Post Remission Research Articles

Presence of Minimal Residual Disease at End of Induction in Acute Myeloid Leukemia Is Predictive of Poor Outcome

Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML), other than acute promyelocytic leukemia, is induction with a goal to achieve morphological complete remission (CR) as evident by less than 5% blasts. Post remission strategies then focus on either consolidation chemotherapy or allogeneic bone marrow transplantation (aBMT). However, not all patients by this remission criterion achieve long term remission and a subset of patients relapse. This relapse originates from further expansion chemoresistant clones. Detection of minimal residual disease (MRD) following chemotherapy, early in the course of treatment, is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse. Here, we describe assessment of immunophenotypic MRD using a 10-colour two tube assay and a “difference from normal” approach.Methods: We accrued 280 consecutive patients of adult (>18 years) AML, other than with t(15;17), over a 30 month period after obtaining consent. All patients received “3+7” induction therapy with daunorubicin and cytarabine. If patients were in morphological CR at end of induction, they either received 3 courses of 12-18 gm/m2 high dose cytarabine (HiDAC) or aBMT if feasible.MRD testing was done at end of induction and if feasible, post 1st Cycle HiDac using a two tube 10 colour assay. (CD15, CD13, CD19, CD34, CD56, CD7, CD45, CD11b, HLA-DR, CD117, CD14, CD123, CD64, CD33, CD36 & CD38). A minimum of 1.6 million events were acquired per tube on a Navios flow cytometer. Identical panel was used at MRD time points as well as on the diagnostic sample. Analysis of MRD was done using Kaluza 1.3 by a difference from normal approach that focused on the development of progenitors to monocytes. Conventional karyotyping and FISH was done as per standard recommendations and patients were classified into favorable, intermediate and poor cytogenetic risk. The presence of FLT3 -ITD, NPM1 and CEBPA mutations was detected by a fragment length analysis based assay. Overall survival (OS) was calculated from date of diagnosis to time of last follow up or death. Relapse free survival (RFS) was calculated after achieving of 1st remission (CR) till relapse or death or last follow up if in CR. Results of the MRD assays, cytogenetic and molecular risk groups were analyzed for their impact on OS and DFS using Log Rank test of Kaplan-Meier survival analysis.Results: A total of 280 AML patients were treated and followed up till maximum of 30 months period. Based on cytogenetics, 28.6% were classified as favorable risk whereas 61.4% and 10% were intermediate and poor risk respectively. FLT3-ITD, NPM1 and CEBPA mutations were harbored by 20.7%, 26.4% and 10.3% of patients respectively. The median follow up was of 9 months (Ranging from 17 days to 30 months). Of these, 35 had induction death and 59 had refractory disease. Median OS was 50.3% and RFS was 50.9%. Post induction MRD was assessed in 235 patients of which 108 (45.9%) had detectable residual disease (range 0.01-66%, median:1.38%). Post consolidation MRD was assessed in 98 patients of which 22 (22.4%) were MRD positive (range 0.002-7.7%, median: 0.05%). Favorable risk cytogenetics in cases excluding induction deaths was predictive of better OS than intermediate (p= 0.031) and poor risk (p=0.003) cytogenetic profiles but not RFS. Patients harboring MRD at the end of induction were associated with worse OS (p=0.04) but not RFS, whereas post consolidation positive MRD status did not show significant change in OS and RFS.Conclusion: Our data is in agreement with other studies that determination of immunophenotypic MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post remission strategies in AML and should be incorporated into routine treatment algorithms. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Long Term Results of Patients with Acute Promyelocytic Leukemia of Recent Diagnosis Treated with Daunorubicin or Epirubicin in Induction Therapy

INTRODUCTION Acute Promyelocytic Leukemia (APL), is an hematological emergency due to a high early mortality rate because of hemorrhages. When diagnosed, specific and simultaneous actions are required, including the start of tretinoin and the necessary steps to treat coagulopathy.OBJECTIVE To learn the event free survival and the overall survival of patients with APL that are treated in a Mexican Medical Center with two different anthracyclines.MATERIAL AND METHODS Prospective, longitudinal, open comparative study. All patients diagnosed with APL by morphology were included, with t(15;17) and /or PML/RARα positive candidates to be treated with chemotherapy protocol denominated LAP-3, which consists on Induction: ATRA + Daunorubicin (availability from 2009-2012) or Epirubicin (2013-2015), 2 post remission therapies with anthracyclines, and two year continuance of Mercaptopurine, Metotrexate and ATRA during cycles of 25 days every 3 months. Patients with serious organic shortcomings, HIV positives and pregnant women were excluded.RESULTS 30 patients were analyzed: 17 men and 13 women. The average age was 36 (16-73), the median line leukocytes was 4.5/mcl (400-370,000) of platelets 42,000 (9,000-386,000), the hematocrit 25% (6 to 42), fibrinogen of 233mg (22 to 730). 11 patients had high risk, 8 intermediate risk, and 11 low risk. 15 of them were treated with Induction with Daunorubicin and 15 with Epirubicin, only 4 patients developed ATRA syndrome; there were 7 deaths during the first 30 days, 5 from DIC (disseminated intravascular coagulation) and 2 from infection. 23 patients were evaluated for remission and all of them received it (100%). The event free survival was 87% for Daunorubicin and 60% for Epirubicin (p=0.08) with a follow up of 72 months, and the Overall Survival 87% for Daunorbicin and 67% for Epirubicin (p=0.02). In the case of patients who were not treated with ATRA, the mortality was 100% (p=0.004).CONCLUSION Results prove that patients who were treated with Daunorubicin had a better prognosis than the ones treated with Epirubicin, and the main cause of death during the first month were the complications associated to DIC. DisclosuresNo relevant conflicts of interest to declare.

Novel insights of acute myeloid leukemia with CEBPA deregulation: Heterogeneity dissection and re-stratification.

