Venetoclax combined with modified intensive chemotherapy in newly diagnosed acute myeloid leukemia: a propensity score-matched analysis

Venetoclax combined with modified intensive chemotherapy in newly diagnosed acute myeloid leukemia: a propensity score-matched analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Venetoclax combined with modified intensive chemotherapy in newly diagnosed acute myeloid leukemia: a propensity score-matched analysis Qiaoyi Zhou, Hong Liu, Lihua Wu, Chunhua Liu, Xiyan Wang, Zhenzhen Wang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8657162/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background There were several explorations to combine venetoclax with standard 3 + 7 regimen or modified intensive chemotherapy. However, few of them included direct comparisons between different regimens. Method The study retrospectively collected the information about newly diagnosed AML patients of which 100 induced by the standard 3 + 7 regimen, 22 by the 3 + 7+ventoclax regimen and 19 by the 2 + 5+ventoclax regimen. We performed propensity score-matched analysis to the 3 + 7+ventoclax group and the historical standard 3 + 7 group to adjust age, Charlson comorbidity index and ELN risk category. Furthermore, we tried to explored the feasibility of the 2 + 5+venetoclax regimen to adapt for the older or patients with more complication by comparing to the 3 + 7+venetoclax group. Result Compared with the standard 3 + 7 therapy, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was higher in the 3 + 7+venetoclax group (90.91% vs 63.33%, p = 0.015) and the event-free survival (EFS) was prolonged (P = 0.0072). Besides, venetoclax induced deeper remission for patients at ELN favorable risk. The superiority causing by 3 + 7+V regimen still existed among patients classified as ELN adverse or intermediate risk group. 36.84% of the 2 + 5+ventoclax group aged 60 years old or older. There was no significant difference in CR/CRi rate, OS or EFS between the 2 + 5+venetoclax group and the 3 + 7+venetoclax group. Conclusion The addition of venetoclax to the standard 3 + 7 induction therapy could notably improve the outcome of untreated AML. And the comparable efficiency with considerable security by administrating 2 + 5+venetoclax regimen, make it possible to substitute for the 3 + 7+V regimen as induction treatment, especially for elder patients. AML Venetoclax chemotherapy older patients Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Highlights Venetoclax could further benefit the untreated AML on the base of chemotherapy and achieved deeper remission even for patients at ELN favorable risk. The addition of venetoclax to the standard 3 + 7 induction therapy could notably improve the outcome of untreated AML. Venetoclax combined with the modified intensive chemotherapy may be an alternative choice as induction treatment. 1. introduction The classic anthracycline and cytarabine regimen, also referred to as the 3 + 7 regimen, has become the first-line induction treatment to de novo acute myeloid leukemia (AML) adults expect for acute promyelocytic leukemia for decades. Approximately 40%-85% patients could achieve complete response (CR) or complete response with incomplete hematologic recovery (CRi). Moreover, most of them relapsed and the prognosis was even worse in the elder patients.[ 1 ]Thus, a regimen with higher and deeper remission is needed to explored. Venetoclax, the B-cell lymphoma-2 inhibitor, has exhibited apparent anti-leukemic effect especially for the high-risk AML and the potential for eliminating leukemic stem cells.[ 2 – 4 ] Besides, preclinical trial supported that venetoclax could synergy with anthracycline and cytarabine to reduce AML cells and overcome resistance.[ 5 ] Thus, several researches have tried to explore the feasibility for combination of venetoclax and the intensive chemotherapy. It has been reported in trials applying venetoclax plus 3 + 7 chemotherapy (3 + 7+V) that the CR/CRi rate was about 90%-91% and the estimated 1-year overall survival (OS) was 97% without treatment-related death.[ 6 , 7 ]Besides, studies recently showed that the usage of modified intensive chemotherapy, by changing “3 + 7” regimen into 2 days of idarubicin 12mg/m 2 and 5 days of cytarabine 100mg/m 2 with 14 days of venetoclax (2 + 5+V), as induction treatment to elder patients, gained favorable results. The overall response rate (ORR) in de novo AML patients could even reach 88%-97% and the median overall survive (OS) is 33.1 months with definitely security.[ 8 , 9 ] Inspired by these, we tried to verified the superiority of the 3 + 7+V regimen and explored the feasibility of the 2 + 5+V regimen as induction therapy to untreated AML patients. Therefore, we performed a propensity score matched (PSM) study to compare the outcomes of 3 + 7+V group with historical 3 + 7 group, following by comparison between 2 + 5+V group and 3 + 7+V group to exploring the possibility of dose reduction of cytotoxic agents. 2. method 2.1 data source and outcomes: The study retrospectively collected the information about patients who were firstly diagnosed as AML in Institute of Hematology & Blood Diseases Hospital with available data. The 2 + 5+V group and the 3 + 7+V group consisted of patients being diagnosed and treated between 2023 and 2025. On the other hand, patients who received the standard 3 + 7 regimen between 2016 and 2024 formed the 3 + 7 group. The eligible criteria included: new diagnosed AML excluding acute promyelocytic leukemia, eligible for intensive chemotherapy and receiving at least one dose of intent treatment. The prognosis category and response criterion were according to 2025 NCCN guidelines.[ 10 ] CR was defined as less than 5% blasts in the bone morrow (BM) with absolute neutrophil count (ANC) > 1×10 9 /L and platelet (PLT) > 100×10 9 /L. CRi meted all criteria for CR except for the recovery of either PLT or ANC to the above criteria. Partial remission (PR) was defined as decrease of at least 50% in the percentage of blasts to 5%-25% in the BM and meeting hematologic criteria for CR. Response for patients failed to meet the criteria of CR, CRi or PR was considered as no response (NR).The overall response rate(ORR) consists of CR, CRi and PR. OS was defined as the time from agents administration to death or censored. And Event-free survival (EFS) was the time from therapy initiation to relapse, death or censored. As for those with NR, an event was considered to occur at day 1 of administration. Adverse events were graduated through the version 5.0 of the Common Terminology Criteria for Adverse Events. 2.2 Procedure: Patients received the 2 + 5+V regimen, including idarubicin 12mg/m 2 /day for 2 days, intravenous infusion cytarabine 100mg/m 2 /days for 5 days and oral venetoclax escalating to 400mg for 7 days. In the 3 + 7+V group, owing to the serious myelosuppression causing by applying venetoclax for 14 days observed in first 3 patients, we adapted the venetoclax administration duration to 7 days. Thus, the majority of patients acquired the 3 + 7+V regimen including daunorubicin 60mg/m 2 /day or idarubicin 12 mg/m 2 /day for 3 days and cytarabine 100mg/m 2 /days for 7 days plus venetoclax escalating to 400mg maintaining for 7 days, expect 3 applying venetoclax for 14 days. The dose of venetoclax was adjusted when confronting the usage of CYP3A4 inhibitors such as posaconazole. Moreover, the standard 3 + 7 group was made up of patients receiving daunorubicin 60mg/m 2 /day or idarubicin 12mg/m 2 /day for 3 days and cytarabine 100mg/m 2 /days for 7 days. The response evaluation was done before the initiation of next course. And the minimal residual disease (MRD) assessment was performed by muti-parameter flow cytometry with the accuracy of 10 − 3 . Majority of consolidation regimen in each group was based on high-dose or intermediate-dose cytarabine and hypomethylating agents were administrated as maintenance treatment. After PSM, only 15 patients (9 in the standard 3 + 7 group and 6 in the 3 + 7+V group) decided to apply allogeneic hematopoietic stem cell transplantation owing to the necessity and the financial reason. 2.3 statistical analysis: Propensity-score matching was used to decrease confounding bias and selection bias, by matching the 3 + 7+V and the standard 3 + 7 cohorts in a 1:4 ratio using nearest-neighbor matching with calipers set to 0.2. The matching was based on a multivariate logistic regression model, which covariates were considered as age, Charlson comorbidity index and ELN risk category. Statistical analysis was evaluated by Fisher’s exact test or ꭓ 2 test for categorical variables and Wilcoxon rank sum test for continuous variables at the p < 0.05 confidence level. The OS and EFS were estimated by the Kaplan-Meier method. Log-rank test and Cox proportional hazard modeling were used for the comparison. All the analysis were completed by R software package (version 4.5.0; R Development Core Team). Figures were painted by R 4.5.0 and GraphPad Prism 9.0.0. 3. result 3.1 the 3 + 7+V group versus the standard 3 + 7 group: As for the standard 3 + 7 group,100 patients were eligible for inclusion with 18 receiving idarubicin and 82 acquiring daunorubicin. We performed PSM for totally 100 patients in the standard 3 + 7 group and 22 patients in the 3 + 7+V group adjusting the age, ELN risk category and the Charlson comorbidity index. After PSM, 40 patients in the standard 3 + 7 group were unmatched (32.79%), leaving 82 patients (67.21%) for the final analysis. The median age was 55 years old and the median BM blast percentage was 69.8% at diagnosis in the 3 + 7 group versus 49.6 years old and 56% in the 3 + 7+V group. Female accounted for 55% and 40.9% respectively in two groups. As for ELN risk classification, 47.6% (3 + 7+V vs the 3 + 7 group:46.7% vs 50%), 28% (3 + 7+V vs the 3 + 7 group:25% vs 22.7%) and 24.4% (3 + 7+V vs the 3 + 7 group:28.3% vs 27.3%) of the patients were stratified as favorable, intermediate and adverse ranks respectively. Among them, 23.2% harbored NRAS/KRAS mutation (3 + 7+V vs the 3 + 7 group:31.8% vs 20%),3.7% harbored tp53 mutation (3 + 7+V vs the 3 + 7 group:0% vs 5%) and 14.6% harbored IDH1/2 aberrance (3 + 7+V vs the 3 + 7 group:27.3% vs 10%). (Table 1 summarized the characteristics of matched patients) Table 1 patients’ demographics and clinical characteristics 3 + 7 (N = 60) 3 + 7+V (N = 22) P Age(years) 0.0749 Median [Min, Max] 55.0 [15.0,63.0] 49.5 [16.0,61.0] Sex 0.322 Female 33 (55%) 9 (40.9%) Male 27 (45%) 13 (59.1%) Charlson comorbidity index 0.688 Median [Min, Max] 3.00 [2.00, 7.00] 3.50 [2.00, 6.00] ELN risk stratification 1 Favorable 28 (46.7%) 11 (50%) Adverse 15 (25%) 5 (22.7%) Intermediate 17 (28.3%) 6 (27.3%) BM blast 0.420 Median [Min, Max] 69.8 [21.5, 96.0] 56.0 [20.5, 94.0] Mutations Others 41 (68.3%) 11 (50%) 0.195 IDH1/2 6 (10%) 6 (27.3%) NRAS/KRAS 12 (20%) 7 (31.8%) tp53 3 (5%) 0 (0%) The CR/CRi rates were higher in the 3 + 7+V group than the standard 3 + 7 group, of 63.33% and 90.91% respectively( p = 0.015), and the ORR was 68.33% and 90.91%( p = 0.0468). 