Intensified Induction Chemotherapy with Regimen Containing Intermediate Dose Cytarabine for De Novo Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 943-943
Author(s):  
Jianxiang Wang ◽  
Yingchang Mi ◽  
Jiazhuo Liu ◽  
Mingwei Fu ◽  
Ying Wang ◽  
...  

Abstract Abstract□F Objective To analyze the complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) of de novo acute myeloid leukemia (AML) patients induced with HAD (Homoharringtonine-HHT, cytosine arabinoside-AraC, daunorubicin-DNR) regimen containing intermediate dose AraC (ID-AraC) and to explore the impact of cytogenetic abnormalities on the prognosis. Methods 87 AML patients were treated with HAD regimen containing ID-AraC as induction therapy. HAD regimen was as follow: HHT 2mg/m2.d, Day 1–7; Ara-C 100mg/m2, Day 1–4, 1–1.5g/m2/q12h, Day 5–7; DNR 40 mg/m2.d, Day 1–3. CR rate, DFS and OS were calculated.83 patients who had karyotype results were divided into 3 groups according to SWOG criteria respectively. Differences in CR rate, DFS and OS among different groups were evaluated. Results The CR rate of the 87 cases was 80/87 (92%). Median DFS of the 80 CR patients was NR (not reach). DFS rates at 1 and 3 years were 76.3% and 63.4% respectively. The median OS of the 87 patients was 16 (range from 2 to 67) months. OS rates at 1 and 3 years were 86.0% and 58.7% respectively. According to SWOG criteria, CR rate, median DFS and OS were 100%, NR for the favorable group„dG88.9%, NR and 16 months for the intermediate group„dG83.3%, 4.5 months and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. Conclusions HAD regimen containing ID-AraC as induction chemotherapy regimen is very effective in de novo AML of adult patients, can achieve higher CR rate and longer survival time than standard dose HAD regimen. Most of the patients were able to endure therapy. Cytogenetics is the important prognostic factor for AML patients. The differences among the three groups were statistically significant.

2009 ◽  
Vol 84 (7) ◽  
pp. 422-427 ◽  
Author(s):  
Jiazhuo Liu ◽  
Yingchang Mi ◽  
Mingwei Fu ◽  
Wenjuan Yu ◽  
Ying Wang ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4595-4595
Author(s):  
Jianxiang Wang ◽  
Yingchang Mi ◽  
Yangping Xue ◽  
Wenjuan Yu ◽  
Shougeng Bian

Abstract 243 untreated de novo acute myeloid leukemia (AML) patients were treated with (homoharringtonine+AraC, HA) based induction therapy which composing of three chemotherapeutic drugs (HAD, HAM, HAA, HAE) in our hospital for recent 12 years. Complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) of the patients were calculated. 184 patients who had karyotype results were divided into four groups according to SWOG (Southwestern Oncology Group) criteria. Differences of CR rate, DFS and OS of different groups were evaluated. The CR rate of all 243 cases was 77.4%, and 94.6% out of them were for 1~2 courses. Median DFS of the 188 CR patients was 28.5 (range from 1.0 to 153) months. DFS rates at 3 years and 5 years were 45.4%, 40.2% respectively. The median OS of 243 patients was 18.4 (range from 0.5 to 154) months. OS rates at 3 years and 5 years were 36.9%, 31.4% respectively. CR rate, DFS and OS of the different cytogenetic risk groups were also be analyzed. According to SWOG criteria, patients were classified into favorable, intermediate, adverse and unknown groups. CR rate, median DFS and OS were 97.8%, 87.4 months and 89.0 months in favorable group; 81.9%, 17.6 months and 22.3 months in intermediate group; 61.5%, 9 months and 11.5 months in the adverse group; 79.3%, 29.0 months, 19.9 months in the unknown group, respectively. The differences among the four groups were statistically significant. Multivariates analyses confirmed contribution of cytogenetics and courses of post-remission chemotherapy to DFS and OS. If we incorporated unknown group into the intermediate group, the CR rate is 80.6%. DFS rates at 3 years and 5 years were 40.5%, 38.1% respectively. OS rates at 3 years and 5 years were 40.3%, 37.4% respectively. We conclude triple-drugs induction regimens based on HA are highly effective in adult AML in China. Cytogenetics is the important prognostic factor. SWOG karyotype subtyping criteria is appropriate to our patients and unknown group can be incorporated into the intermediate group.


2020 ◽  
Author(s):  
Na Wang ◽  
Kanchun Dai ◽  
Aakash Desai ◽  
Bei Ge ◽  
Weihong Lin ◽  
...  

