% in inv(16) (P=0.6), respectively. In t(8;21), OS was relatively better in Japan than in Korea (64.6% versus 54.9%, P=0.055), however, DFS tended to be worse in Japan than in Korea (47.6% versus 56.1%, P=0.47). In inv(16), almost the same results with t(8;21) were observed (72.6% versus 65.7% in OS, P=0.2, and 47.7% versus 62.2% in DFS, P=0.06). The white blood cell (WBC) counts and WBC index were prognostic factors in patients with t(8;21), and significantly related to clinical outcome in Japanese patients, however, no significant differences were observed in Korean patients. Patients with t(8;21) having high WBC count (>=10×109/L) were found to have a poor outcome in Japan (44.8% versus 74.5% in OS and 32.4% versus 57.5% in DFS; P<0.001 each), but not in Korea (53.0% versus 57.1% in OS, P=0.8, and 54.0% versus 58.2% in DFS; P=0.6). Additional chromosome abnormalities found in t(8;21) and inv(16) were similar in both countries. In t(8;21), a sole t(8;21) was observed in 25.5% and 25.2%, a loss of a sex chromosome (-X/-Y) in 60.8% and 60.3%, del(9q) in 8.4% and 6.1%, and other abnormalities including 7q- in 23.8% and 29.0% in Japan and Korea, respectively. However, correlations of additional chromosome abnormalities and clinical outcome were different in each country. In Japan, patients with -X/-Y had relatively favorable OS than those with sole t(8;21) [69.1% versus 57.5%, P=0.08]. However, opposite correlation was observed in Korea [48.1% in -X/-Y versus 59.6% in sole t(8;21), P=0.03], although sole t(8;21) had identical OS in both counties [57.5% versus 59.6%, P=0.4] Conclusions: High incidence of t(8;21) in AML was observed in both countries, however, prognostic significance of various factors, such as WBC counts, WBC index, and additional chromosome abnormalities, were different in each country. One of the reasons for these differences may be dependent on the different treatment protocols in each country, and further analysis of factors associated with prognosis in each country is needed. Disclosures: No relevant conflicts of interest to declare.

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PB1776 REAL WORLD DATA OF CLINICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF ADULT PATIENTS WITH DE NOVO CORE-BINDING FACTOR ACUTE MYELOID LEUKEMIA

HemaSphere ◽

10.1097/01.hs9.0000565612.86445.02 ◽

2019 ◽

Vol 3 (S1) ◽

pp. 815

Author(s):

S.P. Mirgh ◽

J. Kapoor ◽

A. Garg ◽

V. Khushoo ◽

B. Mohan ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Treatment Outcomes ◽

Real World ◽

Myeloid Leukemia ◽

Clinical Characteristics ◽

De Novo ◽

Real World Data ◽

Core Binding Factor ◽

Binding Factor ◽

Acute Myeloid

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Excess Reduction of Anthracyclines Results in Inferior Event-Free Survival in Core Binding Factor Acute Myeloid Leukemia in Children; A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)

Blood ◽

10.1182/blood.v120.21.409.409 ◽

2012 ◽

Vol 120 (21) ◽

pp. 409-409 ◽

Cited By ~ 1

Author(s):

Daisuke Tomizawa ◽

Akio Tawa ◽

Tomoyuki Watanabe ◽

Akiko Moriya Saito ◽

Kazuko Kudo ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Risk Stratification ◽