Acute myeloid leukemia with bi-allelic CEBPA mutation was categorized as an independent disease entity with favorable prognosis, however, recent researches have revealed huge heterogeneity within this disease group, and for some patients, relapse remained a major cause of treatment failure. Further risk stratification is essentially needed. Here by reviewing the latest literature, we summarized the characteristics of CEBPA mutation profiles and clinical features, with a special intention of dissecting the heterogeneity within the seemingly homogeneous AML with bi-allelic CEBPA mutations. Specifically, non-classical CEBPA mutation, miscellaneous companion genetic aberrations and the presence of germline CEBPA mutation are three major sources of heterogeneity. Identifying these factors can help us predict patients at a higher risk of relapse, for whom aggressive treatment may be recommended. Novel therapeutic approaches regarding manipulating potentially druggable targets as well as the debate over post remission consolidation regimens has also been discussed.

AN ADVANCED REVIEW ON DIAGNOSIS AND TREATMENT AND EXTRA-INTESTINAL MANIFESTATIONS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel Diseases are mainly a group of bowel disorders which are generally associated with chronic inflammation of the intestinal tract due to the reason of an imbalance in the presence of the intestinal microbiota. Inflammatory bowel disease can have two different types based on their clinical pathology which are mainly Crohn’s Disease and Ulcerative Colitis. Both of these clinical sub-types are most likely to be focussed among all of the inflammatory bowel diseases due to their increasing risk of incidence as well as associated difficulties in their treatment. However, the main cause of inflammatory bowel disease has not been cleared till the date but from last three decades, there is a hub of researchnes being going on to get a clear idea about the cause of disease. Among these studies most of researchers have found the role of Nucleotide Oligomerization Domain 2 genes in the pathophysiology of disease. For the treatment of ulcerative colitis, there are severalapproaches available, based on the severity of the disease. Aminosalicylates are used to treat mild disease, use of corticosteroids is the effective treatment in the moderate case whereas use of cyclosporine in severe disease. In Crohn’s disease, drug choices are dependent on both location and behavior ofthe disease. Nowadays, the advanced treatments have been included such as use of monoclonal antibodiesor fusion proteins including anti-TNF drugs as biological therapy of disease. Also the post treatment remission of this disease makes it more complicated to be cured.

Response Adapted Therapy in ETV6/RUNX1-Positive Childhood Acute Lymphoblastic Leukemia Treated per Modified St Jude Total XV Study

Introduction: ETV6-RUNX1 is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a precursor-B phenotype. The presence of ETV6-RUNX1 has been associated with a relatively low rate of relapse in multiple studies. Relapses tend to occur late and have a better salvage rate than other ALL subtypes. Moreover, conflicting data in literature regarding the prognostic significance of ETV6-RUNX1 after accounting for age, initial count and treatment intensity. We sought to study the clinical features, therapy response in newly diagnosed ETV6-RUNX1-positive treated at King Hussein Cancer Center. Methods: Patients were treated per modified St Jude Total (XV) study, risk stratification was further refined by including minimal residual disease (MRD)measurements on day 15 and day 46 of remission induction therapy. Patients with the ETV6- RUNX1 fusion or hyperdiploidy without CNS or testicular disease and a satisfactory early MRD decline (<1% on day 15 and <0.01% on day 46) were classified as being low-risk for relapse and were treated on lower -risk arm regardless of age and leukocyte count. Results: Seventy patients (n=70) with ETV6-RUNX1-positive treated at our institution between May 2006 to October 2017. The median age at diagnosis, 5.8 years (range, 1.5-10.8). ETV6-RUNX1 was associated with favorable age between 1- and 6-years in 55 patients (79%), male gender in 41 patients (59%), initial leukocyte count <10 in 39 patients (56%), CNS status 1 in 100% of patients. The majority, n= 58 (83%) of patients had NCI standard risk (SR) and n=12 (17%) had NCI high risk (HR). Sixty-six patients (94%) had MRD <1% at day 15 and all patients achieved remission with MRD<0.01% at day 46 of remission induction. All patients were treated as LR ALL per modified St Jude total XV protocol. At median follow up of (36 months; range, 26 to 154), in the subgroups of ETV6-RUNX1-positive patients classified as NCI standard risk (SR)and NCI high risk (HR) the 5-year EFS estimates were 94.1% ± 3.2 and 82%±1(P=.13), 5-year OS estimates were 100% and 92% ± 8 (p=0.31) respectively. Conclusion: MRD treatment schema in ETV6/RUNX1 -positive patients have excellent outcomes if they achieved favorable response at day 15 and end of remission induction regardless of the age and Initial leukocyte count. Treatment reduction is feasible and declared safe for children with NCI-HR who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD post remission induction therapy. Disclosures No relevant conflicts of interest to declare.

The role of minimal residual disease in completing post induction phase remission status in acute lymphoblastic leukemia B cell

The role of minimal residual disease in completing post induction phase remission status in acute lymphoblastic leukemia B cell

Improved Post remission survival of non- favorable risk Acute Myelogenous Leukemia (AML) patients following initial remission induction therapy with FLAG+/-Idarubicin versus 3 + 7 (Anthracycline + Cytarabine)

The fludarabine, high dose cytarabine and G-CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The impact of choice of induction regimen on post remission survival remains unclear. We retrospectively analyzed 304 consecutive AML patients, with non-favorable NCCN risk who received initial treatment at our center with either 7 + 3 (n = 86) or FLAG+/-Ida (n = 218). Patients in the FLAG+/-Ida group were more likely to achieve remission after one course of induction (74 % vs 62 %, p < 0.001) and had a faster time to achieve CR (30 days vs 37.5, p < 0.001) compared to 7 + 3. The time from diagnosis to transplant was shorter among CR patients after FLAG+/-Ida compared to 7 + 3 (115 vs. 151 days, p < 0.003). The 3-year post-remission OS and DFS was significantly better for patients receiving FLAG-Ida at 54 % and 49 % compared to 39 % and 32 % for 7 + 3 respectively (P = 0.01). Factors associated with post-remission survival included age at CR1, NCCN risk, induction regimen (FLAG+/-Ida vs 3 + 7 h 0.62, p = 0.01) and receipt of HCT. Our data, with the limitations inherent to a retrospective analysis, shows that achieving CR after FLAG+/-Ida has better post remission survival than 7 + 3.

