The Survival Of The Elderly Acute Myeloid Leukemia Patients Do Not Depend On The Intensity Of Induction Chemotherapy. Retrospective Study Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5029-5029
Author(s):  
Sebastian Grosicki ◽  
Ewa Bodzenta ◽  
Marek Kriegler ◽  
Ilona Szypula ◽  
Marcin Fejklowicz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Standard Dose ◽  
Study Results ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Abstract The aims of this study were comparison of overall survival (OS) and complete remission rate (CR) in whole group of acute myeloid leukemia (AML) >60 patients, and in younger older (61 – 70) AML patients in dependency of qualification to risk group according to PALG stratification and a schedule of treatment. Patients with AML >60 after diagnosis were qualified into the risk groups according to PALG stratification for AML >60. The patients from group 1 patients were receiving intensive induction chemotherapy DAC (daunorubicin, cytarabine, cladribine) or DA (daunorubicin, cytarabine), those from group 2 were receiving cytarabine+thioguanine induction chemotherapy, and those from group 3 chemotherapy with low doses of cytarabine. Patients from first group, who reached CR after induction were receiving consolidation with mitoxantrone + standard dose of cytarabine, and next they were qualified to HSCT or maintenance phase. Patients from group 2 and 3 independently of results of induction were receiving successive cycles of chemotherapy like in first course every 4 weeks to 2 years with very intensive supportive care. One hundred sixteen patients with untreated AML treated In period 02.2009-12.2012, age 73 (61-89), men 50% were included to this study. Thirty three patients were qualified to group 1, 50 to second and 33 to third. After preliminary analysis, because of similar early and late outcomes of the therapy in group 2 and 3, those groups of patients were joint for next analysis. Disclosures: No relevant conflicts of interest to declare.

Time from Hospital Admission to Induction Chemotherapy Adversely Affects Outcomes in Patients with Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1289-1289 ◽  
Author(s):  
Hossein Maymani ◽  
Bilal Ahmad ◽  
Michael G Machiorlatti ◽  
Sara K. Vesely ◽  
Samer A Srour ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Hospital Admission ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Risk Status ◽  
Group 2 ◽  
Wbc Count ◽  
Oklahoma Health ◽  
Acute Myeloid ◽  
Group 1

Abstract Background: The duration of time from the diagnosis of acute myeloid leukemia (AML) to the initiation of chemotherapy is dependent on multiple factors. Previous studies suggest that delays in the time from diagnosis to treatment do not impact overall survival (OS) and complete remission (CR). As a result, awaiting laboratory analysis of molecular targets for therapy, specifically FLT3, has become more commonly adopted by clinicians. However, this strategy can lead to significant delays in initiation of chemotherapy. The aim of this study is to analyze the impact of delaying chemotherapy on OS and CR in AML patients. Methods: We performed a retrospective analysis on adult patients with AML who were treated with induction chemotherapy at The University of Oklahoma Health Sciences Center from January 2000 to June 2012. Time from admission to treatment (TAT) was calculated from the date of admission to the date of initiation of chemotherapy. In addition, we analyzed the admission day of the week and its association with TAT (days). Association between CR and TAT was assessed using ANOVA and Chi-Square tests. Kaplan-Meier estimates of median OS were calculated for groups defined by categorical variables. A Cox Proportional Hazards model on OS was implemented using TAT, age, risk status (favorable, intermediate and unfavorable risks), day of admission, distance to hospital, and white blood cell (WBC) count. Interaction was assessed and a backward selection procedure was used to find the covariates associated with OS. Statistical analysis was performed using SAS 9.3 software. Results: A total of 160 patients with AML received induction chemotherapy at our institution during the defined time, with 137 meeting inclusion criteria. The median age at diagnosis was 51 years with 63.7% being male and 36.3% being female. Of these patients, 77.0% were white, 10.6% African American, 6.2% Native American and 3.7% Hispanic. The median TAT for all patients was 3.0 days. There were 116 (84.7%) patients treated within 0-4 days (Group 1) and 21 (15.3%) patients treated beyond 4 days (Group 2). Patients in Group 1 had a median survival of 252.5 days compared to those in Group 2 of 188.5 days (p = 0.0958) when analyzed univariately. Multivariable analysis demonstrated TAT of 0-4 days was independently related to OS with a hazard ratio of .604 (95% CI 0.369-0.990, p = 0.0451). The CR rate for Group 1 was 69.8% compared to Group 2 of 54.6% (p = 0.0692). In addition, patients admitted on a weekday (Monday-Friday) were more likely to initiate chemotherapy within 0-4 days as compared to patients admitted on the weekend (Saturday-Sunday) with a p = 0.0102. Conclusion: AML patients treated more than 4 days following admission have decreased OS and a trend toward decreased rate of CR as compared to patients treated within 0-4 days. This finding is independent of age, risk status, WBC count, and distance to hospital. Also, patients admitted on the weekend were more likely to experience delays in initiating chemotherapy compared to those admitted on the weekday. Although a larger sample size and testing in other clinic settings needs to be done to confirm this relationship, this study suggests treating AML patients within 4 days of hospital admission may be associated with improved outcomes. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Daunorubicin Dose Intensification for Induction Therapy in Acute Myeloid Leukemia Patients with FLT3-ITD Mutants

