ALBERT

Description: Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity. In this Intergroupe Francophone du Myélome (IFM) phase 2 study, 54 untreated patients were enrolled between July and December 2007 to receive bortezomib (1 mg/m2 × 4) and melphalan (200 mg/m2) as conditioning regimen (Bor-HDM). Overall, 70% of patients achieved at least VGPR, including 17 patients with CR (32%) after ASCT. No toxic deaths were observed. Bortezomib did not increase hematologic toxicity. Only 1 grade 3 to 4 peripheral neuropathy was reported. A matched control analysis was conducted comparing our cohort with patients from the IFM 2005-01 trial (HDM alone). Patients were matched for response to induction therapy and type of induction: CR was higher in the Bor-HDM group (35% vs 11%; P = .001), regardless of induction therapy. These results suggest that Bor-HDM is a safe and promising conditioning regimen. Randomized studies are needed to assess whether this conditioning regimen is superior to HDM alone. This trial was registered at www.clinicaltrials.gov as NCT00642395.

Description: The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK+ patients had a complete response rate significantly lower than MK− patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P 〈 .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK+ patients, survival was dramatically decreased for MK+ patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.

Description: The prognosis of poor risk AML in elderly pts justifies either supportive care only or investigational studies without obvious benefit of post-remission chemotherapies. A phase I study has demonstrated that the combination of azacitidine and lenalidomide is well-tolerated in AML with efficacy superior to that of single-agent therapy in higher-risk MDS (Sekeres JCO2010). The GOELAMS group investigated the efficacy of 12 maintenance cycles alternating monthly azacitidine (sc 75 mg/m²/d1-7) and lenalidomide (10mg/d1-21) every 28 days for pts in CR and compared the results to previous SA2002 and BGMT95 prospective trials which shared the same LIA induction followed by chemotherapy-based maintenance. Between 3/2011 and 2/2013, 117 pts from 27 centers (median age 69 yrs; 60-80, 9 pts ≥ 75) with previously untreated poor prognosis AML were included. Risk factors allowing inclusion were either: i) centrally reviewed (IL) poor risk cytogenetics (n=83) defined as complex karyotype (≥3 abnormalities), monosomal karyotype, t(6;9), del or – 5 or 7, and EVI1 or MLL rearrangement except for t(9;11); ii) preceding MDS (n=52) or iii) secondary leukemia occurring after previous cancer (n=37). Median WBC was 2.9 G/L (0.5-160), 19 pts had WBC 〉 30 G/L. Induction chemotherapy included lomustine 200 mg/m² po d1, Idarabucine 8 mg/m²/d (d1-5), cytarabine 100mg/m²/d CI (d1-7) and G-CSF (d15 to recovery). At the end of induction, CR (excluding CRp) was achieved in 56% (65 pts), 9% died from infection (n=6), cerebral hemorrhage (n=1) or multiorgan failure (n=4) and 35% (41pts) failed to achieve CR. Despite a trend towards a higher CR rate in pts without previous MDS (59% vs 48% CR), CR was not related to any of the risk factors studied. Median follow-up for survivors is 16 months (3-25). Monthly alternating azacitidine-lenalidomide maintenance therapy was started in 65 pts. Except for 1 pt who died during cycle1 of lenalidomide without any obvious explanation, tolerance was good. Median nadir of neutrophils and platelets was 1 and 96 G/L respectively. Grade 3/4 adverse events occurred in 6% of cycles and were due to infection, haemorrhage, hepatitis or fatigue (3%, 1%, 0.5%, 0.5% of cycles respectively). Median CR duration was 4.5 mo (1-23) and 40 pts relapsed. Allogeneic SCT with non myelo-ablative preparative regimen was performed in 4 pts less than 70 years in CR1: 1 is alive in relapse, 2 died of GVH and 1 is in continuous CR. Pts achieving CR had a median OS of 13 mo (95% CI 7.3-18.6), 54% being alive at 1 year and 15% at 2y. In refractory pts, the median OS was 7 mo (95% CI 2.8-11.2) with 32% alive at 1 year (P = 0.0001). OS and DFS reported in the current trial and compared to historical controls are described below: induction results are similar to those observed in the 128 poor