Cumulative Dose ◽

Myeloid Leukemia ◽

Event Free Survival ◽

Core Binding Factor ◽

Free Survival ◽

Binding Factor ◽

Intensive Use ◽

Acute Myeloid

Abstract Abstract 409 Background: Intensive combination chemotherapy of Ara-C and anthracyclines, together with optimal risk stratification, led to 70% probability of survival (pOS) in childhood acute myeloid leukemia (AML) nowadays. Therefore, one of the main subjects for AML chemotherapy in children is to reduce anthracyclines to avoid late cardiotoxicity which could occur in lower cumulative dose compared to adults. High-dose (HD) Ara-C has contributed to improved survival especially in core binding factor (CBF)-AML, and we hypothesized that the intensive use of HD Ara-C could compensate for reduction of anthracycline dose in children with CBF-AML. Patients & Methods: JPLSG AML-05, registered at http://www.umin.ac.jp/ctr/ as UMIN000000511, is a nation-wide multi-institutional study and recruited 447 eligible children (age <18 years) with de novo AML from 11/1/2006 to 12/31/2010 (acute promyelocytic leukemia and Down syndrome patients excluded). Three patients including 2 children with t(8;21) who discontinued from the study during induction therapy are excluded from the efficacy analyses: one protocol violation, 1 changing to non-JPLSG member hospital at the patient's request, and 1 withdrawal of the JPLSG institutional membership. After 2 courses of common induction therapies, patients were stratified by the specific cytogenetic characters and morphological treatment response into 3 risk groups. Patients with CBF-AML, t(8;21) or inv(16), and good bone marrow response to the first induction course were stratified to the low risk (LR) group, and further received 3 courses of chemotherapy; 4/5 courses consisted of HD Ara-C, and the total cumulative dose of anthracyclines, Mitoxantrone and Idarubicin, was reduced from 300 to 225 mg/m2 compared to the LR chemotherapy in the previous AML99 study (Tsukimoto I. J Clin Oncol 2009;27:4007–13). Conversion rate of 5:1 was used to compare the cumulative dose of Daunorubicin and Mitoxantrone/Idarubicin. Results: Three-year probability of event-free survival (pEFS) and 3y-pOS of all 444 patients was 55.3% (95%CI, 50.2 – 60.1%) and 73.2% (68.3 – 77.5%), respectively. The median follow-up period for living patients was 3.06 years (range, 0.84 – 5.36 years). One hundred fifty-five CBF-AML patients [34.9%; t(8;21), N=123 (27.7%); inv(16), N=32 (7.2%)] in the AML-05 and 89 patients [37.0%; t(8;21), N=77 (32.0%); inv(16), N=12 (5.0%)] in AML99 were compared. There were no differences in basic characteristics such as sex and age/WBC at diagnosis. CR rate was identical between the 2 cohorts (95.5% vs. 97.8%, p = 0.36). There was a tendency of lower 3y-pEFS in the AML-05 cohort [69.3% (95%CI, 60.8 – 76.3%) vs. 80.9% (71.1 – 87.7%), p = 0.078], however, 3y pOS did not differ [92.2% (85.8 – 95.8%) vs. 92.1% (84.2 – 96.2%), p= 0.94]. One hundred thirty-six CBF-AML patients were stratified to the LR group in AML-05; 8 patients were stratified to the HR group and allocated to allogeneic hematopoietic transplantation in 1CR because of poor treatment response (N=5) or FLT3-ITD positivity (N=3), and 11 patients were off protocol therapy before risk stratification because of various reasons. These 136 LR patients were compared with 83 CBF-AML patients in AML99 who fulfilled AML-05 LR criteria; 7/83 t(8;21) cases with WBC ≥ 50,000/μL in AML99 received intermediate risk (IR) chemotherapy with 375 mg/m2 of anthracyclines according to the protocol. The 3y-pEFS was significantly lower in the AML-05 cohort [69.6% (60.6 – 77.0%) vs. 83.1% (73.2 – 89.6%), p = 0.041], although the 3y-pOS was not different [92.6% (85.6 – 96.3%) vs. 94.0% (86.1 – 97.5%), p= 0.74]. Conclusions: The pEFS of children with CBF-AML treated with very low cumulative dose of anthracyclines were inferior to the historical control even treated with intensive use of HD Ara-C, therefore, caution is needed to reduce cumulative anthracycline doses to below 300mg/m2. However, the fact that nearly 70% of the CBF-AML patients are cured with lower dose of anthracyclines suggest the presence of underlying biological factors to be identified for future stratification of CBF-AML in children. Disclosures: No relevant conflicts of interest to declare.

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Secondary Acute Myeloid Leukemia Is an Heterogeneous Subgroup of Elderly AML Where Patient’s Fitness Criteria and ELN Prognostic Stratification Can be Applied to Guide Treatment Decisions: An Analysis of 127 Patients By the Network Rete Ematologica Lombarda (REL)

Blood ◽

10.1182/blood.v124.21.953.953 ◽

2014 ◽

Vol 124 (21) ◽

pp. 953-953

Author(s):

Erika Borlenghi ◽

Chiara Pagani ◽

Claudia Basilico ◽

Massimo Bernardi ◽

Matteo Carrabba ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Risk Stratification ◽