80% achieved MRD negative among patients reaching CR/CRi by engaging the 3 + 7+V group after one cycle of induction compared with 63.2% in the 3 + 7 group( p = 0.241). As for patients with intermediate/adverse ELN risk classification AML, the CR/CRi rates could reach 81.82% in the 3 + 7+V group, compared with 43.75% in the standard 3 + 7 group ( p = 0.0394). The MRD negative rate among patients at favorable risk who reaching CR/CRi was inferior in the 3 + 7 group (3 + 7+V:100% vs 3 + 7:62.5%, p = 0.0331). There wasn’t significant distance in response rates when taking certain mutations or FAB categories into consideration which partly owing to the limited population. (Table 2 and Fig. 1 exhibited the response outcomes among some of the subgroups) Table 2 response outcomes with P < 0.05 highlighted by “*” 3 + 7 (N = 60) 3 + 7+V (N = 22) P response 0.0468* CR 34 (56.7%) 17 (77.3%) CRi 4 (6.7%) 3 (13.6%) PR 3 (5%) 0 (0%) CR/CRi rates in different ELN risk groups Favorable 24(85.7%) 11(100%) 0.309 Intermediate/adverse 14(43.8%) 9(81.8%) 0.0394* CR/CRi rates when considering mutations TP53 1(33.3%) 0(0%) IDH1/2 5(83.3%) 6(100%) 1 NRAS/KRAS 9(75%) 6(85.7%) 1 MRD negative rate for patients reached CR/CRi 24(63.2%) 20(80%) 0.241 Early mortality 30-day mortality 0(0%) 1(4.5%) The median OS wasn’t reached in each of the group. The estimated 1-year OS was 89.84% (95% CI:77.34%-100%) in the 3 + 7+V group and 84.81% (95% CI:75.60%-95.15%) in the 3 + 7 group. And the estimated 1-year EFS was 86.36% (95% CI:73.15%-100%) versus 49.31% (95% CI:38.02%-63.96%) respectively. The 3 + 7+V regimen prolonged the EFS (P = 0.0072), although the OS failed to distinguish significantly between two groups among univariable analysis (P = 0.62). (Fig. 2 demonstrated the survival curve). Among patients classified as adverse or intermediate ELN risk category, the estimated 1-year OS and EFS were 80.81% (95% CI:60.04%-100%) and 72.73% (95% CI:50.64%-100%) in the 3 + 7+V group versus 73.47% (95% CI:58.23%-92.69%) and 34.38% (95% CI:21.30%-55.48%) in the 3 + 7 group. It elaborated that the survival benefits still existed among patients classified as ELN adverse or intermediate risk group (EFS: P = 0.033; OS: P = 0.75). The OS and EFS for patients at favorable risk or with FAB M5 morphology illustrated different tendency between two treatment groups. (Fig. 3 demonstrated the survival curve according to different subgroups). As for the side effects, one death was observed within 30 days in the 3 + 7+V group because of sepsis. Grade ≥ 3 myelosuppression was observed in both the 3 + 7+V and the 3 + 7 groups, including thrombocytopenia (100% vs 100%), neutropenia (100% vs 100%) and anemia (100% vs 96.67%). The median nadir counts of blood cells during treatment were 46 (range:25–66) g/L versus 54 (range:33–81) g/L of hemoglobin ( P < 0.01),0.00 (range:0-0.02) *10 9 /L versus 0.015 (range:0-0.5) *10 9 /Lof ANC ( P < 0.01) and 3 (range:1–9) *10 9 /L versus 5 (range:1–14) *10 9 /L of platelet count ( P = 0.019) in the 3 + 7+V group and the 3 + 7 group respectively. Median duration of ANC < 0.5*10 9 /L was 20 (range:6–29) days in the 3 + 7+V group and 16.5 (range:3–33) days in the standard 3 + 7 group ( P = 0.161). The frequence of febrile neutropenia was 95.45% in the 3 + 7+V group and 95% in the 3 + 7 group. Sepsis was observed in 8 patients in the 3 + 7+V group of which 3 was evidenced by next-generation sequencing and 3 in the 3 + 7 group. The gastrointestinal disorders, notably performed as nausea or vomiting, were the most common nonhematologic adverse events expect for the infection. Reversible liver and kidney toxicity was observed in each of the groups. (Table 3 summarized the major nonhematologic toxicity) Table 3 Major nonhematologic adverse events observed in treatment Nonhematologic adverse events 3 + 7 group (N = 60) 3 + 7+V group (N = 22) All Grades Grades ≥ 3 All Grades Grades ≥ 3 Infection Febrile neutropenia 57 (95%) 57 (95%) 21 (95.45%) 21 (95.45%) Sepsis 3 (5%) 3 (5%) 8 (36.36%) 8 (36.36%) Localized infection 55 (91.67%) 55 (91.67%) 14 (63.64%) 14 (63.64%) Cardiac disorders Heart failure 5 (8.33%) 5 (8.33%) 4 (18.18%) 4 (18.18%) Arrhythmia 1 (1.67%) 0 (0) 1 (4.55%) 0 (0) Gastrointestinal disorders Diarrhea 14 (23.33%) 3 (5%) 8 (36.36%) 1 (4.55%) Nausea/vomiting 29 (48.33%) 0 (0) 7 (31.82%) 0 (0) Gastrointestinal obstruction 3 (5%) 1 (1.67%) 1 (4.55%) 0 (0) Gastrointestinal hemorrhage 9 (15%) 0 (0) 3 (13.64%) 1 (4.55%) Constipation 8 (12.5%) 0 (0) 1 (4.55%) 0 (0) Pancreatitis 0 (0) 0 (0) 2 (9.09%) 1 (4.55%) Abdominal pain 9 (15%) 0 (0) 4 (18.18%) 0 (0) Rash 5 (8.33%) 0 (0) 2 (9.09%) 0 (0) Respiratory failure Hypoxia 1 (1.67%) 1 (1.67%) 2 (9.09%) 2 (9.09%) Bronchopulmonary hemorrhage 3 (5%) 0 (0) 2 (9.09%) 1 (4.55%) Nervous system disorders 2 (5.9%) 1 (2.9%) 0 (0) 0 (0) Headache 3 (5%) 0 (0) 3 (13.64%) 0 (0) Numbness 7 (11.67%) 0 (0) 0 (0) 0 (0) Investigations Aminotransferase increased 14 (23.33%) 2 (3.33%) 8 (36.36%) 2 (9.09%) Blood bilirubin increased 31 (51.67%) 2 (3.33%) 14 (63.64%) 4 (18.18%) Creatinine increased 3 (5%) 0 (0) 1 (4.55%) 0 (0) 3.2 the 2 + 5+V group versus the 3 + 7+V group: Furthermore, we collected several contemporary data from patients receiving 3 + 7 regimen plus venetoclax and compared them with the 2 + 5+V group to try to explore the feasibility of the dose reduction of cytotoxic agents without impairing the efficiency. Patients enrolled in the 2 + 5+V group was elder with the median age of 56 years old compared with 49.5 years old in the 3 + 7+V group (P = 0.0185). There were 8 females (42.1%) in the 2 + 5+V group compared with 9 (40.9%) in the 3 + 7+V group.73.7% patients were stratified as ELN intermediate/adverse risk in the 2 + 5+V group versus 50% in the 3 + 7+V group(P = 0.199). (Table 4 demonstrated the baseline information of two groups) Table 4 baseline characters of 3 + 7+V group and 2 + 5+V group with P < 0.05 highlighted by “*” 3 + 7+V (N = 22) 2 + 5+V (N = 19) P value Age(years) 0.0185* Median [Min, Max] 49.5 [16.0, 61.0] 56 [24.0, 73.0] sex 1 Female 9 (40.9%) 8 (42.1%) Male 13 (59.1%) 11 (57.9%) Charlson comorbidity index 0.325 Median [Min, Max] 3.50 [2.00, 6.00] 3.00 [2.00, 7.00] ELN risk category 0.398 Favorable 11 (50.0%) 5 (26.3%) Adverse 5 (22.7%) 6 (31.6%) Intermediate 6 (27.3%) 8 (42.1%) BM blast percentage (%) 0.666 Median [Min, Max] 56.0 [20.5, 94.0] 59.0 [4.50, 95.0] Mutations Others 11 (50.0%) 14 (73.7%) 0.199 IDH1/2 6 (27.3%) 3 (15.8%) NRAS/KRAS 7 (31.8%) 3 (15.8%) tp53 0 (0%) 0 (0%) The CR/CRi rate was 84.21% in patients receiving the 2 + 5+V regimen and 90.91% in patients receiving 3 + 7+V (OR:0.990, P = 0.993). And the MRD negative rate among patients reaching CR/CRi was 93.75% in the 2 + 5+V group versus 80% in the 3 + 7+V group(P = 0.355). Among patients classified as ELN intermediate or adverse risk, the CR/CRi rates achieved 85.71% and 81.82% respectively. In the ELN favorable risk group, all patients reaching CR/CRi achieved MRD negative, regardless of the regimen selection. (Fig. 4 exhibited the odds ratios of failure to CR/CRi) With a median follow-up duration of 274 days, the median OS and EFS were no reached in each of the groups. The 1-year estimated OS and EFS were 87.45% (95%CI:72.36%-100%) and 77.20% (95%CI:59.60%-100%) respectively in the 2 + 5+V group versus 89.84% (95%CI:77.34%-100%) and 86.36% (73.15%-100%) in the 3 + 7+V group. The OS (P = 0.81) and the EFS (P = 0.31) weren’t significantly distinct between two groups under univariate analysis. (Fig. 5 showed the survival curve between two groups) The selection of regimen still failed to differ the OS (HR:0.398, P = 0.457) and the EFS (HR:0.695, P = 0.677) when considered age and ELN risk rank as confounding factors. (Fig. 6 showed the hazard ratio of age, ELN risk rank and the regimen for OS and EFS) All patients suffered from grade ≥ 3 myelosuppression in the 2 + 5+V group and the 3 + 7+V group, including thrombocytopenia (100% vs 100%), neutropenia (100% vs 100%) and anemia (94.74% vs 100%).The median duration of ANC < 0.5*10 9 /L was 17 days (range:5–25 days) in the 2 + 5+V group and 20 days (range:6–29 days) in the 3 + 7+V group respectively (P = 0.113).The frequence of febrile neutropenia was 84.21% in the 2 + 5+V group and 95.45% in the 3 + 7+V group(P = 0.321). One patient from each group died within 30 days because of sepsis. 