scholarly journals Allotransplants for Patients 65 Years or Older with High-Risk Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4667-4667
Author(s):  
Paul Lin ◽  
Lauren Westfall Veltri ◽  
Katy Rezvani ◽  
Betul Oran ◽  
Sairah Ahmed ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Risk Group ◽  
Morphological Evidence ◽  
Consolidation Chemotherapy ◽  
Medical Event ◽  
History Of

Abstract Outcome of persons >65 years with acute myeloid leukemia (AML) is poor. Allogeneic transplant can cure some of these patients but is associated with substantial transplant-related mortality (TRM) and high relapse risk. We analyzed 185 consecutive patients >65 years with high-risk AML between 2010 and 2015 who had measurable residual disease (MRD) and molecular risk assessments and who received myeloablative conditioning (MAC, n=42) or reduced-intensity conditioning (RIC, n=143) and a transplant from an HLA-identical sibling (n=66) or a 10/10 loci HLA-matched unrelated donor (MUD, n=119) in order to identify patients who would benefit from allotransplant. MRD was assessed by flow cytometry in bone marrow samples. AML cytogenetic and molecular risk were defined using the 2017 European Leukemia Net genetic risk stratification. The patients who were MRD-negative at time of transplant had a better 2-year cumulative incidence of relapse (CIR 17.6%) and a 2-year overall survival (OS, 69.4%) as compared to the patients in remission but MRD-positive (55.6% CIR, 21.5% OS) or the patients who had morphological evidence of leukemia prior to transplant (48.7% CIR, 19.9% OS), (p<0.0001). Multivariate analysis for 2-year CIR showed that having detectable leukemia at time of SCT (defined as MRD-positive or morphological evidence of leukemia) (HR=14.5, CI=3.4-61.4, p<0.0001), having received <3 cycles of chemotherapy prior to SCT (HR=1.8, CI=1.1-2.8 p=0.01), and high-risk genetics were independent predictors of relapse. However, high-risk genetics only had a deleterious effect on outcomes for MRD-negative patients (HR=9.4, CI=2.0-43.6, p=0.004), and did not affect the outcome of patients with detectable leukemia (HR=1.1, CI=0.7-1.9, p=0.61). Patients who received RIC (Flu-Mel-RIC or Bu-Flu-RIC) or MAC (Bu-Flu-MAC) had similar proportion of MRD-negative patients (p=1.0). However, MRD-negative patients who received Flu-Mel-RIC had a superior OS than patients who received Bu-Flu-RIC (adjusted HR=1 vs 5.3, p=0.02) or patients who received Bu-Flu-MAC (HR=1 vs 5.093, p=0.04), which is explained by a significantly lower relapse rate in patients receiving Flu-Mel-RIC (adjusted HR=1 vs 4.8, p=0.03) and a significantly lower TRM as compared to patients receiving Bu-Flu-MAC (adjusted HR= 5.1, p=0.01). Patients who had major medical complications (MMC), defined as a medical event requiring admission to the intensive care unit for ventilatory or inotropic support or a medical event that prolonged the patient hospitalization for more than 2 weeks, during induction or consolidation chemotherapy preceding the transplant, had a higher day +100 mortality (30.6% vs 6.0%, p<0.0001), 2-year TRM (55.6% vs 16.8%, p<0.0001) and lower 2-year OS (8.3% vs 44.6%, p<0.0001). Multivariate analysis for 2-year OS showed that history of delayed hematological recovery during induction or consolidation chemotherapy prior to transplantation (HR=1.5, CI=1.0-2.3, p=0.04), high risk genetics (HR=1.8 CI:1.2-2.6, p=0.006), donor-recipient HLA-DRβ3/4/5-DP mismatch (HR=2.2, CI=1.3-3.6, p=0.001), history of cardiovascular disease (HR=1.7, CI=1.1-2.6, p=0.02) were independent predictors for OS. Other variables such as secondary leukemia, CMV sero-status, FEV1 or creatinine clearance prior to SCT, sex mismatch, ABO group mismatch, donor type, or stem cell source did not have a significant impact on OS or TRM. Outcomes were also similar between patients transplanted in CR1 or in ≥ CR2 or in CR or CRi. We sought to identify those patients who may clearly benefit from a SCT. To that end, we classified patients according to the MRD status prior to transplantation and the presence or absence of the other prognostic factors identified in the multivariate analysis. As seen in the Figure, the High risk group which includes patients with detectable leukemia and >1 additional adverse prognostic factors (or a MMC), had a 2-year OS of 7.7% (CI=3.1-17.8). In comparison, the Low risk group which includes MRD-negative patients with ≤3 other prognostic factors (and no MMC), had a 2-year OS of 76.2% (CI=63.3-85.6). Finally, the Intermediate risk group which constituted the remaining patients, had a 2-year OS of 32.2% (CI=22.1-44.3, p<0.00001). These data indicate the possibility to identify persons >65 years with high-risk AML likely to benefit from an allotransplant. Figure. Figure. Disclosures Rezvani: Affirmed GmbH: Research Funding. Oran:ASTEX: Research Funding; Celgene: Consultancy, Research Funding; AROG pharmaceuticals: Research Funding. Shpall:Affirmed GmbH: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Varying Importance of Prognostic Factors in Subgroups of Myelodysplastic Syndromes Defined by Blast Count, Cytogenetic Risk Group, or WHO Classification.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2776-2776
Author(s):  
Andrea Kuendgen ◽  
Corinna Strupp ◽  
Kathrin Nachtkamp ◽  
Barbara Hildebrandt ◽  
Rainer Haas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Univariate Analysis ◽  
Risk Groups ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Blast Count