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4033-4033
Author(s):  
Eun-Ji Choi ◽  
Je-Hwan Lee ◽  
Jung-Hee Lee ◽  
Han-Seung Park ◽  
Sun-Hye Ko ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
High Dose ◽  
Dose Intensification ◽  
Acute Myeloid

Abstract Background Patients with FLT3-ITD mutated acute myeloid leukemia (AML) have generally poor survival. Recent update of ECOG trial comparing standard- vs. high-dose daunorubicin showed that daunorubicin dose intensification improved survival in AML with FLT3-ITD mutants (Blood 2016;127:1551). In subgroup analysis of our previous randomized trial, high-dose daunorubicin seemed to be more effective than idarubicin in AML patients with FLT3-ITD mutants (ASH abstract No. 2535, 2015). In this retrospective investigation, we aimed to evaluate the role of daunorubicin dose intensification for induction therapy in AML patients with FLT3-ITD mutants who were treated at a single institute. Methods We analyzed data from 120 patients of newly diagnosed FLT3-ITD mutated AML patients who received induction chemotherapy between January 2002 and March 2016. The regimens consisted of high-dose daunorubicin (HD-DN, 90 mg/m2/d x 3d, n=39), standard-dose daunorubicin (SD-DN, 45 mg/m2/d x 3d, n=48), or idarubicin (IDA, 12 mg/m2/d x 3d, n=33) in combination with cytarabine (200 mg/m2/d x 7d). Patients with acute promyelocytic leukemia were not included. Results After the first round of induction chemotherapy, 53 patients had persistent leukemia; 50 received the second round of induction chemotherapy consisting of daunorubicin (45 mg/m2/d x 2d) or idarubicin (8 mg/ m2/d x 2d) in addition to cytarabine (200 mg/m2/d x 5d) and 3 received other regimens. A total of 81 patients achieved CR, and the CR rates were 76.9%, 58.3%, and 69.7% in HD-DN, SD-DN, and IDA, respectively (P=0.175). The 4-year cumulative incidence of relapse (CIR) of these 81 patients was 48.8%. With the median follow-up duration of survivors of 59.9 months (range, 4.6-170.7), 4-year overall survival (OS) and event-free survival (EFS) were 57.1%/27.7%/35.7% (P=0.025) and 45.2%/23.9%/36.0% (P=0.042) in HD-DN, SD-DN, and IDA, respectively. HD-DN showed statistically higher OS (hazard ration [HR], 0.424; P=0.005) and EFS (HR, 0.497; P=0.01), and lower CIR (P=0.036) than SD-DN, while OS and EFS differences between HD-DN and IDA were not statistically significant. Conclusion Daunorubicin dose intensification for induction therapy seemed to be effective in AML patients with FLT3-ITD mutants. Further studies are needed to investigate whether HD-DN is superior to IDA in this population. Considering high relapse rate, combination strategies of daunorubicin dose intensification and targeted agents such as FLT3 inhibitors should be developed. Disclosures No relevant conflicts of interest to declare.

Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.

1996 ◽  
Vol 14 (5) ◽  
pp. 1521-1525 ◽  
Author(s):  
C P Steuber ◽  
J Krischer ◽  
T Holbrook ◽  
B Camitta ◽  
V Land ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Drug Regimen ◽  
Childhood Acute Myeloid Leukemia ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

PURPOSE A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML). PATIENTS AND METHODS One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. RESULTS Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. CONCLUSION The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.