31.58% patients were considered to experience sepsis in the 2 + 5+V groups compared with 36.36% in the 3 + 7+V group. Expect for the infection, the gastrointestinal disorders were the most common nonhematologic adverse events. None of the patients in 2 + 5+V group suffered grade ≥ 3 gastrointestinal disorder compared with 3 in the 3 + 7+V group. Besides, liver and kidney toxicity appeared more serious in the latter group. Grade ≥ 3 heart failure was detected in 4 cases in each of the group. (Table 5 summarized the major nonhematologic toxicity) Table 5 the nonhematologic toxicity between two groups Nonhematologic adverse events 3 + 7+V group (N = 22) 2 + 5+V group (N = 19) All Grades Grades ≥ 3 All Grades Grades ≥ 3 Infection Sepsis 8 (36.36%) 8 (36.36%) 6 (31.58%) 6 (31.58%) Localized infection 14 (63.64%) 14 (63.64%) 12 (63.16%) 10 (52.63%) Cardiac disorders Heart failure 4 (18.18%) 4 (18.18%) 5 (26.32%) 4 (21.05%) Arrhythmia 1 (4.55%) 1 (4.55%) 1 (5.26%) 1 (5.26%) Gastrointestinal disorders Diarrhea 8 (36.36%) 1 (4.55%) 2 (10.53%) 0 (0) Nausea/vomiting 7 (31.82%) 0 (0) 6 (31.58%) 0 (0) Gastrointestinal obstruction 1 (4.55%) 0 (0) 2 (10.53%) 0 (0) Gastrointestinal hemorrhage 3 (13.64%) 1 (4.55%) 0 (0) 0 (0) Constipation 1 (4.55%) 0 (0) 2 (10.53%) 0 (0) Pancreatitis 2 (9.09%) 1 (4.55%) 0 (0) 0 (0) Rectal perforation 0 (0) 0 (0) 2 (10.53%) 0 (0) Rash 2 (9.09%) 0 (0) 2 (10.53%) 0 (0) Respiratory failure 2 (9.09%) 2 (9.09%) 1 (5.26%) 1 (5.26%) Headache 3 (13.64%) 0 (0) 0 (0) 0 (0) Investigations Aminotransferase increased 8 (36.36%) 2 (9.09%) 4 (21.05%) 0 (0) Blood bilirubin increased 14 (63.64%) 4 (18.18%) 10 (52.63%) 2 (10.53%) Creatinine increased 1 (4.55%) 0 (0) 0 (0) 0 (0) Cardiac troponin I increased 1 (4.55%) 0 (0) 0 (0) 0 (0) 3.3 supplement: We suppled three additional cases in which the 2 + 5+V regimen was administrated as reinduction therapy when the disease relapsed for the first time. All of them achieved CR/CRi again after receiving the 2 + 5+V reinduction and two of them even reached MRD negative, indicated that the regimen may come across part of the resistance mechanism and be efficient to relapsed leukemia. (Fig. 7 demonstrated the response and long-term survival of these three patients and the other 19 cases of new diagnosed AML as mentioned before in the 2 + 5+V group) 4. discussion Compared with the standard 3 + 7 group, the CR/CRi rates were higher in the 3 + 7+V group (90.91% vs 63.33%, P = 0.015) with 80% undetectable MRD in all of these responded cases, indicating that the 3 + 7+V regimen can bring more considerable and deeper remission to patients with new diagnosed AML. Besides, the 3 + 7+V regimen, by engaging which the estimated 1-year OS and EFS could reach 89.84% and 86.36% respectively, appeared favor to prolonged EFS (P = 0.0072). The superiority causing by 3 + 7+V regimen still existed among patients classified as ELN adverse or intermediate risk group. Both the hematologic toxicity and the nonhematologic adverse events of the 3 + 7+V regimen showed more severe though the duration of neutrophile granulocyte recovery wasn’t extremely expended. One patient died for sepsis within 30 days after therapy administration in the 3 + 7+V group and no early mortality was observed in the standard 3 + 7 group. 8 patients developed sepsis by using the 3 + 7+V regimen, compared with 3 in the 3 + 7 group. Gastrointestinal disorders were the most common nonhematologic side effect in each of the groups in line with previous researches. The liver and kidney toxicity were reversible in both groups. Furthermore, we tried to explore the feasibility of engaging 2 + 5+V regimen for reducing the adverse events without impairing efficiency. The median age of the 2 + 5+V group was 56 (range:24–73) years old with 36.84% aged 60 years old or older compared with 49.5 years old (range:16–61) years old ( P = 0.0185) with only 4.45% aged 60 years old or older in the 3 + 7+V group. Besides, 73.7% patients were stratified as ELN intermediate/adverse risk in the 2 + 5+V group versus 50% in the 3 + 7+V group(P = 0.199). The CR/CRi rates showed no significantly difference between two groups (90.91% vs 84.21%, OR:0.990, P = 0.993). Besides, 93.75% among the responded patients achieved MRD negative in the 2 + 5+V group compared with 80% in the 3 + 7+V group (P = 0.355). In the former group, the 1-year estimated OS and EFS were 87.45% (95%CI:72.36%-100%) and 77.20% (95%CI:59.60%-100%) respectively. The alternation of regimen failed to demonstrate survival benefit in both univariate and multivariate analysis. Compared with the 3 + 7+V group, the median duration of neutropenia (17 days vs 20 days) and the frequence of febrile neutropenia (84.21% vs 95.45%) were lower in the 2 + 5+V group and the nonhematologic toxicity was slighter. The gastrointestinal disorders were better tolerated in the latter group. Thus, the dose reduction of cytotoxic agents was feasible, especially for patients with heart diseases considering the cardiac toxicity caused by anthracycline cumulated. Inspired by the less toxicity and considerable efficiency in treating ineligible patients with untreated AML, [ 2 ] venetoclax added to hypomethylating agents (HMA) started to be used as induction regimen to fit AML patients. The reported CR/CRi rate was approximate 81%-89%, superiority to the traditional 3 + 7 regimen,[ 11 – 13 ] similar with the response rates on the 3 + 7+V or 2 + 5+V regimen. Besides, previous researches reported that the 3 + 7 regimen favored to patients at favorable/intermediate risk or with FAB M5 morphology relative to venetoclax plus HMA.[ 11 , 13 – 19 ]In our analysis, venetoclax induced deeper remission in patients at favorable risk and demonstrated numerically incremental benefits of the CR/CRi rates and survival prolongation to both favorable risk and FAB M5 AML. And the optimum wasn’t impaired by the reduction of cytotoxic agents. Moreover, we supplied three relapsed AML cases and all of them reached CR/CRi by administrating the 2 + 5+V regimen as reinduction therapy, implying the potential of the regimen to eliminate the resistant leukemic cells. There were still lots of limitation in the study. Due to the small population, we failed to analyze the outcome between patients harboring different mutations, such as IDH2 , which was demonstrated to be benefit from venetoclax previously. [ 20 – 23 ] And the response rates were analyzed only after receiving one course of induction. Besides, the bias and the detriment to generalizability were inevitable for the single-center retrospective study. Therefore, larger, muti-center and prospective studies will be required. Overall, the addition of venetoclax to the standard 3 + 7 induction therapy could notably improve the outcome of newly diagnosed AML patients. And the comparable efficiency with considerable security by administrating 2 + 5+V regimen, consisting of idarubicin for 2 days, cytarabine for 5 days and venetoclax for 7 days, make it possible to substitute for the 3 + 7+V regimen as induction treatment, especially for elder patients. Abbreviations AML Acute myeloid leukemia ANC Absolute neutrophil count BM Bone morrow CR Complete remission CRi Complete remission with incomplete hematologic recovery EFS Event-free survival ELN European Leukemia Net HR Hazard ratio NCCN National Comprehensive Cancer Network NR No response MRD minimal residual disease OR Odds ratio ORR Overall response rate OS Overall survival PLT Platelet PR Partial remission PSM Propensity score matched Declarations Ethics approval and consent to participate: This research study was approved by the Ethics Committees of the Institute of Hematology & Blood Diseases Hospital (approval number: IIT2021028-EC-1) and informed consent was obtained from all patients. All procedures adhered to the principles outlined in the Declaration of Helsinki. None of the patients’ name or other personal information was disclosed. Consent for publication: Not applicable. Data availability: The data that support the findings of this study are available from the corresponding author (Ying Wang) upon reasonable request. Competing interests: The authors declared no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding: This study was supported by Tianjin Key Medical Discipline Construction Project under Grant TJYXZDXK-3-001A. Author Contributions: Conceptualization, methodology and funding acquisition: Ying Wang. Supervision: Shuning Wei. Writing-original draft preparation, writing-review and editing and formal analysis: Qiaoyi Zhou. Investigation: Hong Liu. Project administration: Hong Liu, Lihua Wu，Chunhua Liu，Xiyan Wang，Zhenzhen Wang，Lijun Fang, Runxia Gu, Shuning Wei. Acknowledgements: We thank the patients and the staff. References Döhner H, Bloomfield WD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep;17(12):1152. DiNardo CD, Pullarkat JB, Thirman V, Garcia MJ, Wei JS, Konopleva AH, Döhner M, Letai H, Fenaux A, Koller P, Havelange E, Leber V, Esteve B, Wang J, Pejsa J, Hájek V, Porkka R, Illés K, Lavie Á, Lemoli D, Yamamoto RM, Yoon K, Jang SS, Yeh JH, Turgut SP, Hong M, Zhou WJ, Potluri Y. Pratz KW., Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia . N Engl J Med. 2020 Aug;13(7):629. Ohmoto A. F.S., Clinical status of induction therapy incorporating a hypomethylating agent for newly diagnosed adult acute myeloid leukemia compared to the standard 7 + 3 regimen. Expert Rev Hematol 2023 Jul-Dec. 16(10): p. 771. Lagadinou ED, Callahan SA, Rossi K, Neering RM, Minhajuddin SJ, Ashton M, Pei JM, Grose S, O'Dwyer V, Liesveld KM, Brookes JL, Becker PS, Jordan MW. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013 Mar;7(3):341. Teh TC, Moujalled NN, Segal DM, Pomilio D, Rijal G, Jabbour S, Cummins A, Lackovic K, Blombery K, Thompson P, Ekert E, Lessene PG, Glaser G, Huang SP, Roberts DCS, Guthridge AW, Wei MA. AH., Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1. Leukemia., 2018 Feb. 32(2). Wang R, Chang ZY, Wang J, Lou H, Yang Y, Xu M, Tong G, Xie H, Zhou W, Wei D, Mai J, Ye W, Meng X, Jin H, Zhu J. HH, Venetoclax plus daunorubicin and cytarabine in newly diagnosed acute myeloid leukemia patients: A propensity score-matched analysis. Hematol Oncol., 2024 Mar. 42(2). Wang H, Yang ML, Qian M, Lu P, Tong H, Xie H, Zhou W, Huang D, Wang X, Xu Y, Lu G, Wei Y, Mai J, Ye W, Meng X, Shen H, Huang Y, Yu J, Sun W, Sheng J, Yan J, Jin X, Zhu J. Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2022 Jun;9(6):e424. Chua CC, Fong LS, Ting CY, Tiong SB, Fleming IS, Anstee SA, Ivey NS, Ashby A, Teh M, Reynolds TC, Roberts J, Wei AW. AH., Final Analysis of the Phase 1b Chemotherapy And Venetoclax in Elderly Acute Myeloid Leukaemia Trial (CAVEAT). Blood Adv., 2025 Jan 18. bloodadvances.2024014900. Chua CC, Reynolds RA, Fong J, Ting CY, Salmon SB, MacRaild JM, Ivey S, Tiong A, Fleming IS, Brown S, Loo FC, Majewski S, Bohlander IJ, Wei SK. Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy. J Clin Oncol. 2020 Oct;20(30):3517. Network NCC. Acute Myeloid Leukemia(Version 2.2025) . 