Abstract Abstract 2776 Poster Board II-752 Introduction: We wondered whether prognostic factors have similar relevance in different subpopulations of MDS patients. Methods: Our analysis was based on patients with primary, untreated MDS, including 181 RA, 169 RARS, 649 RCMD, 322 RSCMD, 79 5q-syndromes, 290 RAEB I, 324 RAEB II, 266 CMML I, 64 CMML II, and 209 RAEB-T. The impact of prognostic variables in univariate analysis was compared in subpopulations of patients defined by medullary blast count, namely <5%, ≥5% (table), ≥10%, and ≥20% (not shown), as well as 3 subpopulations defined by the cytogenetic risk groups according to IPSS (table). Multivariate analysis of prognostic factors was performed for cytogenetically defined subgroups and WHO-subtypes. Results: Strong prognostic factors in all blast-defined subgroups were hemoglobin, transfusion dependency, increased WBC, age, and LDH. However, all variables became less important in patients with ≥20% blasts (RAEB-T) and increased WBC was rare. Platelet count and cytogenetic risk groups were relevant in patients with <5%, ≥5%, and ≥10% marrow blasts, but not in RAEB-T. Marrow fibrosis was important in patients with <5% or ≥5% blasts, but not ≥10%. Gender and ANC <1000/μl were significant only in patients with a normal blast count. Furthermore, we looked for the effect of the karyotypes, relevant for IPSS scoring (-Y, del5q, del20q, others, del7q/-7, complex), and found a comparable influence on survival, irrespective whether patients had < or ≥5% marrow blasts. In subpopulations defined by cytogenetic risk groups, several prognostic factors were highly significant in univariate analysis, if patients had a good risk karyotype. These included hemoglobin, sex, age, LDH, increased WBC, transfusion need, and blast count (cut-offs 5%, 10%, and 20%). In the intermediate risk group only LDH, platelets, WBC, and blasts were significant prognostic factors, while in the high risk group only platelets and blast count remained significant. Multivariate analysis was performed for the cytogenetic risk groups and for subgroups defined by WHO subtypes. The analysis considered blast count (</≥5%), hemoglobin, platelets, ANC, cytogenetic risk group, transfusion need, sex, and age. In the subgroup including RA, RARS, and 5q-syndrome, LDH, transfusion, and age in descending order were independent prognostic parameters. In the RCMD+RSCMD group, karyotype, age, transfusion, and platelets were relevant factors. In the RAEB I+II subgroup, the order was hemoglobin, karyotype, age, and platelets, while in CMML I+II only hemoglobin had independent influence. In RAEB-T none of the factors examined was of independent significance. Looking at cytogenetic risk groups, in the favorable group, several variables independently influenced survival, namely transfusion, blasts, age, sex, and LDH (in this order). Interestingly, in the intermediate and high risk group, only blast count and platelets retained a significant impact. Conclusion: Univariate analysis showed prognostic factors (except ANC) included in IPSS and WPSS are relevant in most subgroups defined by marrow blast percentage. However, they all lose their impact if the blast count exceeds 20%. Regarding cytogenetic risk groups, several prognostic factors lose their influence already in the intermediate risk group. This underscores the prognostic importance of MDS cytogenetics. Multivariate analysis showed MDS subpopulations defined by WHO types also differ with regard to prognostic factors. In particular, CMML and RAEB-T stand out against the other MDS types. Disclosures: Kuendgen: Celgene: Honoraria. Hildebrandt:Celgene: Research Funding. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials. Germing:Novartis, Celgene: Honoraria, Research Funding.

scholarly journals Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3433-3433
Author(s):  
Caitlin Siebenaller ◽  
Madeline Waldron ◽  
Kelly Gaffney ◽  
Brian P. Hobbs ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Smoking Status ◽  
Consolidation Therapy ◽  
Peripheral Vascular ◽  
Consolidation Chemotherapy ◽  
Advisory Committees ◽  
History Of ◽  
Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Survival Improvement Of Secondary Acute Myeloid Leukemia Over Time: Experience From 962 Patients Included In 13 EORTC-Gimema-HOVON Leukemia Group Trials

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 829-829 ◽  
Author(s):  
Safaa M. Ramadan ◽  
Stefan Suciu ◽  
Marian J.P.L. Stevens-Kroef ◽  
Roelof Willemze ◽  
Sergio Amadori ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Malignant Disease ◽  
Risk Group ◽  
Toxic Exposure ◽  
Secondary Acute Myeloid Leukemia ◽  
History Of ◽  
Over Time ◽  
Acute Myeloid