Validation of Monosomal Karyotype Based Model In the Risk Stratification of Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2745-2745
Author(s):  
Murtadha K. Al-Khabori ◽  
Karen Yee ◽  
Vikas Gupta ◽  
Aaron Schimmer ◽  
Andre Schuh ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Stratification ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Structural Abnormality ◽  
Complex Karyotype ◽  
Poor Risk ◽  
Monosomal Karyotype ◽  
Acute Myeloid

Abstract Abstract 2745 Background: The influence of cytogenetic abnormalities on the prognosis of acute myeloid leukemia (AML) has been well-documented; however, the relative impact of certain miscellaneous abnormalities remains controversial. Recently, monosomal karyotype-based risk stratification has been shown to further discriminate the prognosis within the poor-risk karyotype group (Breems et al. JCO 2008), but this finding requires further validation. Methods: We retrospectively reviewed 779 consecutive adult AML patients treated with standard induction chemotherapy, consisting of daunorubicin plus cytarabine (3+7), at our institution from 1998–2008. After excluding patients with favourable risk, normal, missing or failed karyotype, 290 patients remained and were included in the analysis. Results: The baseline characteristics of these 290 patients were as follows: median age 59 y (range 18–81), male 181, prior malignancy 110, median white cell count (WBC) 7.6 × 10^9/L (range 0–246). The karyotypic features included single monosomy in 42, 2 or more monosomies in 51, and non-monosomy structural and numerical abnormalities in 197 patients. Of the 290, 116 (40 %) had three or more abnormalities (complex karyotype, CK). A total of 141 patients (49 %) achieved complete remission (CR) with 3+7 induction chemotherapy. Sixty-four patients received allogeneic stem cell transplantation in CR. The median overall survival (OS) for all patients was 12 months (95% CI: 10–14 months). The median OS was 10 (95% CI: 6–18), 7 (95% CI: 6–10) and 14 months (95% CI: 12–16) in the single monosomy, 2+ monosomy and non-monosomy groups, respectively (p < 0.0001 by log-rank test comparing the three groups). Among the patients containing at least one monosomy, the OS was not significantly different between the CK and non-CK groups (p = 0.08 by log rank). Similarly, in the non-monosomy structural abnormality group, the OS was not significantly different between the CK and non-CK groups (p = 0.2). Conclusions: Our results provide validation for the monosomal karyotype-based risk stratification for AML, indicating that patients with at least one monosomy have an inferior OS compared to other poor-risk non-monosomy groups. Within each of the monosomy and non-monosomy groups, the presence of a complex karyotype does not significantly influence the OS. Disclosures: No relevant conflicts of interest to declare.