2025 [cited 2025 August 6]; Available from: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf Lu J, Wang XS, He Y, Hu XF, Miao XH, Zhang M, Tang Y, Xie ZX, Yang JD, Xu XF, Shen MZ, Du YY, Wu F, Xue Q, Wang MX, Deng Y, Dou AL, Xu XQ, Dai Y, Wu HP, Chen DP. Venetoclax and decitabine vs intensive chemotherapy as induction for young patients with newly diagnosed AML. Blood. 2025 May;29(22):2655. Amir Fathi AP, Fell G, Jonas B, Ragon B, Mims A, Borate U, Mannis G, Quillen K, Stahl M, Koller P, Artz A, Malki MMA, Marcucci G, Peters ML, Graubert T, Westervelt P, Philip Amrein, Hanno Hock, Andrew Brunner, Gabriela Hobbs, Rupa Narayan, Michelle Lee, Brandon Aubrey, Watson A, Hao R, Dhaver S, Grunwald M, Chen Y-B. Andrew Matthews, Christopher Hourigan, Brent Wood, Donna Neuberg, Areej El-Jawahri, Ibrahim Aldoss, Results from paradigm - a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia. Blood., 2025. 146(Supplement 1). Xu X, Chen LR, Yang H, Gao R, He G, Wang A. Single-center experience of venetoclax combined with azacitidine in young patients with newly diagnosed acute myeloid leukemia. Ther Adv Hematol. 2025 Jan;6:16. Cherry EM, Amaya AD, McMahon M, Schwartz C, Rosser M, Sato J, Schowinsky A, Inguva J, Minhajuddin A, Pei M, Stevens S, Winters B, Jordan A, Smith CT, Gutman C, Pollyea JA. Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia. Blood Adv. 2021 Dec;28(24):5573. Zeidan AM, Borate PD, Vasconcelos U, Potluri A, Rotter R, Kiendrebeogo D, Gaugler Z, Prebet L, Strocchia T, Bonifacio M, Chen G. C., Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States. Ann Hematol., 2023 Apr. 102(4): p. 754. Ravindran M, Cheung ML, Buckstein M, Teichman R. A Markov analysis of azacitidine and venetoclax vs induction chemotherapy for medically fit patients with AML. Blood Adv. 2024 Feb;13(3):639. Zhang K, Xu ZX, Xue Y, Qiu S, Tang H, Han X, Chen Y, Sun S, Zhang A, Wu Y, Wang D. Y, Efficacy of venetoclax combined with hypomethylating agents in young, and unfit patients with newly diagnosed core binding factor acute myeloid leukemia. Blood Cancer J, 2023 Oct 11. 13(1). Wang M, Tan CH, Qiu KW, Huang QC, Ge YH, Wang SS, Chen ZH, Tang J, Wu XW, Xue DP, Li SL, Dai Z. HP, Venetoclax plus hypomethylating agents in newly diagnosed acute myeloid leukemia patients with RUNX1::RUNX1T1: a retrospective propensity score matching study. Blood Cancer J 2023 Nov 27. 13(1). Jin D, He CH, Li J, Zheng Y, Yang G, Zhao Y, Le Y, Shu J, He W, Cai D. Z, Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia. Target Oncol., 2024 Mar. 19(2): p. 249. Döhner H, Appelbaum DC, Craddock FR, Dombret C, Ebert H, Fenaux BL, Godley P, Hasserjian LA, Larson RP, Levine RA, Miyazaki RL, Niederwieser Y, Ossenkoppele D, Röllig G, Sierra C, Stein J, Tallman EM, Tien MS, Wang HF, Wierzbowska J, Wei A, Löwenberg AH. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood. 2024 Nov;21(21):2173. Qin Y, Liu KP. Venetoclax combined with hypomethylating agents or low-dose cytarabine as induction chemotherapy for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: a systematic review and meta-analysis. Clin Exp Med. 2023 Jun;23(2):227. Short NJ, Qiao VS, Kadia W, Ravandi TM, Macaron F, Dinardo W, Daver CD, Konopleva N, Borthakur M, Shpall G, Popat EJ, Champlin U, Mehta RE, Al-Atrash R, Oran G, Jabbour B, Garcia-Manero E, Issa G, Montalban-Bravo GC, Yilmaz G, Maiti M, Kantarjian A. H, Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure. J Hematol Oncol, 2022 Jan 29. 15(1). DiNardo CD, Quaglieri TI, MacRaild A, Loghavi S, Brown S, Thijssen FC, Pomilio R, Ivey G, Salmon A, Glytsou JM, Fleming C, Zhang SA, Ma Q, Patel H, Kornblau KP, Xu SM, Chua Z, Chen CC, Blombery X, Flensburg P, Cummings C, Aifantis N, Kantarjian I, Huang H, Roberts DCS, Majewski AW, Konopleva IJ, Wei M. Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood. 2020 Mar;12(11):803. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8657162","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":593251723,"identity":"6fa73f1b-56fa-43d1-ae9d-cd9f910ae94f","order_by":0,"name":"Qiaoyi Zhou","email":"","orcid":"","institution":"State Key Laboratory of Experimental Hematology","correspondingAuthor":false,"prefix":"","firstName":"Qiaoyi","middleName":"","lastName":"Zhou","suffix":""},{"id":593251724,"identity":"e708000b-250f-4c7c-a5c8-932b32928f01","order_by":1,"name":"Hong Liu","email":"","orcid":"","institution":"State Key Laboratory of Experimental Hematology","correspondingAuthor":false,"prefix":"","firstName":"Hong","middleName":"","lastName":"Liu","suffix":""},{"id":593251725,"identity":"3c6f67f4-547f-4372-b721-4c0a38521a61","order_by":2,"name":"Lihua Wu","email":"","orcid":"","institution":"State Key Laboratory of Experimental Hematology","correspondingAuthor":false,"prefix":"","firstName":"Lihua","middleName":"","lastName":"Wu","suffix":""},{"id":593251726,"identity":"506ab4a5-e885-4c24-911b-08bc5390cfad","order_by":3,"name":"Chunhua Liu","email":"","orcid":"","institution":"State Key Laboratory of Experimental Hematology","correspondingAuthor":false,"prefix":"","firstName":"Chunhua","middleName":"","lastName":"Liu","suffix":""},{"id":593251727,"identity":"c3c94f24-be3c-45f9-a288-9805abbdd21f","order_by":4,"name":"Xiyan Wang","email":"","orcid":"","institution":"State Key Laboratory of Experimental 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Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYNACAwYGNvbGNhK18PEcJEkLEMhJJLARaf7xs4df8xTcsWuTfNz24EfNNnsG9sMPGH7uwKPlTF6aNY/Bs+Q26cR2w55jtxMbeNIMGHvP4NZidiDHzJjH4HAym3RimzQD2+0EBoYcBmZGPP4yO/8GqkXyIFDLv9v2DPxvCGi5kWP8GKjFjk2CsU2ase02Y4MEAVvsb7wxY5xjcDiBjSexTbK373Zim8Qzg4O9eLRI9ucYf3jz57C9fPvxZxI/vt225+dPfvjgJ/44YpPiYWBIbIBzgfgAXg0MDMwffwAdSEDRKBgFo2AUjGQAAKQuT8bDtiv0AAAAAElFTkSuQmCC","orcid":"","institution":"State Key Laboratory of Experimental Hematology","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-01-21 08:34:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8657162/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8657162/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505682,"identity":"fdecbd23-24f4-4707-98a2-b64119a58bf7","added_by":"auto","created_at":"2026-02-26 13:32:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":228863,"visible":true,"origin":"","legend":"\u003cp\u003eThe ORR, CR/CRi rates and the MRD negative rates among patients at favorable risk or with FAB M5 morphology.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/a9063429d217667f82da7f99.png"},{"id":103167944,"identity":"3e29e873-b547-46be-9629-b8248fdf45d8","added_by":"auto","created_at":"2026-02-22 12:56:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151362,"visible":true,"origin":"","legend":"\u003cp\u003eThe OS curve and the EFS curve between two groups\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/209590ffb19a7d645476b8c3.png"},{"id":103167943,"identity":"3765fa0f-69c0-4d60-bcfd-382eacfea54d","added_by":"auto","created_at":"2026-02-22 12:56:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":426479,"visible":true,"origin":"","legend":"\u003cp\u003eThe OS curve and the EFS curve among patients classified as ELN favorable group(a), ELN adverse or intermediate risk group(b) or with FAB M5 morphology(c).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/2abe70adcf9ab397b31e58a3.png"},{"id":103505293,"identity":"10a765d0-c1be-4996-ae58-1c5e46a799b1","added_by":"auto","created_at":"2026-02-26 13:29:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":106236,"visible":true,"origin":"","legend":"\u003cp\u003eThe odds ratios of failure to CR/CRi when considering age, ELN risk category and the regimen. OR\u0026lt;1 demonstrated that the factor was in favor of reaching CR/CRi.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/b1fb1972fd4a01ed46188a8d.png"},{"id":103167947,"identity":"2302b439-72bf-4e00-aa45-ca7c576122c4","added_by":"auto","created_at":"2026-02-22 12:56:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":134713,"visible":true,"origin":"","legend":"\u003cp\u003ethe OS and the EFS between two groups\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/ae0a86d860491b91c6b85b26.png"},{"id":103167948,"identity":"6934bf28-fc0b-4327-8c4a-0ed4fdcfd786","added_by":"auto","created_at":"2026-02-22 12:56:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":173329,"visible":true,"origin":"","legend":"\u003cp\u003ethe hazard ratio of age, ELN risk rank and the regimen for OS and EFS. Variant with HR\u0026lt;1was explained as a protective factor beneficial for longer survival.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/bcc4e22b29abf2b2c529c96d.png"},{"id":103504862,"identity":"3a6a9c35-6186-45f2-8c12-049839f619b8","added_by":"auto","created_at":"2026-02-26 13:21:49","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":177891,"visible":true,"origin":"","legend":"\u003cp\u003eResponse and long-term survival of 22 cases receiving the 2+5+V regimen\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/e32e73b0adb5b527fa9c94f5.png"},{"id":109204898,"identity":"e82fdaae-7959-4ea5-a9ad-f548c6dc6a27","added_by":"auto","created_at":"2026-05-13 15:02:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1813925,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8657162/v1/d5efcdf3-5765-4820-b11a-ee6a1d135938.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Venetoclax combined with modified intensive chemotherapy in newly diagnosed acute myeloid leukemia: a propensity score-matched analysis","fulltext":[{"header":"Highlights","content":"\u003cp\u003eVenetoclax could further benefit the untreated AML on the base of chemotherapy and achieved deeper remission even for patients at ELN favorable risk.\u003c/p\u003e\u003cp\u003eThe addition of venetoclax to the standard 3\u0026thinsp;+\u0026thinsp;7 induction therapy could notably improve the outcome of untreated AML.\u003c/p\u003e\u003cp\u003eVenetoclax combined with the modified intensive chemotherapy may be an alternative choice as induction treatment.