Dactinomycin in Acute Myeloid Leukemia with NPM1 Mutations

NPM1 mutations are frequent in acute myeloid leukemia (AML) and define a distinct entity according to the 2016 WHO classification. NPM1 mutations are generally associated with chemosensitivity and a favorable prognosis. However, outcome may vary according to co-mutational events, and still approximately 40% of patients relapse after achieving complete response. Wild-type NPM1 is mainly located in the nucleolus where it plays a key role in the regulation of ribosome biogenesis, protein synthesis and tumor suppression through TP53 activation. Mutated NPM1 loses its predominant nucleolar location and accumulates in cytoplasm contributing to leukemogenesis (Falini B, Blood 2011). Moreover, this mutational event leads to haploinsufficiency and cytoplasmic retention of wild type NPM1 creating a vulnerability to nucleolar stress. Indeed, complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug (Falini B, NEJM 2015). Here, we report our experience of off-label dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML. Inclusion criteria for this retrospective study were: age ≥ 18 years-old, AML with NPM1 mutation, relapsed or refractory disease as well as treatment-naive patients unfit for intensive chemotherapy. Patients should also have completed one cycle of dactinomycin 12.5 µg/kg/day for 5 days every 28 days. From September 2015 to February 2019, 26 patients received dactinomycin. Median age was 62.5y, WBC count was &gt; 50 giga/L in 8 patients (31%), 13 patients (50%) had FLT3-ITD mutation whereas 10 (38%) and 11 (42%) patients were classified as favorable or intermediate-I according to the ELN-2010 classification. There were 7 (27%) relapses post-allogeneic transplantation. Median number of dactinomycin cycle was 1 (1-8) and 7 patients (27%) received more than 3 cycles. Sorafenib was added in 6 patients with associated FLT3-ITD mutations whereas 2 others patients received ATRA in combination with dactinomycin. Dactinomycin was administered in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n=16, 62%) or molecular relapses (n=4, 16%) following intensive chemotherapy, refractory disease (n=1, 13%) or post remission therapy in second complete response (CR) following salvage chemotherapy (n=1, 13%). Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy reached complete remission after the first cycle of dactinomycin. The duration of response was 4 and 6 months in 2 patients whereas the third patient is still in CR 3 years after dactinomycin. One out of 4 patients in molecular relapses achieved a complete molecular remission with dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. The only patient treated in post-CR2 with dactinomycin achieved a complete molecular remission before allogeneic transplantation. Overall, 5 patients (19%) appeared to benefit from dactinomycin treatment. Grade 3-4 adverse events were thrombocytopenia (n=11, 42%), neutropenia (n=11, 42%), GI toxicity (n=6, 23%), mucositis (n=5, 19%), lung infection (n=5, 19%) and skin rash (n=2, 7.6%). Dactinomycin is an inexpensive and easily available drug that may induce significant responses in AML patients with NPM1 mutations with an acceptable safety profile. Prospective and controlled clinical trials are mandatory to clearly define the role of this agent in AML with NPM1 mutations. Disclosures Tavitian: Novartis: Membership on an entity's Board of Directors or advisory committees. Bertoli:Sanofi: Honoraria. Huguet:Incyte Biosciences: Honoraria; Servier: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria. Bories:Abbvie: Consultancy. Recher:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: NPM1 mutations are frequent in acute myeloid leukemia (AML) and define a distinct entity according to the 2016 WHO classification. Wild-type NPM1 is mainly located in the nucleolus where it plays a key role in the regulation of ribosome biogenesis, protein synthesis and tumor suppression through TP53 activation. Mutated NPM1 loses its predominant nucleolar location and accumulates in cytoplasm contributing to leukemogenesis (Falini B, Blood 2011). Moreover, this mutational event leads to haploinsufficiency and cytoplasmic retention of wild type NPM1 creating a vulnerability to nucleolar stress. Indeed, complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug (Falini B, NEJM 2015).

Fludarabine, Cytarabine, G-CSF and Gemtuzumab Ozogamicin (FLAG-GO) Regimen Results in Better Molecular Response and Relapse-Free Survival in Core Binding Factor Acute Myeloid Leukemia Than FLAG and Idarubicin (FLAG-Ida)

Fludarabine, Cytarabine, G-CSF and Gemtuzumab Ozogamicin (FLAG-GO) Regimen Results in Better Molecular Response and Relapse-Free Survival in Core Binding Factor Acute Myeloid Leukemia Than FLAG and Idarubicin (FLAG-Ida)

High Risk of Relapse with Intermediate Dose Cytarabine for Consolidation in Young Favorable Risk AML Patients Following Induction with 7+3