NPM1, IDH1/2 and DNAH11 Gene Mutations Can Improve a Prognostic Stratification of Acute Myeloid Leukemia Patients with Normal Karyotype but Not Harboring FLT3/ITD Mutation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2534-2534
Author(s):  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Dennis Dong Hwan Kim ◽  
Chul Won Jung ◽  
Jun-Ho Jang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Adult Patients ◽  
Npm1 Mutation ◽  
Group 3 ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Abstract Abstract 2534 Background: Acute myeloid leukemia with normal karyotype (AML-NK) is known to be heterogeneous in the molecular level. Accordingly, it has become more critical to dissect this group of patients according to their prognosis using a molecular genetic technology. We attempted to analyze the incidence and prognostic implication of genetic abnormalities on survival in 426 adult patients with AML-NK. Methods: A total of 67 AML-NK patients achieved complete remission (CR), candidate mutations in 21 genes were identified by whole exome sequencing which has 41–89× coverage and by single-nucleotide polymorphism array analysis using marrow mononuclear cells at diagnosis of AML-NK. Subsequently, mutation analysis of 11 genes (i.e. FLT3/ITD, NPM1, DNMT3a, IDH1, IDH2, TET2, NRAS, WT1, DNAH11, SF3B1, and PHF6) which are known to be involved in the pathogenesis of hematologic diseases, were performed using Sanger sequencing in another subset of 359 AML-NK patients as a validation cohort. Results: Of 426 patients in total (median age: 51, ranges: 15–85), FLT3/ITD, NPM1, and DNMT3a mutations were associated with higher leukocytes counts at presentation of AML-NK. In 284 patients who received standard remission induction (RI) chemotherapy (excluding 119 patients with conservative treatment and 22 early death/1 follow-up loss after RI chemotherapy), those with FLT3/ITD mutation were significantly associated with a higher risk of relapse (p=0.02), a shorter leukemic-free survival duration (LFS)(p<0.01) or overall survival (OS) (p=0.01). Accordingly, we divided the patients into FLT3/ITD+ and FLT3/ITD− population, and analyzed their treatment outcomes according to the other mutations. In the FLT3/ITD− group (n=200), those with NPM1 mutation showed a higher CR rates after one or two cycles of RI chemotherapy (p<0.01) and a longer OS duration (p<0.01), hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.25–0.73, adjusted by other clinical variables including age, leukocyte counts at diagnosis, and transplantation (Figure 1). In the FLT3/ITD+ patients (n=84), NPM1 mutation was found to be a favorable prognostic factor showing a lower relapse rate (p=0.00), a longer LFS duration (p<0.01, HR 0.35, 95% CI 0.18–0.70), and OS duration (p=0.04, HR 0.55, 95% CI 0.31–0.98) in NPM1 mutated patients. In addition, OS was significantly different in favor of those with IDH2, especially R140Q IDH2 mutation, (p=0.04, HR 0.30, 95% CI 0.09–0.99), whereas DNAH11 mutation was associated with inferior OS (p<0.01, HR 5.78, 95% CI 1.65–20.25). Accordingly, we stratified the FLT3/ITD+ patients into three subgroups according to the NPM1, IDH1/2 and DNAH11 mutation status, Group 1: NPM1 mutation and IDH1 or 2 mutations (n=16), Group 2: isolated DNAH11 mutation (n=4) and Group 3: all mutations were negative (n=64). The group 1 showed significantly better OS than group 2 (p<0.01, HR 16.90, 95% CI 3.48–82.15) or group 3 (p<0.01, HR 3.40, 95% CI 1.20–9.55) (Figure 2). In a subgroup analysis of younger patients less than 60 years of age, similar outcomes were also observed in favor of group 1 in terms of OS (data not shown). Conclusion: Our study confirmed that NPM1 mutation is an independent prognostic factor in adult patients with AML-NK not harboring FLT3/ITD mutation. In addition, several other genetic markers were identified as prognostic including IDH1/2 or DNAH11 mutations as well as NPM1 mutation in a subgroup of AML-NK patients with FLT3/ITD mutation. Disclosures: No relevant conflicts of interest to declare.

Multidrug-Related Protein 1 (MRP1) Polymorphisms rs129081, rs212090, and rs212091 Predict Survival In Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2580-2580 ◽  
Author(s):  
Desiree Kunadt ◽  
Christian Dransfeld ◽  
Maria Schmiedgen ◽  
Michael Kramer ◽  
Christoph Röllig ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Significant Influence ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Npm1 Mutation ◽  
Significant Difference ◽  
Impact On Treatment ◽  
Acute Myeloid