Abstract Background: Acute myeloid leukemia(AML) is a highly heterogeneous hematological malignancy. Despite, increase in treatment options for AML over the past decade, prognosis for AML remain dismal. Numerous prognostic models have been developed for this disease, however nomograms predicting long-term survival in AML patients after induction chemotherapy(IA regimen) have not been described.Method: We constructed nomograms to predict disease-free survival(DFS) and overall survival(OS) by analyzing the cohort of patients with de novo non-M3 AML patients who underwent induction chemotherapy between June 2008 to August 2019. We utilized univariable and multivariable Cox proportional hazards regression analyses to obtain the selected variables for the nomograms. The discriminative ability and calibration were tested using C statistics, calibration plots, and Kaplan-Meier curves.Results: A total of 360 patients who underwent induction chemotherapy with IA regimen were included in the study. Of these 55% were male with a median age was 48 years. Using the univariate and multivariate analyses, the following variables were identified in the prediction of DFS: age(HR, 1.770; 95%CI, 1.160-2.702; P = 0.008), Hb(HR, 0.634; 95%CI, 0.462-0.870; P = 0.005), albumin(HR, 0.473; 95%CI, 0.363-0.615; P < 0.001) and cyto/molecular risk group(intermediate vs. favorable: HR, 1.614; 95%CI, 1.128-2.309; P = 0.001; poor vs. favorable: HR, 2.459; 95%CI, 1.645-3.676; P < 0.001) at the time of diagnosis, and allo-HSCT treatment(HR, 0.341; 95%CI, 0.234-0.497; P < 0.001). Factors which predicted OS were Hb (HR, 0.616; 95%CI, 0.438-0.866; P = 0.005), albumin (HR, 0.448; 95%CI, 0.340-0.591; P < 0.001), cyto/molecular risk group (intermediate vs. favorable: HR, 1.558; 95%CI, 1.068-2.275; P = 0.021; poor vs. favorable: HR, 2.348; 95%CI, 1.523-3.620; P < 0.001), allo-HSCT treatment (HR, 0.256; 95%CI, 0.166-0.396; P < 0.001), and age (HR, 1.528; 95%CI 0.980-2.382; P = 0.061). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.715 for DFS and 0.731 for OS). Conclusion: Independent predictors of survival and relapse risk after IA regimen for AML can be utilized to obtain survival nomograms. These nomograms were able to predict DFS and OS while having good calibration accuracy and discriminative ability on internal validation.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2000-2000 ◽  
Author(s):  
Shigeki Ohtake ◽  
Shuichi Miyawaki ◽  
Hiroyuki Fujita ◽  
Hitoshi Kiyoi ◽  
Katsuji Shinagawa ◽  
...  

Abstract We conducted a multicenter prospective randomized study to determine whether the intensified daunorubicin (DNR) induction chemotherapy would be as effective as idarubicin (IDR) in adult acute myeloid leukemia (AML). Newly diagnosed adult patients with AML excluding FAB-M3 were consecutively registered and randomized to receive either increased dose of DNR or standard dose of IDR induction chemotherapy. All patients received cytarabine 100mg/m2 daily for 7 days by continuous intravenous infusion, and either DNR 50mg/m2 daily for 5 days or IDR 12mg/m2 daily for 3 days according to randomization. If the patients did not achieve complete remission (CR) after the first induction therapy, the same induction therapy was given once more. Patients achieving CR were again randomized to receive either 3 courses of high-dose cytarabine or 4 courses of conventional multiagent consolidation therapy. The results of later randomization will be reported another abstract. From December 2001 to December 2005, 1064 newly diagnosed patients with de novo AML were registered and 1057 were eligible. Median age was 47 years old (range 15 to 64). Five hundred twenty five patients were randomized to DNR group, and 532 to IDR group. The two groups were well matched for pretreatment characteristics. CR was achieved in 407 patients (77.5%; 95% CI, 73.9% – 81.1%) with 321 (61.1%) after 1 induction course in DNR group and 418 patients (78.6%; 75.1% – 82.1%) with 341 (64.1%) after 1 course in IDR group (p = 0.68). Patients receiving IDR took slightly but significantly longer to recover from neutropenia and thrombocytopenia. There was a higher rate of sepsis in IDR (8.7%) than DNR (4.9%) (p = 0.02). The early death within 60 days occurred in 25 patients (4.7%) in IDR and 11 (2.1%) in DNR (p = 0.03). Logistic regression analysis revealed that induction regimen was not the independent prognostic factor, but CBF leukemia and the percentage of peroxidase positive leukemic blast were the significant independent factors for achieving remission. There was also no significant difference between the groups in the longer-time measures of efficacy: estimated overall survival at 4 years was 49.1% (42.4% – 55.8%) for DNR and 53.1% (47.6% – 58.6%)for IDR (p = 0.37); estimated relapse free survival at 4 years from CR was 42.2% (36.1% – 48.3%) for DNR and 41.8% (35.9% – 47.7%) for IDR (p = 0.62). The Cox proportional hazards analyses showed that the induction regimen did not affect these outcomes. In conclusion, increased dose of DNR and standard dose of IDR both achieve high remission rate and good long-term efficacy, and are equally effective for the treatment of AML patients up to 64 years, although the final assessment will have to be performed after longer follow up.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5240-5240
Author(s):  
Shaowei Qiu ◽  
Dong Lin ◽  
Hui Wei ◽  
Guangji Zhang ◽  
Chunlin Zhou ◽  
...  