Introduction CALGB study in 1994 reported improved leukemia free survival (LFS) with sequential courses of high dose cytarabine (HIDAC- 3 gm/m2, q12h on days 1, 3 and 5) compared to lower doses of 100 mg/m2 and 400 mg/m2 per day. Following this study, HIDAC has been commonly used for chemotherapy consolidation in AML patients 60 years or younger. More recently, several groups investigated the role of intermediate dose cytarabine (IDAC-1.5 gm/m2 q12h D 1, 3 and 5 or D 1-3) in this population and reported equivalent outcomes for IDAC compared to HIDAC (Table 1). ELN guidelines published in January 2017 recommend IDAC for consolidation therapy in young (&amp;lt;60 years) favorable risk AML patients. Following these studies and ELN publication, consolidation protocols for AML patients 60 years or younger were changed from HIDAC to IDAC at Singapore General Hospital (SGH) in 2011 and at University of Minnesota Medical Center (UMMC) in February 2017. NCCN continues to recommend HIDAC as category 1 recommendation for consolidation of patients in this setting. We performed a combined analysis of outcomes in young favorable risk AML patients to assess impact of this change in practice on outcomes at our institutions as a quality initiative. Methods Patients 60 years or younger with ELN favorable risk AML between 2004 and 2015 at SGH and between September 2015 and March 2018 at UMMC, who underwent induction therapy with 7+3 regimen (idarubicin 12 mg/m2 D1-3 or daunorubicin 60 - 90 mg/m2 and cytarabine 100 mg/m2 continuous infusion from D1-7) and consolidation with cytarabine monotherapy were identified. These dates were chosen to allow reasonably equal time distribution before and after change in our practice. We extracted relevant outcomes data using chart review. We used Chi-square testing and applied Kaplan-Meier survival analysis to detect differences in relapse and survival outcomes. Results Of 67 ELN favorable risk patients 60 years or younger, 42 received HIDAC and 25 received IDAC. Median age was 39 years (range 16-59). 64 patients received 1 induction cycle and 3 patients received 2 induction cycles to achieve complete remission. Median LFS and overall survival (OS) with HIDAC vs IDAC were not-reached (NR, median time for follow up = 6.9 years) vs 1.35 years (p=0.004) and NR vs 2.27 years (p=0.001) respectively (Figure 1). Cumulative incidence of relapse at 2 years was 23.8% for HIDAC and 60% for IDAC groups (p=0.003). 3-year LFS and OS for HIDAC vs IDAC groups were 71% vs 36% (p=0.06) and 90% vs 48% (p=0.002). Discussion Historical data suggests chemotherapy consolidation with 3-4 cycles of HIDAC achieves long-term LFS of 60 - 70 % in young favorable risk AML patients. While the outcomes in HIDAC group in this study are comparable to historical data with good outcomes, a significantly larger proportion of patients in the IDAC group had early relapse (60%) and death. A major difference between the patients in this study and the other studies which showed similar outcomes with HIDAC and IDAC is the mode of induction. Data from large randomized studies in AML (Table 1) that suggest similar efficacy of IDAC compared to HIDAC used higher intensity induction regimens (frequently double induction therapy) compared to 7+3 and/or used other agents in combination with Ara-C for consolidation. These data are not broadly applicable in patients who receive a single cycle of 7+3 for induction, when selecting dose of Ara-C as monotherapy for consolidation. Furthermore, studies that used 7+3 for induction therapy showed benefit for HIDAC compared with multi-agent chemotherapy that included IDAC (Table 1). Conclusion Using single agent IDAC for post remission therapy is associated with higher rates of relapse and poor overall survival compared to HIDAC among young, ELN favorable risk AML patients who achieve complete remission following 7+3. The large randomized studies that suggested equivalency of IDAC to HIDAC for post remission therapy in AML patients, either used more than one cycle of intensive induction regimen and/or used cytarabine in combination with an anthracycline for consolidation. Hence, ELN guidelines should be cautiously interpreted given the above limitations in generalizability. Our study suggests that HIDAC, rather than IDAC, is the preferred chemotherapy consolidation regimen in young, favorable risk AML patients following standard 7+3 induction. Foot note: BK &amp; NAAH contributed equally. FH &amp; ZL contributed equally. Disclosures Kolla: Amgen: Equity Ownership. Weisdorf:Pharmacyclics: Consultancy; Incyte: Research Funding; Fate Therapeutics: Consultancy.

1. A relapsing case of Mi-2 antibody associated dermatomyositis with severe proximal weakness and bulbar involvement

1. A relapsing case of Mi-2 antibody associated dermatomyositis with severe proximal weakness and bulbar involvement

PS1011 MEASURABLE RESIDUAL DISEASE BY MULTIPARAMETRIC FLOW‐CYTOMETRY IS A RELIABLE TOOL FOR RISK‐STRATIFICATION OF FLT3‐MUTATED AML PATIENTS

Background:Mutations of the gene encoding Fms Related Tyrosine Kinase 3 (FLT3), both at the tyrosine kinase domain (TKD) and the juxta‐membrane level (ITD), represent the most common lesions found in Acute Myeloid Leukemia (AML),identifying a subgroup of patients with mainly unfavorable prognosis.FLT3 mutations are considered an unreliable tool for measurable (previously minimal) residual disease (MRD) monitoring, due to their intraclonal heterogeneity and instability during the course of disease. Instead, multiparametric flow cytometry (MFC) may represent a reliable tool to monitor MRD in this molecular subset. In fact,through the recognition and monitoring of leukemia associated immunophenotypes,MFC is applicable in up to 90% of AML patients with a sensitivity up to 10–4.Aims:The aim of our study was to investigate the feasibility of MRD assessment by MFC in FLT3 mutated AML. Furthermore, we investigated if MRD persistence in FLT3 mutated AML affects prognosis in terms of overall (OS) and disease‐free survival (DFS), as compared with FLT3 wildtype ones.Methods:We retrospectively analyzed a series of 39 patients with de novo AML carrying FLT3 mutations (34/39,87% ITD, 2/39, 5% TKD, 3/39, 8% ITD/TKD). We compared MRD status and clinical outcome with a matched group of FLT3 wildtype AML (n = 128). Both groups were treated according to intensive EORTC/GIMEMA protocols. MRD was measured by MFC at the post‐consolidation timepoint. Patients were defined as MRD‐negative, when obtaining a residual leukemic cells (RLCs) count below the threshold of 3.5x10–4 (0.035%).Results:Overall median age was 47 (range 17–72). The 2 cohorts were balanced in terms of age and sex distribution. In the FLT3 mutated group, 22 out of 37 (59%) cases carried a concomitant NPM1 mutation vs 32 out of 124 (26%) of FLT3 wildtype ones (p &lt;0.001). Furthermore, FLT3 mutation was significantly associated with a WBC count &gt;50x109/L (20/39, 51%) vs 30/128 (23%) of those FLT3 wildtype (p &lt; 0.001). Post remission treatment allocation was different between FLT3 mutated patients as compared to. FLT3 wildtype ones; 16 out of 39 (41%) FLT3 mutated patients were submitted to allogenic stem cells transplantation (ASCT) as compared to 34 out of 128 (27%) FLT3 wildtype ones (p = 001). At the post‐consolidation time‐point, MRD negativity rate was significantly lower in FTL3 mutated patients (4/39, 10%) as compared to those FLT3 wildtype (40/128, 31%), (p = 0.009). In particular, 32 out of 35 (91%) FLT3 mutated patients were above the ELN recommended threshold of positivity (0.1%) and 11/35 (31%) were above 1% of RLC.Among FLT3 mutated patients, OS was significantly longer for patients obtaining MRD‐negativity as compared to those who did not (67% vs. 31%, p = 0.9). As for as DFS, we observed the same difference for MRD negative patients vs. MRD positive ones (67% vs. 29%, p = 0.8). The negative impact of MRD was proportional to the amount of RLC at post‐consolidation time‐point (Figure 1) (p = 0.045). However, among FLT3 mutated patients, ASCT was the only post remission treatment allowing a prolonged OS to be achieved as compared to autologous SCT or standard chemotherapy (4‐years OS 63% vs. 0% vs. 15%, p = 0.019, respectively).Summary/Conclusion:In conclusion, MRD as measured by MFC is a biomarker of response also in FLT3 mutated patients. In these patients, ASCT delivery is associated with a satisfactory long term outcome, however a longer duration of response can be pursued by administering FLT3 inhibitors before or after transplant, in order to improve the quality of remission and prevent leukemic recurrence.image