Abstract Background ABCB1 (=MDR1, multidrug resistance protein 1) single nucleotide polymorphisms (SNPs) were shown to have a significant impact on therapy outcome in patients with acute myeloid leukemia (AML). Furthermore, an independent significant impact on treatment response and patient survival of SNPs in the genes for ABCC4 (MRP4), ABCC5 (MRP5) and ABCC11 (MRP8) related SNPs has also been demonstrated. In contrast, therapeutic strategies trying to modulate the anthracycline efflux of these transporters have failed in most clinical trials so far. Recently, higher dosages of daunorubicin used during induction chemotherapy have been associated with a better outcome in certain subgroups of AML patients. Hence, in times of individual diagnostic genetic analyses available as point-of-care diagnostics, the goal of this study was to further investigate whether SNPs in ABC-transporter genes, which are responsible for anthracycline efflux, have an independent impact on treatment outcome. Patients and Methods DNA samples were obtained from bone marrow aspirates of 160 Caucasian patients with newly diagnosed AML as part of the prospective AML2003 trial (NCT00180102). The cohort solely consisted of patients with a normal karyotype, based on conventional G-banding, minimizing false results in case of gain or loss of chromosomal material. All patients received double induction chemotherapy with daunorubicin and cytarabine. After DNA extraction, quantitative real time PCR was performed, using a total of 49 SNP assays investigating SNPs of seven different ABC genes. The identification of the corresponding SNPs was performed in an in silico analysis using the NIH dbSNP database and HapMap while statistical univariate and multivariate analyses were performed using SPSS. Results We detected three ABCC1 (MRP1) SNPs: rs129081 (CACCCC[C/G]ACTCCA), rs212090 (TTACTG[A/T]TCCCAC), and rs212091 (ACCTTA[A/G]AGAACA) with a significant influence on disease-free survival (DFS) or overall survival (OS), respectively. Patients carrying the homozygous rs129081 GG-SNP had a significant longer 5-year OS and 5-year DFS compared to the homozygous wildtype CC and heterozygous CG patients (OS: 68% [GG] vs. 40% [CC] vs. 64%, [CG], p=.035; DFS: 64% vs. 35% vs. 50%, p=.01). SNP rs212090 revealed a statistically significant difference in DFS when comparing homozygous alleles TT and AA (wildtype), 40% vs. 68%, p=.021. SNP rs212091 showed a significant difference concerning OS, with homozygous SNP GG leading to worse OS (0% vs. wildtype AA 64% vs. heterozygous AG 59%, p=.006). Again, there was a significant difference in DFS between both homozygous alleles AA (wildtype) and GG (55% vs. 0%, p=.018). Furthermore, there were no significant differences of standard clinical and laboratory baseline characteristics, FLT3-ITD mutation, or NPM1-mutation status, or chemotherapeutic toxicities. In order to exclude false positive findings of SNPs conferred as a result of leukemic transformation, we obtained saliva germline DNA from patients in complete remission who were treated by chemoconsolidation and performed a confirmatory analysis with the investigated SNPs, including rs129081, rs212090, and rs212091. Here, all SNPs were shown to be expressed in germline DNA in remission and bone marrow samples at diagnosis alike. The multivariate models for rs129081, rs212090 (TT), rs212091(AG), and rs212091(AA) revealed significances of p=.024, p=.029, p=.042, and p=.017 respectively for DFS but not for OS (except for rs212091[AA]). After adjustment for a false discovery rate of 5% still a trend towards the association of the SNPs and DFS could be seen. Therefore, more research is necessary to strengthen this evidence. Conclusion In this study we found a significant influence of rs129081, rs212090, and rs212091 SNPs (ABCC1, MRP1) on survival in AML in univariate analyses. Interestingly, these polymorphisms were not associated with other AML specific characteristics at diagnosis and were shown to be expressed in germline DNA and AML DNA alike. Hence, we suggest a prognostic effect of these SNPs which might be responsible for differential anthracycline susceptibility. Disclosures: No relevant conflicts of interest to declare.

High Expression of Mir-15a Predicts Shorter Survival and Worse Response to Chemotherapy in Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5330-5330 ◽  
Author(s):  
Aleksandra Butrym ◽  
Dagmara Baczynska ◽  
Andrzej Tukiendorf ◽  
Justyna Rybka ◽  
Tadeusz Dobosz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Reverse Transcriptase ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Aberrant Expression ◽  
Risk Of Death ◽  
Response To Chemotherapy ◽  
Acute Myeloid