Abstract Background Secondary acute myeloid leukemia (sAML) describes patients (pts) with a history of malignant or non-malignant disease or AML secondary to environmental, occupational or therapeutic exposures. They are generally associated with poor outcome despite the use of intensive treatments. The impact of clinical features and type of treatment on pts' outcome is still not well established. In the current analysis we evaluated sAML pts who were treated in 13 EORTC collaborative trials conducted between May 1986 and January 2008. sAML pts in the database were pooled to characterize clinical features of the disease and evaluate changes in survival over these years (yrs). Method Main selection criteria were AML with bone marrows blasts ≥20% and documented history of prior malignancy, non-malignant disease and/or toxic exposure. AML-M3 and MDS without confirmed diagnosis ≥2 months before AML were excluded. All pts were eligible for standard treatment. Induction regimens were anthracycline and AraC based: 7+3, including etoposide, intensified with high dose (HD)-AraC randomized to standard doses (SD) in younger (AML12) or gemtuzumab ozogamicin in elderly pts. Consolidation regimens were age adapted. In mid-1980s, autologous transplant was tested vs a 2nd consolidation cycle (AML8A) in pts ≤45 yrs and thereafter used systematically in pts ≤60 yrs without available donor. Allogeneic transplant (Allo-SCT) was offered to pts ≤46 yrs with HLA-compatible sibling since mid-1980s and expanded in the last decade to pts up to 59 yrs. Selected pts were divided into 3 sAML cohorts, cohort A after MDS, cohort B after other malignant diseases and cohort C after non-malignant conditions and/or toxic exposure. Results Of 8858 pts enrolled in the 13 evaluated studies, 962 were sAML. Median age was 63 yrs (range 16-85), 413 were young (≤60 yrs) and 549 were elderly (≥61 yrs); 54% were males. Cohort A consisted of 509 pts (median age 64 yrs), cohort B of 362 pts (median age 59 yrs) and cohort C of 91 pts (median age 61 yrs). In cohort B, breast cancer (24%) and lymphoma (14%) were the most frequent primary tumors. Autoimmune diseases represented 22% of non-malignant conditions. In young pts, complete remissions (CR/CRi) rate was 59%; 55% in SD-AraC vs 89% in HD-AraC treated pts. Allo-SCT in CR1 was performed in 21% of all pts. The Allo-SCT rate increased from 5% before 1990, 20% in 1990-1999 to 25% from 2000 (20% in SD-AraC vs 31% of HD-AraC treated pts). CR/CRi was achieved in 45% of elderly pts. Median follow-up was 6 yrs. Median overall-survival (OS) was 14.5 months in young and 9 months in elderly pts. The 5-yr OS was 28% and 7% respectively. Five-yr OS was 11% in cohort A and 22% in both cohort B and C. Treatment outcome of younger pts according to disease features and treatment type over time in cohort A and B are detailed in table 1 & 2. Using Cox model stratified by cohort age, gender, WBC, risk group, year of treatment and HD-AraC were independent prognostic factors for OS. In the AML12 study, compared to denovo pts, sAML pts ≤45 yrs had worse outcome if treated with SD-AraC whereas a better OS was seen if treated with HD-AraC. In elderly pts only the good/intermediate risk group of cohort B had a relatively better 5-yr OS (15%). Conclusions The outcome of sAML in younger pts has improved over the yrs in parallel with HD-AraC introduction in induction of remission. HD-AraC should be considered for younger pts with sAML. Disclosures: Ramadan: Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Suciu:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Meert:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. de Schaetzen:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other Other.

Prognostic Factors of Infections and Effect of Primary Anti-Infectious Prophylaxis in MDS Patients Treated with Azacitidine (AZA): A Prospective Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1917-1917
Author(s):  
Marie Sebert ◽  
Claire Aguilar ◽  
Sylvie Chevret ◽  
Lionel Ades ◽  
Olivier Lortholary ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Fungal Infection ◽  
Predictive Factors ◽  
Invasive Fungal Infection ◽  
Research Funding ◽  
Pulmonary Infection ◽  
Influenza B ◽  
Fatal Infection