risk cytogenetic pts of the previous SA2002/BGMT trials treated with the same LIA induction (CR 58%, early death 15%, failure 27%) but who received maintenance therapy with 6 mini-reinductions (Ida 10mg/m² d1, cytarabine 50 mg/m²x2/d d1-5) and 6MP-MTX for 2years. No significant survival benefit was observed compared to pts with poor risk cytogenetics treated with chemotherapy maintenance in our previous trials. However, pts included in this trial have probably an even worse prognostic than those included in the GOELAMSSA2/BGMT95 trial which excluded AML secondary to MDS and previous cancers. This type of alternating azacitidine/lenalidomide maintenance improves OS and DFS of pts without poor risk cytogenetics (median DFS not reached and 19 mo) and could be randomly compared with conventional chemotherapy maintenance in AML secondary to MDS or cancer but also in older pts with intermediate risk cytogenetics.Median (95% CI)6mo1y2yOS maintenance aza-rev (117)9 mo (7.5-10.5)70%41%17%OS 2002/BGMT95 (128)6 mo (4.1-7.8)54%32%21%DFS maintenance aza-Rev (65)10 mo (2.5-17.4)61%49%8%DFS 2002/BGMT95 (74)9 mo (6.0-11.9)63%43%26%OS poor risk cytogenetic (83) vs other (33)8 mo vs NR P=0.000162% vs 83%27% vs 70%10% vs 60%OS previous cancer (37) vs no cancer (80)9 mo vs 9 mo68% vs 73%44% vs 40%24% vs 17%OS previous MDS (52) vs no MDS(64)12 mo vs 7 mo P=0.00177% vs 65%58% vs 26%27% vs 12%DFS poor risk cytogenetic (44) vs other (20)6 mo vs 19 mo P=0.00748% vs 84%33% vs 67%11% vs 28%DFS previous cancer (20) vs no K(45)8 mo vs 8 mo80% vs 61%46% vs 47%0% vs 13%DFS previous MDS (27) vs no MDS(38)15 mo vs 6 mo, P=0.0874% vs 48%59% vs 32%12% vs 0% Disclosures: No relevant conflicts of interest to declare.

Description: Key Points GO before transplant improves outcome of CBF-AML patients in first relapse.

Description: Abstract 2608 Aim. CBF-AML is a favorable AML subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, respectively responsible for RUNX1-RUNX1T1 (CBFα) or CBFB-MYH11 (CBFβ) gene fusion. Nonetheless, relapse incidence may reach 30–40% in these patients. The tyrosine kinase (TK) receptor KIT is expressed in the vast majority of CBF-AML and activating KIT gene mutations, including exon 8 del/ins and exon 17 point mutations, have been reported in both CBF-AML subtypes. These mutations have been retrospectively associated with a higher risk of relapse. Dasatinib is a TK inhibitor active on both wild-type and mutant KIT isoforms. These observations led several groups to initiate prospective trials testing dasatinib/chemotherapy combinations in newly diagnosed CBF-AML patients. The aim of the present Phase 2 DASA-CBF trial (EudracCT 2006-00655-12) was to search for a positive signal by treating CBF-AML patients in first complete remission (CR), but with persistent or re-appearing molecular minimal residual disease (MRD), by the single-agent dasatinib. Prevention of further hematological relapse was the primary endpoint. Methods. Eligible patients (18–60y) had to have been previously enrolled and treated in the CBF-2006 study (Jourdan et al. this meeting). MRD was quantified by RQ-PCR and results were expressed as 100 × CBF fusion gene/cABL ratios. Patients in first CR were eligible if: 1) MRD ratio reduction less than 3-Log before the second consolidation cycle (refractory Mol-REF patients); or 2) MRD ratio re-increase more than 1-Log on two successive evaluations (relapsing Mol-REL patients). Patients with a sibling or unrelated donor and no contra-indication to allogeneic stem cell transplantation (SCT) were not eligible. Dasatinib was administered orally at 140 mg once daily for a total duration of 12 months. In case of grade 3 adverse event (AE), treatment was discontinuated until AE resolution to grade 0–1. In case of grade 4 AE or AE reappearance, dose reduction to 100 mg/d was allowed. Dose escalation to 90 mg bid was allowed in case of stable or increasing MRD after 2 months of therapy without toxicity. Results. Between June 2008 and June 2011, 26 CBF-AML patients (median age, 44y) were included. They were 12 CBFα patients (6 Mol-REF, 6 Mol-REL) and 14 CBFβ patients (12 Mol-REF, 2 Mol-REL). Seven patients had a KIT mutation (4 exon 8 and 3 exon 17; 3 CBFα and 4 CBFβ). The median time between CR