\u003c/p\u003e"},{"header":"1. introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe classic anthracycline and cytarabine regimen, also referred to as the 3\u0026thinsp;+\u0026thinsp;7 regimen, has become the first-line induction treatment to de novo acute myeloid leukemia (AML) adults expect for acute promyelocytic leukemia for decades. Approximately 40%-85% patients could achieve complete response (CR) or complete response with incomplete hematologic recovery (CRi). Moreover, most of them relapsed and the prognosis was even worse in the elder patients.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]Thus, a regimen with higher and deeper remission is needed to explored.\u003c/p\u003e \u003cp\u003eVenetoclax, the B-cell lymphoma-2 inhibitor, has exhibited apparent anti-leukemic effect especially for the high-risk AML and the potential for eliminating leukemic stem cells.[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Besides, preclinical trial supported that venetoclax could synergy with anthracycline and cytarabine to reduce AML cells and overcome resistance.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Thus, several researches have tried to explore the feasibility for combination of venetoclax and the intensive chemotherapy. It has been reported in trials applying venetoclax plus 3\u0026thinsp;+\u0026thinsp;7 chemotherapy (3\u0026thinsp;+\u0026thinsp;7+V) that the CR/CRi rate was about 90%-91% and the estimated 1-year overall survival (OS) was 97% without treatment-related death.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]Besides, studies recently showed that the usage of modified intensive chemotherapy, by changing \u0026ldquo;3\u0026thinsp;+\u0026thinsp;7\u0026rdquo; regimen into 2 days of idarubicin 12mg/m\u003csup\u003e2\u003c/sup\u003e and 5 days of cytarabine 100mg/m\u003csup\u003e2\u003c/sup\u003e with 14 days of venetoclax (2\u0026thinsp;+\u0026thinsp;5+V), as induction treatment to elder patients, gained favorable results. The overall response rate (ORR) in de novo AML patients could even reach 88%-97% and the median overall survive (OS) is 33.1 months with definitely security.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eInspired by these, we tried to verified the superiority of the 3\u0026thinsp;+\u0026thinsp;7+V regimen and explored the feasibility of the 2\u0026thinsp;+\u0026thinsp;5+V regimen as induction therapy to untreated AML patients. Therefore, we performed a propensity score matched (PSM) study to compare the outcomes of 3\u0026thinsp;+\u0026thinsp;7+V group with historical 3\u0026thinsp;+\u0026thinsp;7 group, following by comparison between 2\u0026thinsp;+\u0026thinsp;5+V group and 3\u0026thinsp;+\u0026thinsp;7+V group to exploring the possibility of dose reduction of cytotoxic agents.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"2. method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 data source and outcomes:\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe study retrospectively collected the information about patients who were firstly diagnosed as AML in Institute of Hematology \u0026amp; Blood Diseases Hospital with available data. The 2\u0026thinsp;+\u0026thinsp;5+V group and the 3\u0026thinsp;+\u0026thinsp;7+V group consisted of patients being diagnosed and treated between 2023 and 2025. On the other hand, patients who received the standard 3\u0026thinsp;+\u0026thinsp;7 regimen between 2016 and 2024 formed the 3\u0026thinsp;+\u0026thinsp;7 group. The eligible criteria included: new diagnosed AML excluding acute promyelocytic leukemia, eligible for intensive chemotherapy and receiving at least one dose of intent treatment.\u003c/p\u003e\u003cp\u003e The prognosis category and response criterion were according to 2025 NCCN guidelines.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] CR was defined as less than 5% blasts in the bone morrow (BM) with absolute neutrophil count (ANC)\u0026thinsp;\u0026gt;\u0026thinsp;1\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L and platelet (PLT)\u0026thinsp;\u0026gt;\u0026thinsp;100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L. CRi meted all criteria for CR except for the recovery of either PLT or ANC to the above criteria. Partial remission (PR) was defined as decrease of at least 50% in the percentage of blasts to 5%-25% in the BM and meeting hematologic criteria for CR. Response for patients failed to meet the criteria of CR, CRi or PR was considered as no response (NR).The overall response rate(ORR) consists of CR, CRi and PR. OS was defined as the time from agents administration to death or censored. And Event-free survival (EFS) was the time from therapy initiation to relapse, death or censored. As for those with NR, an event was considered to occur at day 1 of administration. Adverse events were graduated through the version 5.0 of the Common Terminology Criteria for Adverse Events.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Procedure:\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePatients received the 2\u0026thinsp;+\u0026thinsp;5+V regimen, including idarubicin 12mg/m\u003csup\u003e2\u003c/sup\u003e/day for 2 days, intravenous infusion cytarabine 100mg/m\u003csup\u003e2\u003c/sup\u003e/days for 5 days and oral venetoclax escalating to 400mg for 7 days. In the 3\u0026thinsp;+\u0026thinsp;7+V group, owing to the serious myelosuppression causing by applying venetoclax for 14 days observed in first 3 patients, we adapted the venetoclax administration duration to 7 days. Thus, the majority of patients acquired the 3\u0026thinsp;+\u0026thinsp;7+V regimen including daunorubicin 60mg/m\u003csup\u003e2\u003c/sup\u003e/day or idarubicin 12 mg/m\u003csup\u003e2\u003c/sup\u003e/day for 3 days and cytarabine 100mg/m\u003csup\u003e2\u003c/sup\u003e/days for 7 days plus venetoclax escalating to 400mg maintaining for 7 days, expect 3 applying venetoclax for 14 days. The dose of venetoclax was adjusted when confronting the usage of CYP3A4 inhibitors such as posaconazole. Moreover, the standard 3\u0026thinsp;+\u0026thinsp;7 group was made up of patients receiving daunorubicin 60mg/m\u003csup\u003e2\u003c/sup\u003e/day or idarubicin 12mg/m\u003csup\u003e2\u003c/sup\u003e/day for 3 days and cytarabine 100mg/m\u003csup\u003e2\u003c/sup\u003e/days for 7 days.\u003c/p\u003e \u003cp\u003eThe response evaluation was done before the initiation of next course. And the minimal residual disease (MRD) assessment was performed by muti-parameter flow cytometry with the accuracy of 10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e. Majority of consolidation regimen in each group was based on high-dose or intermediate-dose cytarabine and hypomethylating agents were administrated as maintenance treatment. After PSM, only 15 patients (9 in the standard 3\u0026thinsp;+\u0026thinsp;7 group and 6 in the 3\u0026thinsp;+\u0026thinsp;7+V group) decided to apply allogeneic hematopoietic stem cell transplantation owing to the necessity and the financial reason.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 statistical analysis:\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePropensity-score matching was used to decrease confounding bias and selection bias, by matching the 3\u0026thinsp;+\u0026thinsp;7+V and the standard 3\u0026thinsp;+\u0026thinsp;7 cohorts in a 1:4 ratio using nearest-neighbor matching with calipers set to 0.2. The matching was based on a multivariate logistic regression model, which covariates were considered as age, Charlson comorbidity index and ELN risk category.\u003c/p\u003e \u003cp\u003eStatistical analysis was evaluated by Fisher\u0026rsquo;s exact test or ꭓ\u003csup\u003e2\u003c/sup\u003e test for categorical variables and Wilcoxon rank sum test for continuous variables at the p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 confidence level. The OS and EFS were estimated by the Kaplan-Meier method. Log-rank test and Cox proportional hazard modeling were used for the comparison. All the analysis were completed by R software package (version 4.5.0; R Development Core Team). Figures were painted by R 4.5.0 and GraphPad Prism 9.0.0.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. result","content":"\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003e3.1 the 3 + 7+V group versus the standard 3 + 7 group:\u003c/h2\u003e\n \u003cdiv\u003e\n \u003cp\u003eAs for the standard 3 + 7 group,100 patients were eligible for inclusion with 18 receiving idarubicin and 82 acquiring daunorubicin. We performed PSM for totally 100 patients in the standard 3 + 7 group and 22 patients in the 3 + 7+V group adjusting the age, ELN risk category and the Charlson comorbidity index. After PSM, 40 patients in the standard 3 + 7 group were unmatched (32.79%), leaving 82 patients (67.21%) for the final analysis. The median age was 55 years old and the median BM blast percentage was 69.8% at diagnosis in the 3 + 7 group versus 49.6 years old and 56% in the 3 + 7+V group. Female accounted for 55% and 40.9% respectively in two groups. As for ELN risk classification, 47.6% (3 + 7+V vs the 3 + 7 group:46.7% vs 50%), 28% (3 + 7+V vs the 3 + 7 group:25% vs 22.7%) and 24.4% (3 + 7+V vs the 3 + 7 group:28.3% vs 27.3%) of the patients were stratified as favorable, intermediate and adverse ranks respectively. Among them, 23.2% harbored \u003cem\u003eNRAS/KRAS\u003c/em\u003e mutation (3 + 7+V vs the 3 + 7 group:31.8% vs 20%),3.7% harbored \u003cem\u003etp53\u003c/em\u003e mutation (3 + 7+V vs the 3 + 7 group:0% vs 5%) and 14.6% harbored IDH1/2 aberrance (3 + 7+V vs the 3 + 7 group:27.3% vs 10%). (Table 1 summarized the characteristics of matched patients)\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003epatients’ demographics and clinical characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 + 7\u003c/p\u003e\n \u003cp\u003e(N = 60)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 + 7+V\u003c/p\u003e\n \u003cp\u003e(N = 22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0749\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.0\u003c/p\u003e\n \u003cp\u003e[15.0,63.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.5\u003c/p\u003e\n \u003cp\u003e[16.0,61.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharlson comorbidity index\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.688\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.00\u003c/p\u003e\n \u003cp\u003e[2.00, 7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.50\u003c/p\u003e\n \u003cp\u003e[2.00, 6.