Abstract Background: Hypomethylating agents, especially AZA, have become the reference first line treatment of high-risk MDS. Myelosupression, although less important than with chemotherapy, is however observed, leading to potentially life threatening infections. A retrospective study found unfavorable (unfav) cytogenetics and low platelet counts to be predictive factors of infections in high risk MDS and AML patients (pts) receiving AZA (Merkel and al, Am j Hemat 2012). However, prognostic factors of infections, and whether infection prophylaxis would be useful in this situation, has not been prospectively evaluated. Methods: Between June 2011 and March 2013, 120 high-risk MDS pts were included in a randomized phase II trial seeking the most promising drug association with AZA by comparison with AZA alone in higher risk MDS (including AML with 20 to 30% marrow blasts and CMML with > 10% marrow blasts) (NCT01342692). Pts received AZA (75mg/m²/dx7d every 4 weeks) alone (N=40), with Valproic acid (N=40) or with Lenalidomide (N=40) (10mg/dx14d every 4 weeks). G-CSF was not used. Infectious events (IE) (diagnosed as such by the treating physician), hospitalizations for sepsis and pts receiving antimicrobial prophylaxis were reported at each cycle. Predictive factors of the occurrence of IE were analyzed. Results: 75 (62.5%) pts developed 259 IE, including 61 requiring hospitalization in 46 pts (61.3% of infected patients). The number of IE and of infected patients were similar in the 3 study arms. 39 pts died during the study, 12 of them because of infection, none of whom had responded to AZA (4 progressions, 4 failures and 4 deaths before evaluation). IE were more common during the first two cycles of therapy, with 86 (31.3%), 52 (23.5%) 45 (18.9%), 26 (15%), 15(19.2%) and 24 (19.7%) IE during cycles 1, 2, 3, 4, 5, and 6, respectively. Fever of unknown origin (FUO) (39.6%) and pneumonia (28.8%) were the most common type of infections followed by ENT (9.9%), urinary tract (8.1%), skin (5.4%), dental (4.5%) and intra-abdominal (3.6%). 6,3% were bacteriemia. Among the 26 microbiologically documented IE, 13 were CG+ (4 staph aureus, 4 enteroccus species, 4 coag neg staph and 1 other), 9 were BG- (6 E Coli, 1 pseudomonas and 2 others) and 3 were viral (HSV1, influenza B, Hepatitis E) and only one patient had documented invasive fungal infection (asp fumigatus). Overall, 23 (19%), 22 (18%), 10(8%) pts received bacterial (Levofloxacine), fungal (posaconazole) and viral (Valaciclovir) prophylaxis resp. Predictive factors of IE were unfav karyotype (79.5% infections vs. 50.8% in pts with fav or int karyotype; p=0.005) and platelets (PLT) < 20 G/L (92.3% infections vs. 58.9% for platelets > 20 G/L; p=0.03). In multivariate analysis, only unfav karyotype was predictive of IE (p=0.01). Other baseline parameters (including ANC, IPSS, age, sex, Hb level, and BM blast %) and bacterial, fungal or viral prophylaxis had no significant predictive value on the occurrence of IE. In multivariate analysis, predictive factors of pulmonary infection were anemia at baseline (p=0.04) and unfav karyotype (p<0.001), while prophylaxis had no significant impact. Infected pts had significantly more hospitalizations and deaths than non-infected pts (p<0.0001 and p=0.028 resp.). In multivariate analysis, unfav karyotype (p<0.001) and PLT <20 G/L (p=0.05) were significantly predictive of hospitalization for infection, while baseline Hb <10g/dL (p=0.02), and unfav karyotype (p=0.03) were predictors of fatal infection. Conclusion: 62.5% of the 120 pts developed infections during AZA treatment, mainly during the first 2 cycles, and 10% of the pts died from infection. Only one invasive fungal infection was documented. Unfav karyotype was strongly predictive of IE, hospitalization for infection and fatal infections. Other significant predictive factors were baseline anemia for pulmonary infection and fatal infection, and thrombocytopenia for hospitalization for infection, while ANC was not a significant factor. Moreover, prophylaxis was not associated with a decrease of IE in our study, but the small number of pts who received it precludes any conclusion. Disclosures Ades: celgene: Research Funding; Novartis: Research Funding. Fenaux:Novartis: Research Funding; celgene: Research Funding; Janssen: Research Funding.

Induction Therapy with Idarubicin and Etoposide Combined with Sequential or Concurrent Azacitidine In Patients with High-Risk Acute Myeloid Leukemia: Pilot-Phase of the AMLSG 12-09 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2184-2184
Author(s):  
Frank G. Rücker ◽  
Stephan Stilgenbauer ◽  
Martin Bommer ◽  
Daniela Späth ◽  
Silja Mack ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Single Agent ◽  
Severe Toxicity ◽  
Overall Response ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 2184 Background: Treatment outcome in patients with cytogenetically and/or molecularly defined high-risk acute myeloid leukemia (AML) is dismal with low complete remission (CR) rates after intensive induction therapy and 5-year overall survival of about 25% in patients 60 years and younger and far below 5% in patients above the age of 60 years. In younger patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched related or unrelated donors results in significantly better clinical outcome especially if patients are transplanted early in first CR (Schlenk et al., J. Clin. Oncol. 2010, in press). Azacitidine is a demethylating agent showing promising results as a single agent in AML patients with bone marrow blast counts between 20 and 30%. Therefore, the randomized AMLSG 12-09 trial will evaluate the combination of idarubicin/etoposide chemotherapy combined with azacitidine instead of cytarabine as compared to induction with idarubicin/etoposide/cytarabine (ICE) in an attempt to increase CR rates in these high-risk patients. Aim: To evaluate feasibility of the investigational induction therapy with idarubicin and etoposide in combination with sequentially or concurrently administered subcutaneous (sc) azacitidine. Methods: Patients were treated according to the investigational treatment schedules of the AMLSG 12-09 protocol. Patients received idarubicin 12 mg/sqm on days 1, 3 and 5 and etoposide 100 mg/sqm on days 1, 2 and 3 (patients above the age of 65 years received idarubicin 12 mg/sqm and etoposide 100 mg/sqm only on days 1 and 3, respectively). Azacitidine 100 mg/sqm sc was added on days -5 to -1 in 7 patients (schedule A), days 1 to 5 in 6 patients (schedule B), and days 4 to 8 in 5 patients (schedule C). Results: 18 patients have been treated (13 males and 5 females). Median age was 62.5 years (range, 28–76). The cytogenetic and molecular risk profile of the 18 AML was as follows: Eight AML had MDS-related cytogenetic changes (WHO 2008) including five exhibiting a complex karyotype and two had 3q abnormalities; three AML had balanced t(v;11q23), and six exhibited a normal karyotype together with triple negative genotype (NPM1-wt, FLT3-wt and CEBPA-wt). In one case, there were no metaphases available, however molecularly NPM1-wt, FLT3-wt, CEBPA-wt, no core binding factor AML, no t(15;17) and or t(9;11) were present. Median WBC was 4.6/nl (range, 0–6-75/nl). Overall response to induction therapy was CR n=7, partial remission (PR) n=3, refractory disease (RD) n=7 and one patient died during induction therapy (ED). Moreover, two patients with RD achieved CR after additional cycles of single agent azacitidine treatment. Overall response rates (CR and PR) according to treatment schedule were 43% (3/7), 67% (4/6) and 80% (4/5) for schedules A, B and C, respectively. Most common azacitidine-related toxicity was local reactions at injection site not exceeding CTC-grade 2. As expected, fever in neutropenia was the most common severe toxicity (83%). In addition, one patient with history of epilepsy had seizures during induction therapy and one patient with history of Crohn‘s disease had mucositis CTC-grade 3. Allo-HSCT has been performed in three patients and is planned in five. After a median time of 7.5 months, 16 of 18 patients are alive. Conclusion: Azacitidine administered sc can be given safely either sequentially or concurrently in combination with idarubicine/etoposide induction chemotherapy. Response rate of this high-risk population appears promising and the toxicity profile was favorable. The question which schedule is the most effective will be addressed in the randomized AMLSG trial (NCT01180322) Disclosures: Stilgenbauer: Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Döhner: Pfizer: Research Funding. Schlenk: Celgene, Pfizer, Novartis, Cephalon, Amgen: Research Funding.