achievement and DASA-CBF enrollment was 161 days (106–406) in Mol-REF patients and 413 days (167–530) in Mol-REL patients. Overall, dasatinib was well tolerated. Two grade 3 AEs (hypertension, headache) led to dasatinib dose reduction without further reoccurrence. Dose escalation was performed in two patients. With the exception of one patient (without KIT mutation) still alive in CR1 at 929 days, 7 of the 8 Mol-REL patients had rapid hematological relapse under dasatinib treatment after a median time of 60 days (52–120). In the 18 Mol-REF patients, the probability of persistent hematological remission was 65% (95% CI, 38–82) at 12 months and 45% (95% CI, 20–67) at 24 months, with a trend for shorter remission duration in the 6 patients with KIT mutation (P=0.07). These 18 Mol-REF patients were compared to the 37 other Mol-REF patients from the CBF-2006 trial not enrolled in the DASA-CBF trial (9 SCT in CR1, 28 without further therapy). Both series were comparable in terms of age, WBC, baseline fusion transcript ratio, MRD ratio Log-reduction after induction and first HDAC consolidation, as well as additional cytogenetic anomalies and KIT, FLT3 and RAS gene mutations. Despite dasatinib treatment, the probability of persistent hematological remission was not higher in the 18 DASA-CBF patients than in the 28 patients who received no further therapy (45% versus 53% at 24 months, P=0.91). Conversely, only one hematological relapse was observed in the 9 patients who received SCT in CR1, the remaining 8 patients being alive in continuous CR. Conclusion. This Phase 2 trial failed to show a significant effect of single-agent dasatinib in the prevention of hematological relapse in CBF-AML patients in first CR after standard therapy, but at high risk of relapse because of persistent or re-appearing MRD. Moreover, no trend towards a preferential effect was observed in KIT mutated patients. This observation does not preclude any dasatinib activity in CBF-AML patients when combined with conventional chemotherapy. Disclosures: Off Label Use: Dasatinib is not approved for AML patients. Mohamed:Bristol-Myers Squibb: Employment.

Description: Abstract 79 The prognosis of acute myeloblastic leukemia (AML) with intermediate-risk cytogenetics is refined further by testing the mutational status of NPM1,FLT3 and CEBPa genes. Patients with a NPM1mutFLT3wt and CEBPa double mutation are now classified in a separate favorable group of the new ELN classification. Conversely, all other molecular profiles including these 3 genes, considered as carrying a worse prognosis, are included in ELN intermediate groups 1 and 2. Nevetheless the therapy of AML has remained unchanged since many years and needs improvement even in this subset of patients. The GOELAMS has tested the association of gemtuzumab ozozgamycin (GO), a monoclonal anti-CD33 antibody conjugated with chalicheamycin to standard chemotherapy in a phase III prospective randomized trial focusing on such patients with intermediate cytogenetics. Methods: Between 2007 and 2010, 254 patients aged between 18 to 60 years with de novo AML and intermediate karyotype have been included. The molecular status for NPM1, FLT3 and CEBPa mutations was determined at diagnosis. After 1/1 randomization, GO 6m/m2 was added to standard 3+7 induction and to a first MidAc intensive consolidation course (Mitoxantrone and intermediate doses of cytarabine). Patients in the ELN favorable molecular group received a second MidAc course followed by an autologous bone marrow transplant (BMT). Patients in the ELN intermediate 1 or 2 groups were considered for geno or phenoidentical allogeneic transplant. Patients 50 years of age or lower, received either standard allo-BMT preceded by a single course of chemotherapy or a reduced intensity chemotherapy (RIC) regimen after the two courses of intensive consolidation. In this sub-group, patients with no donor received autologous BMT after the two randomized courses of consolidation. Results: Two hundred and thirty-eight patients were analyzed with a median follow-up of 20 months. Their median age was 50 years old (18–60). There was no significant difference between the two arms according to age, WBC, % of circulating and % of marrow blasts, FAB