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eELN risk stratification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFavorable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (46.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBM blast\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.8\u003c/p\u003e\n \u003cp\u003e[21.5, 96.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.0\u003c/p\u003e\n \u003cp\u003e[20.5, 94.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMutations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (68.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eIDH1/2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eNRAS/KRAS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003etp53\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe CR/CRi rates were higher in the 3 + 7+V group than the standard 3 + 7 group, of 63.33% and 90.91% respectively(\u003cem\u003ep\u003c/em\u003e = 0.015), and the ORR was 68.33% and 90.91%(\u003cem\u003ep\u003c/em\u003e = 0.0468). 80% achieved MRD negative among patients reaching CR/CRi by engaging the 3 + 7+V group after one cycle of induction compared with 63.2% in the 3 + 7 group(\u003cem\u003ep\u003c/em\u003e = 0.241). As for patients with intermediate/adverse ELN risk classification AML, the CR/CRi rates could reach 81.82% in the 3 + 7+V group, compared with 43.75% in the standard 3 + 7 group (\u003cem\u003ep\u003c/em\u003e = 0.0394). The MRD negative rate among patients at favorable risk who reaching CR/CRi was inferior in the 3 + 7 group (3 + 7+V:100% vs 3 + 7:62.5%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.0331). There wasn’t significant distance in response rates when taking certain mutations or FAB categories into consideration which partly owing to the limited population. (Table 2 and Fig. 1 exhibited the response outcomes among some of the subgroups)\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eresponse outcomes with P \u0026lt; 0.05 highlighted by “*”\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 + 7\u003c/p\u003e\n \u003cp\u003e(N = 60)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 + 7+V\u003c/p\u003e\n \u003cp\u003e(N = 22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eresponse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0468*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (56.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR/CRi rates in different ELN risk groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFavorable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.309\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate/adverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(43.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0394*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCR/CRi rates when considering mutations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eTP53\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eIDH1/2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eNRAS/KRAS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMRD negative rate for patients reached CR/CRi\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(63.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEarly mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30-day mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eThe median OS wasn’t reached in each of the group. The estimated 1-year OS was 89.84% (95% CI:77.34%-100%) in the 3 + 7+V group and 84.81% (95% CI:75.60%-95.15%) in the 3 + 7 group. And the estimated 1-year EFS was 86.36% (95% CI:73.15%-100%) versus 49.31% (95% CI:38.02%-63.96%) respectively. The 3 + 7+V regimen prolonged the EFS (P = 0.0072), although the OS failed to distinguish significantly between two groups among univariable analysis (P = 0.62). (Fig. 2 demonstrated the survival curve).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAmong patients classified as adverse or intermediate ELN risk category, the estimated 1-year OS and EFS were 80.81% (95% CI:60.04%-100%) and 72.73% (95% CI:50.64%-100%) in the 3 + 7+V group versus 73.47% (95% CI:58.23%-92.69%) and 34.38% (95% CI:21.30%-55.48%) in the 3 + 7 group. It elaborated that the survival benefits still existed among patients classified as ELN adverse or intermediate risk group (EFS:\u003cem\u003eP\u003c/em\u003e = 0.033; OS:\u003cem\u003eP\u003c/em\u003e = 0.75). The OS and EFS for patients at favorable risk or with FAB M5 morphology illustrated different tendency between two treatment groups. (Fig. 3 demonstrated the survival curve according to different subgroups).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAs for the side effects, one death was observed within 30 days in the 3 + 7+V group because of sepsis. Grade ≥ 3 myelosuppression was observed in both the 3 + 7+V and the 3 + 7 groups, including thrombocytopenia (100% vs 100%), neutropenia (100% vs 100%) and anemia (100% vs 96.67%). The median nadir counts of blood cells during treatment were 46 (range:25–66) g/L versus 54 (range:33–81) g/L of hemoglobin (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01),0.00 (range:0-0.02) *10\u003csup\u003e9\u003c/sup\u003e/L versus 0.015 (range:0-0.5) *10\u003csup\u003e9\u003c/sup\u003e/Lof ANC (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01) and 3 (range:1–9) *10\u003csup\u003e9\u003c/sup\u003e/L versus 5 (range:1–14) *10\u003csup\u003e9\u003c/sup\u003e/L of platelet count (\u003cem\u003eP\u003c/em\u003e = 0.019) in the 3 + 7+V group and the 3 + 7 group respectively. Median duration of ANC \u0026lt; 0.5*10\u003csup\u003e9\u003c/sup\u003e/L was 20 (range:6–29) days in the 3 + 7+V group and 16.5 (range:3–33) days in the standard 3 + 7 group (\u003cem\u003eP\u003c/em\u003e = 0.161).\u003c/p\u003e\n \u003cp\u003eThe frequence of febrile neutropenia was 95.45% in the 3 + 7+V group and 95% in the 3 + 7 group. Sepsis was observed in 8 patients in the 3 + 7+V group of which 3 was evidenced by next-generation sequencing and 3 in the 3 + 7 group. The gastrointestinal disorders, notably performed as nausea or vomiting, were the most common nonhematologic adverse events expect for the infection. Reversible liver and kidney toxicity was observed in each of the groups. (Table 3 summarized the major nonhematologic toxicity)\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eMajor nonhematologic adverse events observed in treatment\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eNonhematologic adverse events\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3 + 7 group\u003c/p\u003e\n \u003cp\u003e(N = 60)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3 + 7+V group\u003c/p\u003e\n \u003cp\u003e(N = 22)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll Grades\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGrades ≥ 3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll Grades\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGrades ≥ 3\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFebrile neutropenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57 (95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57 (95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (95.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (95.45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocalized infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (91.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (91.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac disorders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (8.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (8.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArrhythmia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal disorders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (23.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNausea/vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (48.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (31.82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal obstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePancreatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRash\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (8.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypoxia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBronchopulmonary hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNervous system disorders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumbness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (11.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eInvestigations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAminotransferase increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (23.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood bilirubin increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (51.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003e3.2 the 2 + 5+V group versus the 3 + 7+V group:\u003c/h2\u003e\n \u003cdiv\u003e\n \u003cp\u003eFurthermore, we collected several contemporary data from patients receiving 3 + 7 regimen plus venetoclax and compared them with the 2 + 5+V group to try to explore the feasibility of the dose reduction of cytotoxic agents without impairing the efficiency.\u003c/p\u003e\n \u003cp\u003ePatients enrolled in the 2 + 5+V group was elder with the median age of 56 years old compared with 49.5 years old in the 3 + 7+V group (P = 0.0185). There were 8 females (42.1%) in the 2 + 5+V group compared with 9 (40.9%) in the 3 + 7+V group.73.7% patients were stratified as ELN intermediate/adverse risk in the 2 + 5+V group versus 50% in the 3 + 7+V group(P = 0.199). (Table 4 demonstrated the baseline information of two groups)\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003ebaseline characters of 3 + 7+V group and 2 + 5+V group with P \u0026lt; 0.05 highlighted by “*”\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3 + 7+V\u003c/p\u003e\n \u003cp\u003e(N = 22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2 + 5+V\u003c/p\u003e\n \u003cp\u003e(N = 19)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0185*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.5\u003c/p\u003e\n \u003cp\u003e[16.0, 61.