scholarly journals Genetic Modifiers Identify a High Risk Group for Stroke in Three Independent Cohorts of Sickle Cell Anemia Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1015-1015
Author(s):  
Santosh L. Saraf ◽  
Titilola S. Akingbola ◽  
Binal N. Shah ◽  
Xu Zhang ◽  
Lewis L. Hsu ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell ◽  
Research Funding ◽  
Risk Group ◽  
Linear Trend ◽  
Hemoglobin Concentration ◽  
High Risk Group ◽  
Genetic Modifiers ◽  
History Of ◽  
Hydroxyurea Therapy

Abstract Two common genetic modifiers, α-thalassemia and the BCL11A rs1427407 T allele, are observed in approximately one-third of patients with sickle cell anemia (SCA) and are associated with reduced hemolysis and higher hemoglobin F (HbF) levels, respectively. We investigated the laboratory and clinical effects of α-thalassemia and the BCL11A rs1427407 T allele in the University of Ibadan cohort of SCA patients and replicated our findings in two independent SCA cohorts, University of Illinois at Chicago (UIC) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST). Alpha-thalassemia status was determined by PCR in all 3 cohorts while the BCL11A rs1427407 genotype was determined by PCR in the Ibadan and UIC cohorts and imputed in the Walk-PHaSST cohort. Comparisons according to genotype were performed using the linear trend test for continuous variables and Cochran's test of linear trend for categorical variables. Alpha-thalassemia was observed in 43% of 257 SCA patients from Ibadan and was associated with higher body mass index and lower white blood cell count (Table 1). The BCL11A rs1427407 T allele was observed in 46% of SCA patients from Ibadan and was associated with higher hemoglobin concentration. HbF levels by HPLC were available in 25 patients (12 with the BCL11A rs1427407 T allele) enrolled in a study of low-dose hydroxyurea; these levels were higher in patients with at least one rs1427407 T allele at baseline and progressively during therapy with hydroxyurea 10 mg/kg/day (repeated measures P=0.01). We defined a high risk genetic group as the absence of α-thalassemia in combination with absence of the BCL11A rs1427407 T allele. This high risk group was observed in 31% of SCA patients from the Ibadan cohort and was associated with a higher reticulocyte percentage (15.0% vs. 7.8%, P=0.08) and a higher prevalence for a history of stroke (6% vs. 1%, P=0.02). The association with stroke history persisted on logistic regression analysis after adjusting for age, gender, and hydroxyurea therapy (OR 9.4, 95%CI: 1.2-72.8; P=0.03). We then replicated the association of this high risk group with markers of hemolysis and with history of stroke in the UIC and Walk-PHaSST SCA cohorts. In the UIC cohort, the high risk group was observed in 34% (92/271) and was also associated with higher reticulocyte counts (13.5% vs. 11.9%, P=0.10) and higher prevalence for stroke history (33% vs. 22%; age, gender, HU-adjusted OR 1.7, 95%CI: 1.0-3.0; P=0.066). In the Walk-PHaSST cohort, this high risk profile was observed in 38% (149/394) and was associated with a higher reticulocyte percentage (9.7% vs. 8.4%, P=0.0005), lower hemoglobin concentration (8.4 vs. 8.8 g/dL; P=0.017), and higher prevalence for stroke history (15% vs. 6%; age, gender, HU-adjusted OR 2.6, 95%CI: 1.3-5.3; P=0.007). In conclusion, a high risk group of SCA patients, defined by the lack of the protective α-thalassemia and the BCL11A rs1427407 variants, is associated with a higher degree of hemolysis and a higher prevalence of stroke history on cross sectional analysis in three independent cohorts. This high-risk profile may help identify patients to prioritize for hydroxyurea therapy and for closer monitoring strategies for stroke. Disclosures Hsu: Sancilio: Research Funding; Astra Zeneca: Consultancy, Research Funding; Purdue Pharma: Research Funding; Gerson Lehman Group: Consultancy; Eli Lilly: Research Funding; Centers for Medicare and Medicaid Innovation: Research Funding; Hilton Publishing: Consultancy, Research Funding; Mast Therapeutics: Research Funding; EMMI Solutions: Consultancy; Pfizer: Consultancy, Research Funding.