subtypes, cytogenetics (normal vs abnormal) and molecular subgroups (favorable versus intermediate 1 and 2 ELN groups). In the GO group, the complete remission (CR) rate was 91.6% versus 86.5% (P=NS), early death(ED) was 10% versus 4.5% (P=NS). Major toxicity was observed in the GO arm during induction phase with 4 cases of veno-occlusive liver disease (VOD) and overall more toxic grade III/IV hepatic toxicities (23% versus 13%, p=0.031). No significant difference was observed between the two arms for grade III/IV hematological toxicity. No difference was observed either at 3 years for event free survival (EFS) at 51% in the GO arm and 33% in the other arm, nor for overall survival (OS) at respectively 53% and 46%. In the subset of patients who could not receive an allogeneic transplant, EFS was significantly higher in the GO group (53.7% vs 27%, p=0.0308) while there was no difference for OS. This better outcome was mostly observed in the group of patients classified ELN intermediate 1 or 2 (p=0.0126). Conclusion: In the subset of patients with intermediate cytogenetics AML, the adjunction of GO to standard chemotherapy failed to improved OS, yet a better EFS was observed with the addition of GO for patients who could not receive an allogeneic SCT. More detailed results will be presented. Disclosures: No relevant conflicts of interest to declare.

Description: The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P = .74). However, the CR plus very good partial response (VGPR) rate was significantly higher in the vtD arm (49% vs 36%, P = .05). After ASCT, the CR plus VGPR rate was significantly higher in the vtD arm (74% vs 58%, P = .02). The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy (PN): grade ≥ 2 PN were reported in 34% in the VD arm versus 14% in the vtD arm (P = .001). vtD, including reduced doses of bortezomib and thalidomide, yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT. This study was registered with www.clinicaltrials.gov as #NCT00910897 and EudraCT as #2007-005204-40.

Description: Abstract 2603 Purpose Although CBF-AML (i.e. with t(8;21) or inv(16)/t(16;16)) represents a favorable cytogenetic AML subgroup (Döhner, Blood 2010), 35–45% of these patients still relapse after standard intensive chemotherapy. The immunoconjugate gemtuzumab ozogamicin (GO) was shown to be effective in patients with relapsed AML in non randomized studies and has been recently demonstrated in a Phase 3 trial as associated with a significant benefit in younger adults with CBF-AML (Burnett, JCO 2011). In this study, we thus investigated the impact of GO-based salvage at first relapse in this specific subgroup of patients with CBF-AML. Patients and Methods We retrospectively analysed the medical records of 84 patients aged 60 years or less with CBF-AML in first relapse after intensive chemotherapy and treated in 18 French centers. None of these patients received allogeneic (alloSCT) or autologous (autoSCT) hematopoietic stem cell transplantation in first complete remission (CR). As salvage, 27 patients received GO, combined with high-dose cytarabine in most of them; 21 patients received high-dose cytarabine and anthracycline without GO; 36 patients received conventional chemotherapy based on standard-dose cytarabine and anthracycline. Post-remission therapy was alloSCT in 49 patients, autoSCT in 17 patients, and chemotherapy alone in 11 patients. Results Among 84 patients with a median age of 39 years [16–58], 36 patients had t(8;21) AML and 48 patients had inv(16)/t(16;16) AML. Median CR1 duration was 12.9 months [2.6–55.3]. Second complete remission (CR2) rate was 92% (77/84), and early death rate was 1% (1/84). The median follow up was 4.0 years. The 5-year overall survival (5y-OS) and relapse-free survival (5y-RFS) was 52% [39–64%] and 48% [36–60%] respectively. Patients receiving alloSCT in CR2 had a better outcome (5y-OS, 56% versus 43%; p=0.05). In patients not allografted in CR2, RFS was similar after autoSCT and chemotherapy alone (5y-RFS, 44% versus 47%, respectively). Patients treated with GO had similar CR rate but a lower risk of second relapse and a better survival than other patients (5y-RFS, 89% versus 55%; p=0.05 and 5y-OS, 90% versus 45%; p=0.03). In univariate analysis, other