Abstract Background: MicroRNAs (miRNAs) are small non-coding RNA molecules, that control gene expression by targeting messenger RNA (mRNA), via degradation or suppression of translation. Aberrant expression of microRNAs (miRs) has been proved to have a role in acute myeloid leukemias (AML) The aim of the study was to determine expression of miR-15a in acute myeloid leukemia patients before and after chemotherapy and its influence on patient clinical outcome. Methods: miRNAs from isolated leukemic cells were extracted using mirVanaTM miRNA Isolation kit (Ambion Inc., Carlsbad, CA, USA) following the manufacturer's protocol. Reverse transcriptase (RT) reactions were performed for mature miRNA cDNA synthesis in separate tubes using specific stem-loop RT primers and TaqMan® MicroRNATM Reverse Transcription kit (Applied Biosystems, Foster City, CA, USA). After microRNA isolation, reverse transcriptase reactions were performed, followed by cDNA amplification. The relative amount of microRNA-15a was normalized according to the reference RNU48 level. Results were considered statistically significant with p-value < 0.05. Results: 95 patients (aged 60.2 ± 15.0, 22–90, Male = 61%) with newly diagnosed AML were included into the study. Samples of the bone marrow for miR-15a expression analysis were collected before start of chemotherapy and repeated after completed induction chemotherapy (40 patients). A control group of 20 matched patients was also taken into account. The analyzed group consisted of: 7 patients with AML M0, 34 had M1, 29 had M2, 14 had M4 and 11 had M5. AML patients has higher miR-15a expression than control group (p=0.005633). The risk of death in AML patients was higher in patients with higher miR-15a expression on diagnosis (p=0.0430), Fig.1. Patients with lower miR-15a expression were more likely to achieve complete remission after induction chemotherapy (p=0.0130). After successful chemotherapy we observed significant drop in miR-15a expression. Conclusions: We proved that miR-15a was upregulated in AML patients and its expression influenced remission achieving and death risk. Figure 1. Survival of AML patients depending on miR-15a expression. Figure 1. Survival of AML patients depending on miR-15a expression. Disclosures No relevant conflicts of interest to declare.

scholarly journals High IDH1 Expression Is Associated with a Poor Prognosis in Cytogenetically Normal Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5314-5314 ◽  
Author(s):  
Qiu-Ling Ma ◽  
Jing-Han Wang ◽  
Yun-gui Wang ◽  
Chao Hu ◽  
Qi-Tian Mu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Strong Association ◽  
Gene Mutations ◽  
Micro Rna ◽  
Acute Myeloid

Abstract ABSTRACT The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations, and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of micro-RNA 181 family. Prognosis was adversely affected by high IDH1 expression with shorter overall survival (OS) and event free survival (EFS) in the context of clinical characteristics including age, WBC, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2, and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of OS, EFS and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1expression is associated with a poor prognosis of CN-AML. Disclosures No relevant conflicts of interest to declare.

Nonanthracycline Induction Chemotherapy (T-FLAG) for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4356-4356
Author(s):  
Amit Mahipal ◽  
Emmanuel C. Besa ◽  
Anne Marie Valorie-Oberlie ◽  
Isaac Matthias ◽  
Adam Thode
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Free Survival ◽  
Related Mortality ◽  
Acute Myeloid

Abstract Abstract 4356 Introduction: Prognosis of elderly patients (age>60 years) with acute myeloid leukemia (AML) is poor as compared to younger patients with a higher incidence of cardiac co-morbidities. With standard induction therapy, complete remission (CR) is achieved in 35% to 50% of elderly patients. However, the induction anthracycline containing chemotherapy related mortality is in this population has been reported to be approximately 30%. We attempted to decrease this by replacing the anthracycline with topotecan. Alternative therapies are needed that are less toxic but equally efficacious. In a phase I/II trial of the combination of topotecan, fludarabine, cytarabine and G-CSF (T-FLAG) in elderly AML and MDS, there was 50% CR and 15% treatment related deaths. In this study, we report patients >60 years of age treated with T-FLAG as an initial therapy for AML at our institute. Methods: We retrospectively reviewed the charts of elderly patients with AML treated with T-FLAG at our institution. Elderly patients were defined as more than 60 years of age. IRB approval was obtained for the study. All patients received topotecan 2mg/m2, fludarabine 30 mg/m2, and cytarabine 2000 mg/m2 all given over 30 min from day 1 to day 4 and G-CSF 400 μ g/m2/day from the day 5 to neutrophil counts recovery. International working group criteria was used to assess responses. All statistical analysis was done using SAS statistical software. Descriptive statistics were used. Progression free survival was defined from the time of diagnosis to progression, death or last follow up, whichever comes first. Overall survival and progression free survival was calculated using Kaplan and Meier method. Results: Thirteen elderly patients were treated with T-FLAG. The median age of diagnosis was 73 years (Range: 60–86 years). There were 10 male and 3 female patients. Ten (77%) patients had complex cytogenetics. Cardiomyopathy (EF <50%) or elevated liver function tests precluding anthracycline use was present in 54% of the patients. Response rate was 69% with 7 (54%) patients achieving CR and 2 (15%) patients achieving partial remission. Out of 10 patients with abnormal cytogenetics at baseline, 7 (70%) patients had cytogenetic CR. Eleven (85%) patients were alive at day 30. Median progression free survival and overall survival was 36 weeks and 54 weeks respectively. The median time for the recovery of neutrophil counts (>500/μ L) was 22 days (Range: 10–47 days). Conclusions: In this study of unfavorable risk group elderly patients, T-FLAG induction chemotherapy results in comparable remission rates with low induction chemotherapy related mortality. It may be an alternative regimen for elderly patients with complex cytogenetics or patients who cannot tolerate anthracyclines. More studies are needed to confirm these results. This however, may be useful to bridge patients to transplant or maintenance demethylating agents to improve survival. Disclosures: No relevant conflicts of interest to declare.