Donor Type, Chronic Gvhd Subtype , and the Severity of Chronic Gvhd at the Time of Initiation of Chronic Gvhd Treatment Affect Failure-Free Survival in the Patients with Chronic Gvhd

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3139-3139
Author(s):  
Jieun Uhm ◽  
Elizabeth Shin ◽  
Marc Poch Martell ◽  
Fotios V. Michelis ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Overlap Syndrome ◽  
Unrelated Donor ◽  
Free Survival ◽  
Unrelated Donors ◽  
Severe Grade

Abstract Introduction: Chronic graft versus host disease (cGVHD) is one of the major complications after allogeneic hematopoietic cell transplantation (allo-HCT). Several prognostic factors have been proposed to predict the outcomes of cGVHD including progressive type onset, extensive skin involvement, thrombocytopenia and NIH global score (NIH GS). Most studies have been focusing on the factors at the diagnosis of cGVHD without consideration of baseline characteristics prior to allo-HCT. We attempted to evaluate the prognostic factors for the outcomes of cGVHD treatment including the characteristics at the start of cGVHD treatment as well as prior to HCT. Method: We retrospectively reviewed 668 consecutive patients who underwent allo-HCT between 2004 and 2012 at the Princess Margaret Cancer Centre, Toronto, Canada, among whom 277 patients diagnosed as cGVHD and received systemic corticosteroids as a frontline cGVHD therapy. Chronic GVHD was classified and graded using the NIH consensus criteria. We evaluated non-relapse mortality (NRM), relapse and failure-free survival (FFS). FFS was defined as time to a switch in systemic therapy, NRM or relapse. The Kaplan-Meier method was used for FFS. The cumulative incidences of NRM, relapse and the treatment switch (TS) were calculated considering competing risks. Multivariate analysis was performed using the Cox proportional hazard regression model for FFS. Results: With a median follow-up duration of 26 months, the median time from HCT to cGVHD treatment was 183 days (range, 61-828). 102 patients (36.8%) were classified as classical cGVHD and 175 (63.2%) as overlap syndrome. At the start of cGVHD treatment 25 patients (9.0%) had mild cGVHD by the NIH GS, 189 (68.2%) moderate and 63 (22.7%) severe. Median age at allo-HCT was 51 year-old (range, 19-70). 162 patients (58.5%) were males and 65 (23.5%) patients were gender match of female donor to male recipient. 257 patients (92.8%) received peripheral blood stem cells (PBSC).175 grafts (63.2%) were from matched sibling donors (MSD). 180 patients (65%) received myeloablative conditioning. GVHD prophylaxis was calcineurin inhibitor (CNI) and methotrexate (n=82, 29.6%), CNI and mycophenolate mofetil (n=141, 50.9%), CNI and T-cell depletion (n=37, 13.5%) or others (n=17, 6.1%). The median FFS was 255 days (95% CI, 218-321). The severity of cGVHD, NIH GS correlated with FFS: median FFS was 164 days in severe vs 238 days in moderate vs 304 days in mild (p=0.001). The overlap syndrome was associated with a shorter FFS than classical cGVHD (223 vs 329 days, p=0.015). Patients receiving MSD graft showed longer FFS (329 days) than unrelated donor (196 days; p=0.004). The cumulative incidence of TS was 47.7% at 1 year. The NRM was 7.1% and relapse rate was 6.8% at 1 year. The MSD was associated with a lower 1-year NRM than the unrelated donors (4.2% vs 12.3%, p=0.003) while no difference between 2 groups for TS (p=0.731) or relapse at 1 year (p=0.565). Patients with overlap syndrome had higher NRM at 1 year than with classical cGVHD (10.0% vs 2.2%, p=0.009), but no differences in TS or relapse at 1 year (p=0.167 and p=0.138). Chronic GVHD severity by NIH GS showed a significant correlation with TS (28% in mild, 51.9% in moderate, and 43.8% in severe grade at 1 year, p=0.02) and NRM (4% in mild, 3.6% in moderate, and 19.1% in severe grade at 1 year, p<0.001), but with relapse (p=0.784). Multivariate analysis for FFS confirmed that the use of unrelated donor showed a worse FFS (hazard ratio (HR) 1.660, p=0.001). FFS was also associated with the severity of cGVHD, NCC GS (mild vs moderate vs severe; HR 1 vs 2.1 vs 2.9, p=0.002) and the cGVHD subtype (classical vs overlap, HR 1 vs 1.39, p=0.028). We then assigned score 0 for NIH GS mild, 1 for moderate, and 2 for severe; for NIH subtype, score 0 for classical and 1 for overlap; for donor types, score 0 for MSD and 1 for unrelated donors. After summation of the scores, we regrouped them into low (score 0, n=11, 3.9%), intermediate (score 1-2, n=168, 60.6%), and high risk groups (score 3-4, n=98, 35.3%). The risk stratification model correlated nicely with FFS (FFS duration, 1977 days in low vs 341 days in intermediate, and 150 days in high risk group, p<0.001). Conclusion: the use of unrelated donor, overlap subtype of chronic GVHD and severe grade of chronic GVHD at the time of initiation of chronic GVHD treatment affect adversely on failure-free survival. Disclosures Kim: Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