Myeloid Leukemia ◽

De Novo ◽

Treatment Modalities ◽

Secondary Acute Myeloid Leukemia ◽

Elderly Aml ◽

Prognostic Stratification ◽

De Novo Aml ◽

Acute Myeloid

Abstract Background: According to the WHO classification, secondary acute myeloid leukemia (s-AML) includes cases occurring in patients (pts) receiving prior antineoplastic treatments as well as cases developing in pts with a history of previous hematology disorders, such as a myelodysplastic syndrome (MDS) or a chronic myeloproliferative disease (MPD). Outcomes for this large group of pts, which has a high median age and a high frequency of unfavourable cytogenetics, has been traditionally considered very poor, compared to AML developing “de novo”, and treatment with intensive chemotherapy (iCT) is not standardized in elderly pts. Indeed pts with s-AML have been excluded from molecular and cytogenetic prognostic stratification defined by the ELN criteria. Aim: Since patients with s-AML actually represent an heterogeneous subgroup of pts a multicenter retrospective study was performed to analyse their outcome in relationship to age, fitness and ELN risk stratification, in order to potentially identify subgroups at different prognosis. Patients and Methods: We evaluated 127 pts, representing 35% of a population-based series of elderly AML, aged > 65 years (y), diagnosed at five Hematology Centers of the Hematological Network of Lombardy in Northern Italy from January 2008 to May 2014. Thirteen pts (10%) had t-AML and 114 (90%) had AML secondary to previous hematological disorders (89 MDS and 25 MPD). Median age was 74 y (range 65-94 y). Performance status (PS) was evaluable in 122 pts (96%) and PS ECOG was >3 in 32 pts (26%). According to “fitness criteria”, (Ferrara et al, Leukemia, 2013), 126 pts (99%) were evaluable: 54 pts (42.5%) were fit to i-CT (FIT), 55 (43.3%) unfit to i-CT (UNFIT), 17 (13.4%) unfit to ni-CT (FRAIL). Intensive CT was given to 34 (27%), ni-CT (low-dose arac, azacytidine or experimental non-myelotoxic drugs) to 26 (20%) and best supportive care (BSC) to 67 pts (53%). Overall concordance between the fitness and the treatment actually received was 78%.The ELN prognostic criteria were applicable in 69 pts (54%), because of lack of complete molecular and cytogenetic data in the others. Six pts (8.5%, all NPM1+) were at low, 14 (20%) at intermediate-1, 11 (16%) at intermediate-2 and 38 (55%) at high risk. Results: The median OS according to fitness was 9,6, 4 and 3 months (ms), in FIT, UNFIT and FRAIL pts, respectively (p=0.0021) (Figure 1). Both the treatment received (i-CT or ni-CT vs BSC) and the risk ELN classification were related to OS (p< 0.0001 and p=0.0089, respectively). In FIT pts the median OS was 8 ms in pts treated with i-CT, 11 ms with ni-CT, and 3 ms with BSC (p<0.0001) (i-CT vs ni-CT : p=0.6) (Figure2). The achievement of CR was related to outcome (median OS 12.7 ms vs 5 ms) (p= 0.0035). AML with antecedent hematological disorder (53.8%) or with t-AML (50%) had similar CR rate (53,8% vs 50%) as well as OS (median OS 11 ms vs 7 ms) (p =0.5). According to ELN risk, OS was better in LR/Int-1/int2 vs HR (median OS 11,4 vs 5 ms, p=0.0035) (Figure 2). Moreover, also the achievement of CR was related to ELN risk: 100% in LR, 57% in Int1/Int2, 14% in HR (p= 0.012), and percentages differed from de novo AML only in HR pts. Prognosis of the subgroup of 34 ELN low/Int1 risk pts treated with i-CT was fair with CR rate of 53%, and 2 y OS 40% compared to 10% in similarly treated Int2/HR pts (p=0.07). Conclusion: Elderly pts with s-AML are an heterogeneous subgroup both according to fitness and to ELN risk stratification and these parameters are significantly related to clinical outcome. Overall prognosis of elderly patients with s-AML is not exceedingly worse than in elderly with de novo AML. Outcome was better using i-CT or ni-CT compared to BSC, with no differences between the two treatment modalities. ELN risk stratification merits to be applied also to patients with s-AML and its integration with fitness criteria can identify a subgroup of patients which may benefit from intensive CT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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