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003cp\u003e[24.0, 73.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003esex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (57.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharlson comorbidity index\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.50\u003c/p\u003e\n \u003cp\u003e[2.00, 6.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.00\u003c/p\u003e\n \u003cp\u003e[2.00, 7.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eELN risk category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFavorable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (26.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (42.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBM blast percentage (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e[Min, Max]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.0\u003c/p\u003e\n \u003cp\u003e[20.5, 94.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.0\u003c/p\u003e\n \u003cp\u003e[4.50, 95.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMutations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (73.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eIDH1/2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eNRAS/KRAS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (31.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003etp53\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe CR/CRi rate was 84.21% in patients receiving the 2 + 5+V regimen and 90.91% in patients receiving 3 + 7+V (OR:0.990, P = 0.993). And the MRD negative rate among patients reaching CR/CRi was 93.75% in the 2 + 5+V group versus 80% in the 3 + 7+V group(P = 0.355). Among patients classified as ELN intermediate or adverse risk, the CR/CRi rates achieved 85.71% and 81.82% respectively. In the ELN favorable risk group, all patients reaching CR/CRi achieved MRD negative, regardless of the regimen selection. (Fig.\u0026nbsp;4\u0026nbsp;exhibited the odds ratios of failure to CR/CRi)\u003c/p\u003e\n \u003cdiv\u003e\n \u003cp\u003eWith a median follow-up duration of 274 days, the median OS and EFS were no reached in each of the groups. The 1-year estimated OS and EFS were 87.45% (95%CI:72.36%-100%) and 77.20% (95%CI:59.60%-100%) respectively in the 2 + 5+V group versus 89.84% (95%CI:77.34%-100%) and 86.36% (73.15%-100%) in the 3 + 7+V group. The OS (P = 0.81) and the EFS (P = 0.31) weren’t significantly distinct between two groups under univariate analysis. (Fig. 5 showed the survival curve between two groups) The selection of regimen still failed to differ the OS (HR:0.398, P = 0.457) and the EFS (HR:0.695, P = 0.677) when considered age and ELN risk rank as confounding factors. (Fig. 6 showed the hazard ratio of age, ELN risk rank and the regimen for OS and EFS)\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAll patients suffered from grade ≥ 3 myelosuppression in the 2 + 5+V group and the 3 + 7+V group, including thrombocytopenia (100% vs 100%), neutropenia (100% vs 100%) and anemia (94.74% vs 100%).The median duration of ANC \u0026lt; 0.5*10\u003csup\u003e9\u003c/sup\u003e/L was 17 days (range:5–25 days) in the 2 + 5+V group and 20 days (range:6–29 days) in the 3 + 7+V group respectively (P = 0.113).The frequence of febrile neutropenia was 84.21% in the 2 + 5+V group and 95.45% in the 3 + 7+V group(P = 0.321).\u003c/p\u003e\n \u003cp\u003eOne patient from each group died within 30 days because of sepsis. 31.58% patients were considered to experience sepsis in the 2 + 5+V groups compared with 36.36% in the 3 + 7+V group. Expect for the infection, the gastrointestinal disorders were the most common nonhematologic adverse events. None of the patients in 2 + 5+V group suffered grade ≥ 3 gastrointestinal disorder compared with 3 in the 3 + 7+V group. Besides, liver and kidney toxicity appeared more serious in the latter group. Grade ≥ 3 heart failure was detected in 4 cases in each of the group. (Table 5 summarized the major nonhematologic toxicity)\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 5\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003ethe nonhematologic toxicity between two groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eNonhematologic adverse events\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3 + 7+V group\u003c/p\u003e\n \u003cp\u003e(N = 22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2 + 5+V group\u003c/p\u003e\n \u003cp\u003e(N = 19)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll Grades\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGrades ≥ 3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll Grades\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGrades ≥ 3\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (31.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (31.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocalized infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (63.16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (52.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac disorders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (26.32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (21.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArrhythmia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGastrointestinal disorders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNausea/vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (31.82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (31.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal obstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePancreatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRectal perforation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRash\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeadache\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eInvestigations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAminotransferase increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (36.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (21.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood bilirubin increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (63.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (52.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCardiac troponin I increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003e3.3 supplement:\u003c/h2\u003e\n \u003cdiv\u003e\n \u003cp\u003eWe suppled three additional cases in which the 2 + 5+V regimen was administrated as reinduction therapy when the disease relapsed for the first time. All of them achieved CR/CRi again after receiving the 2 + 5+V reinduction and two of them even reached MRD negative, indicated that the regimen may come across part of the resistance mechanism and be efficient to relapsed leukemia. (Fig. 7 demonstrated the response and long-term survival of these three patients and the other 19 cases of new diagnosed AML as mentioned before in the 2 + 5+V group)\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eCompared with the standard 3\u0026thinsp;+\u0026thinsp;7 group, the CR/CRi rates were higher in the 3\u0026thinsp;+\u0026thinsp;7+V group (90.91% vs 63.33%, P\u0026thinsp;=\u0026thinsp;0.015) with 80% undetectable MRD in all of these responded cases, indicating that the 3\u0026thinsp;+\u0026thinsp;7+V regimen can bring more considerable and deeper remission to patients with new diagnosed AML. Besides, the 3\u0026thinsp;+\u0026thinsp;7+V regimen, by engaging which the estimated 1-year OS and EFS could reach 89.84% and 86.36% respectively, appeared favor to prolonged EFS (P\u0026thinsp;=\u0026thinsp;0.0072). The superiority causing by 3\u0026thinsp;+\u0026thinsp;7+V regimen still existed among patients classified as ELN adverse or intermediate risk group.\u003c/p\u003e \u003cp\u003eBoth the hematologic toxicity and the nonhematologic adverse events of the 3\u0026thinsp;+\u0026thinsp;7+V regimen showed more severe though the duration of neutrophile granulocyte recovery wasn\u0026rsquo;t extremely expended. One patient died for sepsis within 30 days after therapy administration in the 3\u0026thinsp;+\u0026thinsp;7+V group and no early mortality was observed in the standard 3\u0026thinsp;+\u0026thinsp;7 group. 8 patients developed sepsis by using the 3\u0026thinsp;+\u0026thinsp;7+V regimen, compared with 3 in the 3\u0026thinsp;+\u0026thinsp;7 group. Gastrointestinal disorders were the most common nonhematologic side effect in each of the groups in line with previous researches. The liver and kidney toxicity were reversible in both groups.\u003c/p\u003e \u003cp\u003eFurthermore, we tried to explore the feasibility of engaging 2\u0026thinsp;+\u0026thinsp;5+V regimen for reducing the adverse events without impairing efficiency. The median age of the 2\u0026thinsp;+\u0026thinsp;5+V group was 56 (range:24\u0026ndash;73) years old with 36.84% aged 60 years old or older compared with 49.5 years old (range:16\u0026ndash;61) years old (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0185) with only 4.45% aged 60 years old or older in the 3\u0026thinsp;+\u0026thinsp;7+V group. Besides, 73.7% patients were stratified as ELN intermediate/adverse risk in the 2\u0026thinsp;+\u0026thinsp;5+V group versus 50% in the 3\u0026thinsp;+\u0026thinsp;7+V group(P\u0026thinsp;=\u0026thinsp;0.199). The CR/CRi rates showed no significantly difference between two groups (90.91% vs 84.21%, OR:0.990, P\u0026thinsp;=\u0026thinsp;0.993). Besides, 93.75% among the responded patients achieved MRD negative in the 2\u0026thinsp;+\u0026thinsp;5+V group compared with 80% in the 3\u0026thinsp;+\u0026thinsp;7+V group (P\u0026thinsp;=\u0026thinsp;0.355). In the former group, the 1-year estimated OS and EFS were 87.45% (95%CI:72.36%-100%) and 77.20% (95%CI:59.60%-100%) respectively. The alternation of regimen failed to demonstrate survival benefit in both univariate and multivariate analysis.