Prognostic Factors of Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Imitanib: A Peruvian Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5444-5444
Author(s):  
José Revilla-López ◽  
Luis Casanova-Márquez ◽  
Cesar Samanez-Figari ◽  
Shirley Quintana-Truyenque ◽  
Kelly Meza-Capcha ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Risk Groups ◽  
Cytogenetic Response ◽  
Prognostic Scores ◽  
Free Survival ◽  
Sokal Score

Abstract Introduction: The introduction of imatinib mesylate as first-line treatment has led to great improvements in the prognosis of patients with chronic myeloid leukemia (CML). The most used prognostic scores are Sokal, EUTOS and Hasford. Also, the time from diagnosis to imatinib and cytogenetic response influence the prognosis of patients with CML. However, there is no information about CML patients in chronic phase treated with imatinib in developing countries. Objectives: The aim of this study was to determine the prognostic factors in Peruvian patients with CML in chronic phase treated with imatinib (Glivec). Methods: Retrospective cohort of peruvian patients with chronic phase CML that received Imatinib (Glivec-Novartis) through the Glivec International Patient Assistance Program (GIPAP) in a national cancer center. The patients were classified according to prognostic scores of Sokal, EUTOS and Hasford at the beginning of imatinib therapy. The overall survival (OS) was calculated from the date of initiation of imatinib until the date of death or last contact. Event-free survival (EFS) was calculated from the date of start of treatment to date of occurrence of death from any cause during treatment, progression to accelerated phase or blast crisis CML or loss of major cytogenetic response. Transformation-free survival (TFS) was calculated from the date of start of treatment to date of occurrence of accelerated progression to blastic phase. Survival curves were estimated by Kaplan-Meier and comparison was done by log-rank test. Multivariate analysis for OS was performed with the Cox proportional hazard regression model. Results: 99 patients met the eligibility criteria and had a median observation time of 71.3 months. The average time from diagnosis to start imatinib was 11.4 months (CI 7.58-15.31). 14% of the patients had an age>55 years. The complete cytogenetic response at 12+3 months was 36%; the partial response was 16.67% and the lower response was 13.89%. According to the criteria of Sokal, EUTOS and Hasford, 59.58%, 49.49% and 27.27% were classified as higher risk, respectively. The 5-yrs-OS was 66.67% (CI 0.04-0.18%); 5-yrs-EFS, 68.63% (CI 0.13-0.38%) and 5-yrs-TFS, 60.82% (CI 0.21-0.41%). The patients with an age>55 years had significantly lower OS compared with the younger patients (p=0.039). The patients with a time higher than 12 months from diagnosis to imatinib had significantly lower OS than the patients that started it earlier (p=0.0076). The OS was significantly different according to the risk groups of Sokal score (p=0.0221). Also, significant difference was found in the EFS according to cytogenetic response (p=0.042). In the multivariate analysis, the factors that influence OS were high risk according toSokal score (HR=9.42 CI1.09-81.29) and a time greater than 12 months from diagnosis Imatinib (HC=3.53 CI1.12-11.18). Conclusion: In this Peruvian population, the majority of patients are at high risk groups of Sokal, EUTOS and Hasford scores. High risk according to Sokal score and a time higher than 12 months from diagnosis to imatinib were the main prognostic factors. Disclosures No relevant conflicts of interest to declare.

Prognostic factors and scoring model for survival in advanced biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 264-264
Author(s):  
Hyung Soon Park ◽  
Ji Soo Park ◽  
Yun Ho Roh ◽  
Jieun Moon ◽  
Dong Sup Yoon ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
High Risk ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Risk Group ◽  
Risk Groups ◽  
Validation Dataset ◽  
Scoring Model ◽  
Tract Cancer

264 Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( < 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P < 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P < 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P< 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection.

scholarly journals Minimal Residual Disease Monitoring By Next-Generation Sequencing in Patients with Acute Myeloid Leukemia: MRD Positivity after First Consolidation Chemotherapy Can Better Predict Clinical Outcomes Than That after Induction Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2698-2698
Author(s):  
Cheng-Hong Tsai ◽  
Jih-Luh Tang ◽  
Feng-Ming Tien ◽  
Yuan-Yeh Kuo ◽  
Chien-Chin Lin ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Research Funding ◽  
Validation Cohort ◽  
Residual Disease ◽  
Risk Group ◽  
Gene Mutations ◽  
Consolidation Chemotherapy ◽  
Generation Sequencing ◽  
Minimal Residual ◽  
Time Point