factors associated with a better OS were younger age, longer CR1 duration, but not CBF subtype (p=0.03, 0.01, and 0.20, respectively). In multivariate analysis adjusted on age, CR1 duration, and CBF subtype, GO salvage was still associated with a significant benefit in OS (HR=0.16 [0.04–0.69], p=0.01) and RFS (HR=0.19 [0.04–0.80], p=0.02). With a median post-relapse follow-up of 2.2 years, no relapse nor death were observed in the 19 patients who received GO salvage followed by alloSCT in CR2 (p=0.007 for RFS; p=0.008 for OS). Moreover, in patients who received alloSCT, previous GO therapy significantly improved post-transplantation outcome. Conclusion Younger patients with CBF-AML in first relapse had a high second complete remission rate regardless the intensive chemotherapy salvage. More interestingly, the outcome of these patients was significantly improved by the addition of GO-based salvage, especially when followed by alloSCT. Disclosures: Off Label Use: GO is available in Europe as a compassionate treatment for relapsed AML.

Description: From 11/01 until 04/05, 832 patients under 60 (median age = 46, 18–60) were included in AML1 protocol for treatment of de novo AML (AML3 and previous diagnosis of MDS or MPS were excluded, unlike previous diagnosis of solid tumor and/or chemo-radiotherapy without subsequent MDS). Among these 8 patients presented with exclusion criteria (acute phase of CML = 5, AML3 = 1; age 〉 61 = 2). All patients received induction therapy according to: 1 st randomisation: classical 3 + 7 (Dauno 60 mg/m2/d, ARAC 200 mg/m2/d CI) vs 5 + 7(Ida 8 mg/m2/d); residual blasts in bone marrow at D15: if 〉 5%: second course with same anthracyclin 2 d + intermediate dose ARAC 1 g/m2 × 2/d for 4 days. 82% were considered in complete remission (CR) after 1 or 2 (26%) induction courses. At remission patients were allowed to following arms according to: presence of an HLA identical sibling: arm M) if age 〈 50: prompt bone marrow allograft with myeloablative conditioning regimen; arm m) if age 〉 50: peripheral blood stem cells (PBSC) allograft after reduced intensity conditioning regimen and previous intensive consolidation (IC) with HD ARAC; arm C) no allograft (and 2 IC with HD ARAC) if good prognosis (CBF AML and CR after 1 course) absence of such a donor and subsequent 2nd randomization: arm A) IC followed by single autologous PBSC autograft (Busulfan 16 mg/kg and HD Melphalan 140 mg/m2); arm B) IC followed by to 2 PBSC autografts ( HD Mel 200 mg/m2 then BuMel as previous arm) Preliminary results were presented at the 2006 ASH meeting (Abstr 319 and 608). In the present study, we tried to establish prognostic value for DFS and OS of absolute lymphocyte count (ALC) at 1st CR: 629 patients were assessable for this analysis. Median follow up is 35 months. Median ALC was 1,17 +/− 0,74 (range 0,08–7,9). In univariate analysis, patients with ALC at 1st CR above the median value have significant better DFS but no significant different OS (Logrank test). For patients not receiving allografts, this advantage remains significant for both DFS and OS. Best OS advantage was observed for good prognosis patients (CBF AML) as it was not significant for DFS and other prognostic groups according to cytogenetics. ALC above median ALC under median p All patients (n = 629) Median DFS undefined 30 months 0,038 0,08 Median OS undefined 63 months Patients not receving an allograft ( n = 428) Median DFS undefined 21 months 0,041 0,039 Median OS undefined 59 months Patients with CBF AML not receving an allograft ( n = 87) Median DFS undefined undefined 0,159 Median OS undefined undefined 0,029 Difference occurs as soon as soon as 12 months after diagnosis as shown in survival curves below (i.e. short term relapses). Figure Figure Conclusions: these results confirm in a large prospective trial previous data establishing good prognostic value of higher ALC value at 1st CR of AML; this effect is mostly seen among patients not proceeding to allograft as consolidation for 1st CR and for patients with CBF AML; this may represent an immunological platform for other additional therapies with immunostimulant properties (as may be lenalinomide for example) applied during or soon after consolidation courses.