\u003c/p\u003e \u003cp\u003eCompared with the 3\u0026thinsp;+\u0026thinsp;7+V group, the median duration of neutropenia (17 days vs 20 days) and the frequence of febrile neutropenia (84.21% vs 95.45%) were lower in the 2\u0026thinsp;+\u0026thinsp;5+V group and the nonhematologic toxicity was slighter. The gastrointestinal disorders were better tolerated in the latter group. Thus, the dose reduction of cytotoxic agents was feasible, especially for patients with heart diseases considering the cardiac toxicity caused by anthracycline cumulated.\u003c/p\u003e \u003cp\u003eInspired by the less toxicity and considerable efficiency in treating ineligible patients with untreated AML, [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] venetoclax added to hypomethylating agents (HMA) started to be used as induction regimen to fit AML patients. The reported CR/CRi rate was approximate 81%-89%, superiority to the traditional 3\u0026thinsp;+\u0026thinsp;7 regimen,[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] similar with the response rates on the 3\u0026thinsp;+\u0026thinsp;7+V or 2\u0026thinsp;+\u0026thinsp;5+V regimen. Besides, previous researches reported that the 3\u0026thinsp;+\u0026thinsp;7 regimen favored to patients at favorable/intermediate risk or with FAB M5 morphology relative to venetoclax plus HMA.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]In our analysis, venetoclax induced deeper remission in patients at favorable risk and demonstrated numerically incremental benefits of the CR/CRi rates and survival prolongation to both favorable risk and FAB M5 AML. And the optimum wasn\u0026rsquo;t impaired by the reduction of cytotoxic agents.\u003c/p\u003e \u003cp\u003eMoreover, we supplied three relapsed AML cases and all of them reached CR/CRi by administrating the 2\u0026thinsp;+\u0026thinsp;5+V regimen as reinduction therapy, implying the potential of the regimen to eliminate the resistant leukemic cells.\u003c/p\u003e \u003cp\u003eThere were still lots of limitation in the study. Due to the small population, we failed to analyze the outcome between patients harboring different mutations, such as \u003cem\u003eIDH2\u003c/em\u003e, which was demonstrated to be benefit from venetoclax previously. [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] And the response rates were analyzed only after receiving one course of induction. Besides, the bias and the detriment to generalizability were inevitable for the single-center retrospective study. Therefore, larger, muti-center and prospective studies will be required.\u003c/p\u003e \u003cp\u003eOverall, the addition of venetoclax to the standard 3\u0026thinsp;+\u0026thinsp;7 induction therapy could notably improve the outcome of newly diagnosed AML patients. And the comparable efficiency with considerable security by administrating 2\u0026thinsp;+\u0026thinsp;5+V regimen, consisting of idarubicin for 2 days, cytarabine for 5 days and venetoclax for 7 days, make it possible to substitute for the 3\u0026thinsp;+\u0026thinsp;7+V regimen as induction treatment, especially for elder patients.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAML Acute myeloid leukemia\u003c/p\u003e\n\u003cp\u003eANC Absolute neutrophil count\u003c/p\u003e\n\u003cp\u003eBM Bone morrow\u003c/p\u003e\n\u003cp\u003eCR Complete remission\u003c/p\u003e\n\u003cp\u003eCRi Complete remission with incomplete hematologic recovery\u003c/p\u003e\n\u003cp\u003eEFS Event-free survival\u003c/p\u003e\n\u003cp\u003eELN European Leukemia Net\u003c/p\u003e\n\u003cp\u003eHR Hazard ratio\u003c/p\u003e\n\u003cp\u003eNCCN National Comprehensive Cancer Network\u003c/p\u003e\n\u003cp\u003eNR No response\u003c/p\u003e\n\u003cp\u003eMRD minimal residual disease\u003c/p\u003e\n\u003cp\u003eOR Odds ratio\u003c/p\u003e\n\u003cp\u003eORR Overall response rate\u003c/p\u003e\n\u003cp\u003eOS Overall survival\u003c/p\u003e\n\u003cp\u003ePLT Platelet\u003c/p\u003e\n\u003cp\u003ePR Partial remission\u003c/p\u003e\n\u003cp\u003ePSM Propensity score matched\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eThis research study was approved by the Ethics Committees of the Institute of Hematology \u0026amp; Blood Diseases Hospital (approval number: IIT2021028-EC-1) and informed consent was obtained from all patients. All procedures adhered to the principles outlined in the Declaration of Helsinki. None of the patients\u0026rsquo; name or other personal information was disclosed.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eData availability:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The data that support the findings of this study are available from the corresponding author (Ying Wang) upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declared no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis study was supported by Tianjin Key Medical Discipline Construction Project under Grant TJYXZDXK-3-001A.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor Contributions:\u003c/p\u003e\n\u003cp\u003eConceptualization, methodology and funding acquisition: Ying Wang. Supervision: Shuning Wei. Writing-original draft preparation, writing-review and editing and formal analysis: Qiaoyi Zhou. Investigation: Hong Liu. Project administration: Hong Liu, Lihua Wu，Chunhua Liu，Xiyan Wang，Zhenzhen Wang，Lijun Fang, Runxia Gu, Shuning Wei.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eWe thank the patients and the staff.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eD\u0026ouml;hner H, Bloomfield WD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep;17(12):1152.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiNardo CD, Pullarkat JB, Thirman V, Garcia MJ, Wei JS, Konopleva AH, D\u0026ouml;hner M, Letai H, Fenaux A, Koller P, Havelange E, Leber V, Esteve B, Wang J, Pejsa J, H\u0026aacute;jek V, Porkka R, Ill\u0026eacute;s K, Lavie \u0026Aacute;, Lemoli D, Yamamoto RM, Yoon K, Jang SS, Yeh JH, Turgut SP, Hong M, Zhou WJ, Potluri Y. 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Clin Exp Med. 2023 Jun;23(2):227.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShort NJ, Qiao VS, Kadia W, Ravandi TM, Macaron F, Dinardo W, Daver CD, Konopleva N, Borthakur M, Shpall G, Popat EJ, Champlin U, Mehta RE, Al-Atrash R, Oran G, Jabbour B, Garcia-Manero E, Issa G, Montalban-Bravo GC, Yilmaz G, Maiti M, Kantarjian A. H, Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure. J Hematol Oncol, 2022 Jan 29. 15(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiNardo CD, Quaglieri TI, MacRaild A, Loghavi S, Brown S, Thijssen FC, Pomilio R, Ivey G, Salmon A, Glytsou JM, Fleming C, Zhang SA, Ma Q, Patel H, Kornblau KP, Xu SM, Chua Z, Chen CC, Blombery X, Flensburg P, Cummings C, Aifantis N, Kantarjian I, Huang H, Roberts DCS, Majewski AW, Konopleva IJ, Wei M. Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood. 2020 Mar;12(11):803.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"AML, Venetoclax, chemotherapy, older patients","lastPublishedDoi":"10.21203/rs.3.rs-8657162/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8657162/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThere were several explorations to combine venetoclax with standard 3\u0026thinsp;+\u0026thinsp;7 regimen or modified intensive chemotherapy. However, few of them included direct comparisons between different regimens.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThe study retrospectively collected the information about newly diagnosed AML patients of which 100 induced by the standard 3\u0026thinsp;+\u0026thinsp;7 regimen, 22 by the 3\u0026thinsp;+\u0026thinsp;7+ventoclax regimen and 19 by the 2\u0026thinsp;+\u0026thinsp;5+ventoclax regimen. We performed propensity score-matched analysis to the 3\u0026thinsp;+\u0026thinsp;7+ventoclax group and the historical standard 3\u0026thinsp;+\u0026thinsp;7 group to adjust age, Charlson comorbidity index and ELN risk category. Furthermore, we tried to explored the feasibility of the 2\u0026thinsp;+\u0026thinsp;5+venetoclax regimen to adapt for the older or patients with more complication by comparing to the 3\u0026thinsp;+\u0026thinsp;7+venetoclax group.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eCompared with the standard 3\u0026thinsp;+\u0026thinsp;7 therapy, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was higher in the 3\u0026thinsp;+\u0026thinsp;7+venetoclax group (90.91% vs 63.33%, p\u0026thinsp;=\u0026thinsp;0.015) and the event-free survival (EFS) was prolonged (P\u0026thinsp;=\u0026thinsp;0.0072). Besides, venetoclax induced deeper remission for patients at ELN favorable risk. The superiority causing by 3\u0026thinsp;+\u0026thinsp;7+V regimen still existed among patients classified as ELN adverse or intermediate risk group. 36.84% of the 2\u0026thinsp;+\u0026thinsp;5+ventoclax group aged 60 years old or older. There was no significant difference in CR/CRi rate, OS or EFS between the 2\u0026thinsp;+\u0026thinsp;5+venetoclax group and the 3\u0026thinsp;+\u0026thinsp;7+venetoclax group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe addition of venetoclax to the standard 3\u0026thinsp;+\u0026thinsp;7 induction therapy could notably improve the outcome of untreated AML. And the comparable efficiency with considerable security by administrating 2\u0026thinsp;+\u0026thinsp;5+venetoclax regimen, make it possible to substitute for the 3\u0026thinsp;+\u0026thinsp;7+V regimen as induction treatment, especially for elder patients.\u003c/p\u003e","manuscriptTitle":"Venetoclax combined with modified intensive chemotherapy in newly diagnosed acute myeloid leukemia: a propensity score-matched analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 12:56:23","doi":"10.21203/rs.3.rs-8657162/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e74cb85-1f20-432b-86f2-0fb66f240772","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Withdrawn","date":"2026-05-13T07:44:29+00:00","index":"","fulltext":""},{"type":"decision","content":"Revision requested","date":"2026-04-30T07:08:11+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T08:01:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 12:56:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8657162","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8657162","identity":"rs-8657162","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}