Introduction Presence of minimal residual disease (MRD) detected by multicolor flow cytometry (MCFC) or quantitative polymerase chain reaction has been recognized as an independent important prognosticator for patients with acute myeloid leukemia (AML). Next-generation sequencing (NGS) can simultaneously detect various mutations and be applied to the majority of patients with AML, but the clinical implication of its use in MRD monitoring remains to be clarified. Recently, it was shown that NGS MRD of mutants other than the common mutations occurring in clonal hematopoiesis of indeterminate potential, including the DTA (DNMT3A, TET2, and ASXL1) mutations, carry prognostic impacts on relapse rates and overall survival (OS) in AML patients. However, the proper time point for NGS MRD detection after treatment is still unclear. Our hypothesis is that the NGS MRD detected at different time points might have different clinical implications. In this regard, we aimed to explore the clinical implication of NGS MRD at different time points in AML patients after chemotherapy. Method We enrolled 306 de novo non-M3 and non-M6 AML patients who attained complete remission (CR) after standard induction chemotherapy and received 2-4 courses of post-remission chemotherapy with high-dose cytarabine with or without anthracycline. We analyzed bone marrow samples serially collected at diagnosis, first CR (1st time point for MRD analysis), and after the first consolidation chemotherapy (2nd time point). We used the TruSight myeloid panel (Illumina) to survey the 54 genes related to myeloid malignancies. Because of the sequencing sensitivity issue, we excluded CEBPA mutation and FLT3-ITD in the subsequent analyses. The median follow-up time was 92.0 months. Result At diagnosis, 91% of patients had at least one gene mutation with a median of 2.0 mutations (range 1-6) per patient; 49.4% had molecular gene mutations alone and 41.6% had both cytogenetic changes and molecular mutations. Mutations in NPM1, DNMT3A, NRAS and IDH2 were the most common mutations. According to the 2017 ELN recommendation, 49.3% of patients were in the favorable-risk group; 29.1%, the intermediate-risk group; and 21.6%, the unfavorable-risk group. Among the patients harboring at least one gene mutation at diagnosis, we randomly assigned them into the training (n=167) and validation cohort (n=111); the two cohorts had similar clinical features, and distribution of cytogenetic and molecular abnormalities. Based on the result from the analysis in the training cohort, we set 0.3% as the cut-off for MRD positivity because patients carried gene mutations lower than this limit had a similar outcome as those without detectable mutations. The allele frequencies of the mutants in MRD ranged from 0.3 to 50.5%. Excluding DTA mutations, 47.3% patients in the training cohort had MRD at 1st time point, and 26.9% at 2nd time point. The patients with positive NGS MRD had significantly higher relapse rate (P=0.042 for 1st MRD and P=0.035 for 2nd MRD), shorter disease-free survival (DFS, P=0.037 for 1st MRD and P=0.007 for 2nd MRD) and OS (P=0.015 for 1st MRD and P<0.001 for 2nd MRD, Figure 1). In multivariate Cox proportional hazards regression model incorporating age, white blood cell counts at diagnosis, transplantation status, 2017 ELN risk-stratification, number of chemotherapy cycles to attain CR, and the MRD status into analyses (Table 1), the 2nd MRD was an independent poor prognostic factor (P=0.040 for DFS and P=0.005 for OS) but not 1st MRD (P=0.113 for DFS and P=0.072 for OS). In the validation cohort, 2nd MRD positivity also predicted poorer OS and DFS (P=0.023 and P<0.001) but not 1st MRD (P=0.996 and P=0.461). A comparison of NGS with MCFC for the detection of MRD in 73 patients showed that MRD by NGS had significant additive prognostic value. Conclusion NGS-based MRD monitoring can be applied to more than 90% of AML patients who have detectable mutations at diagnosis. The presence of NGS MRD after treatment can predict outcome of AML patients, especially after the first consolidation chemotherapy (2nd MRD). Positivity of 2nd MRD is an independent unfavorable prognostic factor for DFS and OS. Further prospective trials are warranted to validate these findings and to clarify the role of pre-emptive treatment. Disclosures Tsai: Celgene: Research Funding; Astellas, BMS, Celgene, Chugai, Johnson & Johnson, Kirin, Novartis, Pfizer, Roche, Takeda: Honoraria. Tien:Novartis: Other: Travel Grant. Hou:Celgene: Research Funding; Abbvie, Astellas, BMS, Celgene, Chugai, Daiichi Sankyo, IQVIA, Johnson & Johnson, Kirin, Merck Sharp & Dohme, Novartis, Pfizer, PharmaEssential, Roche, Takeda: Honoraria. Tien:Celgene: Honoraria; Novartis: Honoraria; Alexion: Honoraria; BMS: Honoraria; Roche: Research Funding; Pfizer: Honoraria; Roche: Honoraria; Celgene: Research Funding; Abbvie: Honoraria; Johnson &Johnson: Honoraria; Daiichi Sankyo: Honoraria.

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