PS1061 ELDERLY PATIENTS WITH DE NOVO OR SECONDARY AML HAVE COMPARABLE OUTCOMES AFTER INTENSIVE TREATMENTS INCLUDING HIGH DOSE (HD) CYTARABINE AND AUTOLOGOUS (AUTO) OR ALLOGENEIC (ALLO) TRANSPLANTATION (SCT)

Background:secondary acute myeloid leukemia (s‐AML) represent a high‐risk AML subset with poor outcome, worse than denovo AML. Of note, most patients (pts) are older than 60 years and have comorbidities, frequently tailoring under‐powered treatment. At our center, we offer intensive treatments to selected elderly AML pts, according to patient's fitness and AML prognostic risk factors. Here we present data of our denovo and secondary AML pts treated during the last 18 yrs.Aims:to compare outcomes of denovo AML and sAML pts, older than 60, after intensive treatments at our centerMethods:retrospective analysis of data from 123 pts with untreated AML, 66 sAML and 57 denovo AML, diagnosed between 10/2001–1/2019, median age 68 y (61–78) in both groups. Criteria for pts selection to receive intensive treatments: PS (ECOG) ≤ 2, renal and hepatic parameters &lt; 2 times normal values, no active infections and cardiac ejection fraction &gt; 50%. Categorical data were compared by the Fisher's exact test, overall survival (OS) and disease free survival (DFS) were analysed and compared by the Kaplan‐Meier method and Log‐Rank Test, relapse incidence by the Gray Test.Results:distribution of pts in the genetic risk groups (ELN2017, 70 pts evaluable) significantly differed only for pts in the favourable one: 1 sAML patient, 13 denovo AML pts, p = 0.0003. Induction and post remission standard (CHT) and high dose (HDARAC) cycles of chemotherapy are reported in tab1. sAML pts received more HDARAC cycles than denovo AML pts. CR rate: sAML 70% (46 pts), denovo AML 72% (41 pts), p = ns. CR after first induction (C1): sAML 53% (35 pts), denovo AML 54% (31 pts), p = ns. In sAML pts only, CR rate after C1 with HDARAC was significantly higher than with CHT: 64% (30 pts) and 26% (5 pts), respectively, p = 0.0072. Second induction was HDARAC for most pts not in CR after C1. TRM of the induction phase: sAML 3% (2 pts) and denovo AML 10.5% (6 pts), p = ns. Further 6 pts obtained the CR after alloSCT, 5 sAML and 1 denovo AML. Relapse incidence (RI): @3y sAML 38 ± 12% and denovo AML 48 ± 14%. Overall survival (OS): median, sAML 515 days and denovo AML 389 days, @3y sAML 37% and denovo AML 31%, p = ns. Disease free survival (DFS): median, sAML 470 days and denovo AML 313 days, @3y sAML 30% and denovo AML 22%, p = ns.TableSummary/Conclusion:CR rate and long term survival were encouraging and comparable in the two studied groups of pts. More intensive induction with HDARAC in sAML than denovo AML pts was the only significantly different variable in the two groups. HDARAC probably induced a more profound remission in our pts overcoming the unfavourable biologic characteristics of sAML. Of note, intensive post‐remission treatments, including auto and allo SCT, proved feasible either after CHT either after HDARAC induction in our elderly pts. In conclusion, we suggest to consider initial treatment with HDARAC for sAML pts, fit for intensive treatments.image

PS1545 IMPACT OF MOLECULAR RESPONSE ON SURVIVAL AMONG ALLOGENEIC STEM CELL TRANSPLANTATION RECIPIENTS WITH B‐LYMPHOBLASTIC LEUKAEMIA WITH BCR‐ABL1

Background:Assessment of minimal residual disease (MRD) has emerged as a prognostic tool for patients with acute lymphoblastic leukaemia (ALL). In patients with B‐Lymphoblastic Leukaemia with BCR‐ABL1, MRD assessment can identify patients more likely to benefit from stem cell transplantation (SCT) in first complete remission (CR1). However, the impact of achieving complete molecular response (CMR) in B‐Lymphoblastic Leukaemia with BCR‐ABL1 remains undefined. The addition of immunotherapies and tyrosine kinase inhibitors (TKI) to standard chemotherapy has led to deeper molecular responses, as measured by quantitative polymerase chain reaction of the BCR‐ABL1 transcript, and are associated with improved outcomes. MRD was monitored after induction time point (TP)1, consolidation phase at week 16 (TP2) and end of therapy or pre transplant (TP3).Aims:The aim of this study was to investigate the prognostic impact of achieving a complete molecular response (CMR) among our adult B‐Lymphoblastic Leukaemia patients with BCR‐ABL1 with the treatment outcomes in Hospital Ampang, the national tertiary referral centre in Malaysia.Methods:Patients above 12 years of age diagnosed at Hospital Ampang between 2007 and 2017 were included in this study. Major molecular response MMR was defined as BCR‐ABL1:ABL1 ratio ≤0.1% on the International Scale for p210 BCR‐ABL1 or a 3‐log reduction in transcripts for p190 BCR‐ABL1. Overall survival (OS) was analysed using Kaplan‐Meier survival function, calculated from the time of treatment initiation till death and divided into 2 groups of BCR‐ABL1:ABL1 ratio ≤0.1% and BCR‐ABL1:ABL1 ratio &gt;0.1%. The different groups were compared using log‐rank test.Results:A total of 96 adult patients were identified with median age of diagnosis of 37.5 years old (range from 14 to 69 years old), female predominance (56%), and majority Malay ethnicity (50%). At the time of analysis, 33 (34.4%) patients were alive. The median overall survival (OS) of this cohort was 16.8 months (95%CI: 12.0; 20.9). Median OS was not significantly different (p &gt; 0.05) between those who had achieved major molecular response (MMR) (BCR‐ABL1:ABL1 ratio ≤ 0.1) and those who did not (20.4 months vs 16.8 month) at TP1, those who had achieved MMR at TP2 (35.7 months vs 17.5 months) and those who had additional myeloid markers (13.1 months vs 25.3 months). Median OS was significantly different between patients who achieved MMR at TP3 as compared to those who did not (77.0 months vs 20.4 months, p = 0.006). The risk of dying is 3 times higher for those who did not achieved MMR at TP3 (hazard ratio = 3.0, 95%CI: 1.97; 6.70, p = 0.009) compared to those who had MMR.Summary/Conclusion:Achievement of MMR at TP3 prior to allogeneic stem cell transplantation is associated with superior survival outcomes. Prospective trials using MRD‐based risk stratification and to guide treatment decision for B‐Lymphoblastic Leukaemia patients with BCR‐ABL1 may elucidate the optimal post remission management of these patients.