Acute Myeloid Leukemia: Longterm Outcome Predicted by Age and Genetic Groups

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1509-1509
Author(s):  
Thomas Buchner ◽  
Wolfgang E. Berdel ◽  
Utz Krug ◽  
Claudia Haferlach ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Multivariable Analysis ◽  
High Dose ◽  
Genetic Groups ◽  
Longterm Outcome ◽  
Acute Myeloid

Abstract Abstract 1509 Introduction: Both, patients' age and genetic groups are important predictors of outcome in AML while their influence remains poorly quantified and compared. Methods: In the AMLCG (Acute Myeloid Leukemia Cooperative Group) 1999 trial 1470 patients (pts) were 16–59y and 1747 pts were 60–85y of age. 95% of pts could be classified according to genetic risk groups as standardized on behalf of the ELN (Blood 2010;115:453-74). Their treatment was randomized between TAD-HAM versus HAM-HAM induction (TAD, standard dose thioguanine, cytarabine, daunorubicin 60mg/m2 × 3; HAM, high-dose cytarabine 3g/m2 × 6, mitoxantrone 10mg/m2 × 3), TAD consolidation and monthly maintenance vs TAD and autologous SCT, any chemotherapy + vs – G-CSF priming. All assignment was done upfront. Pts of <60y received routine double induction and full dose HAM while pts of 60+y preferentially received only 1 course induction and HAM at 1g instead of 3g cytarabine/m2 × 6. Results: With little difference according to randomizations, pts <60y and 60+y achieved a complete remission (CR) rate of 65% and 51% (p<.001), a 5y overall survival (OS) of 41% and 14% (p<.001), and a 5y ongoing remission duration (RD) of 47% and 21% (p<.001). We particularly focussed on pts around 60y of age and compared the 231 pts of 57–59y with the 315 pts of 60–62y. Corresponding to their similar age the two groups showed similar baseline characteristics. In contrast and due to the cutoff point for age adaption at 60y they differed considerably in treatment. Expressed by the cumulative dosage of cytarabine in induction and early consolidation, the difference between the two groups was by factor 3.9. This difference, however, did not translate into a different outcome being 60% vs 57% CR (p=0.59), 28% vs 25% 5y OS (p=0.40) and 32% vs 29% RD at 5y (p=0.46). Through focussing on patients around 60y a relevant influence of chemotherapy intensity and age adaption could thus be excluded. A multivariable analysis in the complete patients between 16 and 85y of age identified genetic groups and age (as a continuous variable) to be the only risk factors predicting CR, OS as well as RD whereas other risk factors such as secondary AML, WBC, and LDH were predictive only for subsets of endpoints. Among all treatment variables only HAM-HAM induction was associated with a slightly superior RD (p= 0.0715). Grouping by age resulted in 4 age categories (16–46y:n=683, 47–59y: n=787, 60–66y: n=815, and 67+y: n=932) with significantly different OS as well as RD. Subdividing by genetic groups (favorable: n=593, intermediate I: n=1169, intermediate II: n=526, adverse: n=780) distinguished 3 significantly different categories (favorable, intermediate, adverse), a pattern observed in all age groups. Conclusion: In a defined representative population of pts with AML the longterm outcome was mainly determined by age and genetic groups but not by treatment intensity or variables, nor by other prognostic factors. Both, age and genetic groups should thus contribute to a reliable prediction of outcome in AML. Disclosures: No relevant conflicts of interest to declare.

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