Abstract Objects: Investigate the clinical characteristics and factors of the impact on the survival of FLT-ITD mutation in the acute myeloid leukemia(AML) with intermediate chromosome karyoptye. Methods: We retrospectively collected and analyzed information regarding clinical characteristics and survival data from 133 patients with newly diagnosed AML with FLT3-ITD mutation and intermediate chromosome karyoptye from 2001-2015.The median follow-up time was 13.02 months. Results: 1. The median age was 37, median WBC was 50×109/L , the incidence between male and female was similar, the most common FAB subtype was M5(60.2%), the hepatosplenomegaly incidence was 8.4% . 2.The complete remission (CR) was 64.5% after first induction chemotherapy. CR could reached 74.4% or 57.1% when induction regimen included the medium dose cytarabine(100mg/m2 d1-4;1g/m2 q12h d5-7) or standard dose cytarabine(Ara-C)(100mg/m2d1-7) respectively(p=0.063). 3. Totally 131 patients received chemotherapy, and subsequently 22 patients received transplantation after chemotherapy. When the patients only received chemotherapy, 3-year OS was 39.9%, 3-year DFS was 44.8% and while in the patients who received transplantation, 3-year OS was 73.5%, 3-year DFS was 77.5%, the outcome was better (p<0.05). 4. Univariable analysis showed that OS was related with age, hepatosplenomegaly, transplantation, WBC, the remission of induction chemotherapy. DFS was related with transplantation, courses for CR. Cox regression showed that transplantation and remission of induction chemotherapy were the independent prognosis factor. When the patient only received chemotherapy, FACS-MRD persisted negative was the independent prognosis factor. Conclusions: The FLT3-ITD de novo AML patients with intermediate chromosome karyoptye had unique characteristics. The patients who attained CR after induction chemotherapy and received transplantation would get better outcome, while in the patients who only received chemotherapy, FACS-MRD persisted negative implied better outcome. The induction regimen that contained medium Ara-C could reach higher CR , that may translated into better survival, therefore it may be the appropriate choice for FLT3-ITD AML patients. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2006 ◽  
Vol 109 (6) ◽  
pp. 2314-2321 ◽  
Author(s):  
Draga Barbaric ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Soheil Meshinchi ◽  
Nyla A. Heerema ◽  
...  

Abstract To assess the impact of minimally differentiated acute myeloid leukemia (AML-M0) morphology in children, we analyzed 2 sequential Children's Cancer Group AML clinical trials. We compared presenting characteristics and outcomes of 82 CCG-2891 and CCG-2961 patients with de novo, non–Down syndrome (DS) AML-M0 with those of 1620 patients with non-M0 AML, and of 10 CCG-2891 patients with DS-associated AML-M0 with those of 179 with DS-associated non-M0 AML. Morphology and cytogenetics were centrally reviewed. The non-DS AML-M0 children had a lower white blood cell (WBC) count (P = .001) than their non-M0 counterparts and a higher incidence of chromosome 5 deletions (P = .002), nonconstitutional trisomy 21 (P = .027), and hypodiploidy (P = .002). Outcome analyses considering all children with non-DS AML demonstrated no significant differences between M0 and non-M0 patients. Analyses restricted to intensive-timing CCG-2891 and CCG-2961 demonstrated comparable complete response (CR) rates (79% and 78%) between non-DS M0 and non-M0 patients. Overall survival (OS) from diagnosis (38% ± 14% versus 51% ± 3%; P = .160) was not significantly different between the 2 groups. OS from end of induction (45% ± 17% versus 63% ± 3%; P = .038), event-free survival (EFS; 23% ± 11% versus 41% ± 3%; P = .018), and disease-free survival (DFS; 31% ± 14% versus 52% ± 3%; P = .009) were inferior in the M0 group. There was no significant outcome difference between DS-associated AML-M0 and non-M0 children. This study suggests that intensively treated non–DS-associated AML-M0 children have an inferior outcome compared with children with non-M0 AML.


Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.


Author(s):  
Yu-Hung Wang ◽  
Chien-Chin Lin ◽  
Chia-Lang Hsu ◽  
Sheng-Yu Hung ◽  
Chi-Yuan Yao ◽  
...  

AbstractExpression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.


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