PS981 LONG TERM AML SURVIVORS HAVE INCREASED MORTALITY AND HIGH PREVALENCE OF CLONAL HEMATOPOIESIS

Background:Acute myeloid leukemia (AML) is defined by the accumulation of immature blasts in the bone marrow (BM) resulting, if left untreated, in acute BM failure. While AML presents in an acute form, it is clear today that most AML cases are preceded by a long phase of age related clonal hematopoiesis (ARCH) with almost no symptoms. The clinical and molecular trajectories of AML both before and after diagnosis are highly predictable. Recent studies identified the high risk individuals destined to evolve from ARCH to AML based on blood counts parameters (mainly red cell distribution width (RDW)) and molecular attributes such as clone size and the number of ARCH defining events. Most AML patients will achieve complete remission after induction chemotherapy, however most will relapse within a median time of 11 months despite post remission consolidation or bone marrow transplantation (BMT). A small fraction of AML patients will maintain at long term remission (LTR).Aims:The course of AML from ARCH to relapse is well characterized both clinically and molecularly, however, this information is missing for long term AML survivors, specifically for AML patients who did not receive BMT. The fact that AML has a long chronic history before its acute presentation might suggest that a recovery from the acute phase will not necessary result in resetting the hematopoietic system but rather to turn it back to its chronic phase before AML presentation.Methods:To answer the question whether preleukemic events are still present at LTR and what important clinical implications it might have, we studied morbidity, mortality and molecular structure among two unique LTR cohorts. One cohort is the electronic health records (HER) of 4.2 million individuals covering over 15 years of follow up and include 61 LTR survivors who did not undergo BMT (LTSnoBMT). The second cohort which contains molecular data, included analysis of genetic variation in 30 LTR cases at diagnosis and LTR, and was compared to a group of lymphoid malignancies patients at remission.Results:We found that the mortality among LTSnoBMT 10 years after diagnosis was 20%&gt;50% higher in comparison to controls. In addition, several lab results were different between the LTSnoBMT and controls including higher red cell distribution width (RDW) among older (&gt;55) LTSnoBMT. Recent studies found a correlation between high RDW and mortality among individuals carrying age related clonal hematopoiesis (ARCH) mutations. We also found that ARCH defining events were significantly more prevalent among LTSnoBMT in comparison to controls (63% vs 37% p = 0.039). Furthermore of the ARCH defining events among the LTSnoBMT 62% were recurrent AML variants as oppose to 21% among the controls (p = 0.002). Of the recurrent mutations IDH1/2 were the most common mutations and 2 out of 7 IDH1/2 cases experienced a late relapse (Figure 1).Summary/Conclusion:Altogether, even after the sustainable eradication of the malignant clone, the hematopoietic system/microenvironment does not normalize (abnormal blood counts, high prevalence of ARCH and higher mortality).imageThese results suggest that AML at LTR is a unique situation and that this group of patients are not fully recovered and should be further studied and treated.

Haplo-HSCT Is Superior to Chemotherapy for Standard Risk ALL in CR1—Results of Prospective Multicenter Trial (NCT02042690)

Background In the present prospective multicenter trial (NCT02042690), we investigated whether haplo-HSCT has a favorable impact on survival as post remission treatment for standard risk acute lymphoblastic leukemia (ALL) patients in the first complete remission (CR1) by comparing with chemotherapy alone. Methods £°Inclusion criteria of ALL:(1) age 18 to 39 years; (2) without high-risk features, which consisted of elevated WBC count(>30 *109/L for B cell lineage or >100 *109/L for T cell lineage), or high-risk cytogenetic abnormalities, determined according to the National Comprehensive Cancer Network 2013 guidelines; and (3) achieving CR after 1 to 2 cycles of induction. Subjects without a suitable HLA matched sibling (MSD) or HLA-matched unrelated donor (iÝ8/10 URD) after 2 cycles of consolidation (Hyper-CVAD B/A*1) were eligible for haplo-HSCT or further chemotherapy (Hyper-CVAD B/A*3). Landmark analysis (4 months after CR1) was used when comparing the outcomes of patients receiving haplo-HSCT vs. chemotherapy. A propensity score (PS) was calculated using multivariable logistic regression for each individual. The hazard ratios (HRs) for Leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse(CIR), and nonrelapse mortality(NRM) were adjusted with PS. Results Newly diagnosed standard risk ALL patients meeting inclusion criteria (n=112) were consecutively enrolled at 5 centers including Peking University Peoplei¯s Hospital, Peking Union Hospital, Wuhan Union Hospital, First Hospital of Soochow University and General Hospital of PLA and between July 2014 and June 2017, with median follow-up 24.6 months. Patients were excluded in final analysis: 1) early relapse (n=6) within 4 months after CR1; 2) MSD-HSCT (n=16) or URD-HSCT (n=1). The remaining patients (n=89) either received haplo-HSCT (n=49) or chemotherapy (n=40). The 2-year LFS (70.5 [54.2-81.9]% vs 41.4[25.9-56.2]%, p=0.0073) and 2-year OS (81.3 [65.5-91.4]% vs 51.2[33.8-66.1]%, p=0.0073) of the Haplo-HSCT group was significantly higher than the chemotherapy group. In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs chemotherapy) was an independent risk factor affecting the LFS (HR 0.388, 95% CI 0.172-0.873, P=0.022), OS (HR 0.346, 95% CI 0.156-0.140-0.853, P=0.003) and CIR(HR 0.247, 95% CI 0.098-0.624, P=0.003); Positive minimal residual disease after the first consolidation was an independent risk factor for LFS (HR 2.162, 95% CI 0.973-4.803, P=0.027) and CIR (HR 3.667, 95% CI 1.445-9.302, P=0.006). Diagnosis (T vs B) was an independent risk factor for OS(HR2.267, 95% CI 1.493-3.442, P=0.021). Conclusions Our results suggest that Haplo-HSCT is superior to chemotherapy alone as post-remission treatment for in adult patients (age 18-39) with standard risk ALL in CR1.