Description: Abstract 410 Background. CBF-AML is a favorable AML subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, respectively responsible for RUNX1-RUNX1T1 (CBFa) or CBFB-MYH11 (CBFb) gene fusion. Nonetheless, relapse incidence may reach 30–40% in these patients. Even if not yet prospectively validated, early MRD monitoring based on chimeric fusion gene transcript quantification by RQ-PCR may help to define patients at higher risk of relapse. Detection of activating KIT and FLT3 gene mutations has also been retrospectively associated with higher relapse rate in these patients. The French CBF-2006 trial (NCT00428558) aimed to prospectively evaluate both markers as predictors of remission duration in homogeneously treated patients. Methods. Patients (18–60y) with newly diagnosed CBF-AML were eligible. All were studied for KIT exon 8/17, FLT3-ITD, FLT3-D835, N-RAS and K-RAS mutations. They were randomized to receive timed-sequential or standard induction. Timed-sequential induction was cytarabine (AraC) 500 mg/m2 CI D1-3 and daunorubicine (DNR) 60 mg/m2 D1-3, followed by AraC 1 g/m2/12h D8-10 and DNR 35 mg/m2 D8-9. Standard arm was AraC 200 mg/m2 CI D1-7 and DNR 60 mg/m2 D1-3, followed by the second sequence at D16-18 only in case of persistent bone marrow (BM) blasts at D15. Patients in first complete remission (CR1) received 3 HDAC consolidation cycles with AraC 3 g/m2/12h D1/3/5. Fusion gene expression was quantified at baseline and before each HDAC cycle (MRD1, MRD2, MRD3) by the 100 × fusion gene/cABL ratio. Patients not reaching a 3-Log ratio reduction at MRD2 were offered allogeneic stem cell transplantation (SCT) in CR1 if they had an HLA-identical donor or could enter a single-agent dasatinib sub-study (see Boissel et al., this meeting). Results. Among the planned 200 patients randomized, 198 met eligibility criteria (96 CBFa and 102 CBFb, compared in Table 1). Overall, incidences of KIT, RAS, FLT3-D835 and FLT3-ITD mutations were 21%, 29%, 10% and 6%, respectively. Patients with KIT and FLT3-D835 mutations had higher WBC (P=0.04 and 0.02) and BM blast percentage (P=0.0004 and 0.05). Those with RAS mutations had lower BM blast percentage (P=0.01) and baseline transcript ratio (P=0.001). Overall, 196 patients reached CR1 and 55 relapsed. At 3 years, probabilities of durable remission, disease-free (DFS) and overall survival from CR were 64%, 61% and 84%, respectively, without differences between the CBF subsets or induction arms. Fifty-five patients did not reach the 3-Log MRD2 reduction (18 CBFa and 37 CBFb, P=0.006), 9 receiving SCT in CR1. Poor MRD2 response correlated with age (P=0.01), WBC (P=0.04), KIT mutations (P=0.04), and initial transcript ratio (P=0.004). Among the characteristics listed in Table 1, shorter remission duration was associated with high WBC (P=0.011), high BM blast percentage (P=0.062), del(9q) (P=0.041), KIT mutation (P=0.048), FLT3-D835 mutation (P=0.077), high initial transcript ratio (P=0.053), and