The Choice of Induction Regimen Affects Post Remission Survival of Acute Myelogenous Leukemia (AML) Patients with Intermediate or Poor Risk Disease

The fludarabine, high dose cytarabine and G_CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The MRC trial 15 compared 2 induction courses of FLAG-Ida regimen to 3+7 (anthracycline plus cytarabine) regimens with etoposide (ADE) and found a higher relapse free survival among patients receiving FLAG-Ida. The findings of the MRC AML 15 trial are not widely applied in the United States as many experts use one course of induction followed by consolidation if patients achieve remission. The impact of choice of induction regimen on post remission survival in non-favorable risk AML patients remains unclear. To address this question, we assessed outcomes of 306 consecutive AML patients between aged 18 to75 years, with non-favorable NCCN risk who were received initial treatment at our center between January of 2009 and July of 2017 with either 3+7 (n=88) or FLAG+/-Ida (n=218). Our center's algorithm is to offer allogeneic HSCT as a consolidative therapy to all AML patients with non-favorable risk in CR1 who are considered transplant candidates. Patient characteristics were as follows: Median age 58(19, 75), male 55%, FLT-3 ITD positive 12%, NCCN risk ( intermediate 49%, poor 51%) and normal cytogenetics 45%. Baseline characteristics were similar between the two treatment groups with FLAG+/-Ida being younger at time of diagnosis (59 vs 66 years, P<0.001). A total of 240 (78%) patients achieved CR 1 after 3+7 (n=67, 76%) or FLAG+/-Ida (n=167, 79%) with no difference in the rate of achieving remission between the two groups. Patients in the FLAG-Ida group were more likely to achieve remission after one course of induction (74% vs 62%, p<0.001) and had a faster time to get into CR (30 days vs 37.5, p<0.001) compared to 3+7. CR was achieved in 84% and 73% of patients with intermediate and poor NCCN risk disease respectively. HSCT was performed in 172 patients accounting for 72% of the 240 patients who achieved CR post induction without any significant difference in transplant rates between FLAG+/-Ida and 3+7. The time from diagnosis to transplant was significantly shorter among CR patients after FLAG+/-Ida compared to 3+7 (FLAG+/- Ida 115 days vs 144 days for 3+7, p<0.001). After a median follow up of 41 months for patients achieving CR, the 3 year post remission OS and DFS was significantly better for patients receiving FLAG-Ida at 54% and 49% compared to 39% and 32% for patients receiving 3+7 respectively( P= 0.01 for both endpoints). In multivariate analysis, we analyzed factors associated with OS and DFS since achieving CR1 including age at CR1 (≤49, 50-64, ≥65), gender, race, NCCN risk, induction regimen, number of cycles to CR1, HSCT (yes, no) and year of CR1. HSCT was modelled as a time dependent covariate. A forward stepwise algorithm was implemented and variables were selected if p value was less than 0.05. Factors associated with r post remission survival included age at CR1 (≤49 vs50-64, HR 0.59, p=.02; ≤49 vs ≥65 HR 0.46, p=0.001), NCCN risk (intermediate vs poor HR 0.54, p<0.001), induction regimen (FlAG+/-Ida vs 3+7 HR 0.62, p=0.01) and receiving HSCT (yes vs no HR 0.68, p=0.02). Factors affecting DFS from time of CR also included age, NCCN risk, induction regimen (FlAG+/-Ida vs 3+7 HR 0.68, p=0.028) and receiving HSCT. This single center analysis shows that among patients with non-favorable risk AML, achieving CR after FLAG+/-Ida has better post remission survival than 3+7. This may be partially explained by the faster time to achieve CR and faster time to HSCT in the FLAG+/- Ida group. DisclosuresSolh:Amgen: Speakers Bureau; Celgene: Speakers Bureau; ADC Therapeutics: Research Funding.

Immunophenotypic Assessment of Minimal Residual Disease in Younger Acute Myeloid Leukemia Patients Is Highly Predictive of Outcome

Introduction: Mainstay of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR) as evident by less than 5% blasts. Post remission strategies then focus on either consolidation chemotherapy or allogeneic bone marrow transplantation (aBMT). However, not all patients by this remission criterion achieve long term remission and a subset of patients' relapse. This relapse originates from further expansion chemoresistant clones. Detection of minimal residual disease (MRD) following chemotherapy, early in the course of treatment, is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse as seen in ALL. Here, we describe assessment of immunophenotypic MRD using a 10-colour two tube assay and a combination of difference from normal and leukemia associated immunophenotype (LAIP) approach in patients of adult AML.Methods: We accrued 310 patients of adult (>18 years) AML, other than with t(15;17), over a 66-month period (1st July 2012- 31st December 2017) after obtaining informed consent. All patients received standard induction chemotherapy. MRD testing was done post induction and after first consolidation with high dose cytarabine. Patients accrued from 1st July 2012 to 28th February 2015 (85 patients) were processed using a three tube 8 colour MRD assay. Subsequently samples of 225 patients were processed using a two tube 10 colour MRD assay. Identical panel was used for diagnostic sample, post induction and post consolidation. 500,000 events were acquired per tube with the 3-tube assay and 1.6 million events per tube obtained per tube with the 2 tube, 10 colour assay. Analysis of MRD was done using Kaluza 1.3 by a combination of difference from normal approach that focused on the development of Myeloid progenitors to mature cells and LAIP approaches. Cytogenetic studies by conventional karyotyping and FISH was done as per NCCN version 2 2014 recommendations. Patients were classified into favorable, intermediate and poor cytogenetic risk. The presence of FLT3-ITD, NPM1 and CEBPA mutations were detected by a fragment length analysis-based assay. Overall survival (OS) was calculated from date of diagnosis to time of last follow up or death. Relapse free survival (RFS) was calculated from date of CR till time to relapse or death or last follow up if in CR. Results of the MRD assays, cytogenetic and molecular risk groups were analyzed for their impact on OS and RFS using log rank test.Results: The median age of entire cohort was 33 years (M : F = 1.6 : 1). Based on cytogenetics, 35.1% were classified as favorable risk whereas 52.5% and 12.2% were intermediate and poor risk respectively. FLT3-ITD, NPM1 and CEBPA mutations were detected in 21.9%, 29.0% and 7.7% of patients respectively. Post induction MRD was assessed in 298 patients of which 114 (38.3%) had detectable residual disease (range 0.004-22.6%, median:0.9%). Post consolidation MRD was assessed in 186 patients of which 49 (26.4%) were MRD positive (range 0.002-19.8%, median: 0.37%).The 3 year OS, RFS and median RFS of the entire cohort was 59.0%, 44.8% and 18.7 months respectively. Poor risk cytogenetics as expected was predictive of inferior OS (median OS = 14.6 months vs not reached, p=0.05) as well as RFS (median RFS = 9.3 months vs 18.6 months, p=0.003 respectively). FLT3, NPM1 and CEBPA mutations were not informative as predictors of outcome.The presence of MRD at post induction time point predicted an inferior OS [(p=0.08), HR:1.53; 95% CI (0.93-2.51)] & RFS [(p=0.0002), HR:2.14; 95% CI (1.4-3.3)] as compared to the MRD negative group. Similarly, patients harboring MRD at the end of consolidation had an inferior OS [(p=0.04), HR:1.83; 95% CI (0.94-3.6)] & RFS [(p=0.02), HR:1.79; 95% CI (1.04-3.09)] as compared to the MRD negative group. On multivariate analysis post induction FCM MRD emerged as the most important independent prognostic factor predictive of inferior outcome for RFS [(p=0.01); HR:2.14; 95% CI (1.17 - 3.4)] followed by poor cytogenetic risk [(p=0.05); HR:1.8; 95% CI (1.0 to 3.26)].Conclusion: Our data demonstrates that MRD by flow cytometry at end of induction as well as consolidation are important prognostic factors together with known factors such as high risk cytogenetics. AML MRD is a very useful guide for post remission strategies in AML and should be incorporated into routine treatment algorithms. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Single-Cell Mass Cytometry Characterizes Phenotypic and Functional Heterogeneity in Acute Myeloid Leukemia at Diagnosis, in Remission and Relapse

Single-Cell Mass Cytometry Characterizes Phenotypic and Functional Heterogeneity in Acute Myeloid Leukemia at Diagnosis, in Remission and Relapse

Minimal Residual Disease in Acute Myeloid Leukemia Using a Difference from Normal Approach Is Predictive of Outcome

Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML), other than acute promyelocytic leukemia, is induction with a goal to achieve morphological complete remission (CR) as evident by less than 5% blasts. Post remission strategies then focus on either consolidation chemotherapy or allogeneic bone marrow transplantation (aBMT). However, not all patients by this remission criterion achieve long term remission and a subset of patients relapse. This relapse originates from further expansion chemoresistant clones. Detection of minimal residual disease (MRD) following chemotherapy, early in the course of treatment, is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse. Here, we describe assessment of immunophenotypic MRD using a 10-colour two tube assay and a "difference from normal" approach.Methods: We accrued 100 consecutive patients of adult (>18 years) AML, other than with t(15;17), over a 14 month period after obtaining informed consent. All patients received "3+7" induction therapy with daunorubicin and cytarabine. If patients were in morphological CR at end of induction, they either received 3 courses of 12-18 gm/m2 high dose cytarabine (HiDAC) or aBMT if feasible.MRD testing was done at two time points, post induction and post 1st Cycle HiDac using a two tube 10 colour assay. (CD15, CD13, CD19, CD34, CD56, CD7, CD45, CD11b, HLA-DR, CD117, CD14, CD123, CD64, CD33, CD36 & CD38). A minimum of one million events were acquired per tube on a Navios flow cytometer. Identical panel was used at MRD time points as well as on the diagnostic sample. Analysis of MRD was done using Kaluza 1.3 by a difference from normal approach that focused on the development of progenitors to monocytes. Conventional karyotyping and FISH was done as per standard recommendations and patients were classified into favorable, intermediate and poor cytogenetic risk. The presence of FLT3-ITD, NPM1 and CEBPAmutations was detected by a fragment length analysis based assay. Overall survival (OS) was calculated from start of induction therapy to time of last follow up or death. Relapse free survival (RFS) was calculated after achieving of 1st remission (CR) till relapse or death or last follow up if in CR. Results of the MRD assays, cytogenetic and molecular risk groups were analyzed for their impact on OS and DFS.Results: A total of 100 AML patients were treated and followed up over a 14 month period. Based on cytogenetics, 36.7% were classified as favorable risk whereas 54.1% and 9.2% were intermediate and poor risk respectively. FLT3-ITD, NPM1 and CEBPA mutations were harbored by 9%, 19% and 8% of patients respectively. The OS was 63% and RFS was 50% with a median follow up of 6 months. Of these, 24 had induction death and 17 had refractory disease. Post induction MRD was assessed in 70 patients of which 25 (35.7%) had detectable residual disease (range 0.02-55%, median:1.5%). Post consolidation MRD was assessed in 49 patients of which 14 (28.6%) were MRD positive (range 0.002-7.7%, median: 0.03%). Favorable risk cytogenetics was predictive of better RFS (p=0.007) but not OS. FLT3-ITD positive status was associated with worse OS (p=0.01) but not RFS. Patients harboring MRD at the end of induction were associated with worse OS (p=0.08) & RFS (p=0.04), whereas post consolidation positive MRD status was strongly associated with inferior RFS (p=0.04).Conclusion: Our data is in agreement with other studies that determination of immunophenotypic MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post remission strategies in AML and should be incorporated into routine treatment algorithms.Acknowledgments: Dr Nikhil Patkar is supported by the Wellcome Trust - DBT / India Alliance through an Intermediate Fellowship for Clinicians and Public Health Researchers. This research is supported through an India Alliance grant (IA/CPHI/14/1/501485). DisclosuresPatkar:Wellcome Trust-DBT India Alliance: Research Funding.