Prognostic Impact of MLL Partial Tandem Duplication in Acute Myeloid Leukemia of Intermediate Cytogenetic Risk: A Subgroup Analysis of Cetlam Protocol 2003 & 2012

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2514-2514
Author(s):  
Marta Pratcorona ◽  
Ana Garrido ◽  
Salut Brunet ◽  
Jordi Esteve ◽  
María Camino Estivill ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Risk Groups ◽  
Complete Response ◽  
Prognostic Impact ◽  
Free Survival ◽  
Molecular Alterations ◽  
Tandem Duplications ◽  
Acute Myeloid

Abstract Background Cytogenetics at diagnosis is the most important prognostic factor in acute myeloid leukemia (AML). Of note, intermediate cytogenetic risk group (IR-AML) is a very heterogeneous subset including normal karyotypes and all the cytogenetic abnormalities not included in the favorable or the adverse groups. Molecular alterations affecting NPM1, FLT3 and CEBPA show a prognostic impact in IR-AML. MLL partial tandem duplications (MLL-PTD) have also been described in this group of AML, but their prognostic impact have not been well established. Aim To analyze the prognostic relevance of MLL-PTD in the subset of patients diagnosed with IR-AML since 2003, and included in the CETLAM protocols LMA-2003 and LMA-2012. Methods Between 2003 and 2004 MLL-PTD were analyzed by Southern Blot (enzymes employed BglII, EcoRI, BamHI). Since 2004, a long PCR strategy was used to identify this abnormality. Results NPM1 mutations (NPM1mut), FLT3 internal tandem duplications (FLT3-ITD) and MLL-PTD were available for 893 patients. No MLL-PTD was found among 111 and 161 patients of the good and poor cytogenetic risk groups, respectively. The IR-AML group included 621 patients, and 37 carried a MLL-PTD (6%), thus only this cytogenetic group of patients was analyzed. NPM1mut were found in a 41% of patients and none of them had a concomitant MLL-PTD (p<0.001). FLT3-ITD were found in a 31% of patients, and 14 patients had also an MLL-PTD. No correlation between MLL-PTD and age, leukocyte count, and percentage of blasts in bone marrow was found. There was a significant association with gender: men were more frequently mutated than women (29 vs 8; p=0.001). Regarding outcome of IR-AML, leukemia-free survival (LFS) was significantly higher for patients without MLL-PTD (5-year LFS 44±3% vs 18±8%; p<0.001), and overall survival (OS) was also better for this subgroup of patients (5-year OS 42±2% vs 20±7%; p=0.004). There were no differences in the complete response rate, but patients with MLL-PTD had a higher risk of relapse (cumulative incidence at 5 years 39 vs 74%, p=0.000151). Among patients with MLL-PTD, no differences were observed depending on the concurrence of FLT3-ITD. When only patients with NPM1 wild-type were considered, MLL-PTD maintained a significantly poor prognostic impact (36±3% vs 21±7%; p=0.009). Conclusions MLL-PTD is a genetic alteration found in a 6% of IR-AML. Patients with this abnormality have a worse LFS and OS than the rest of patients of the IR-AML group. Based on these results, patients with MLL-PTD should be considered as patients with poor cytogenetic risk AML for treatment allocation. Disclosures No relevant conflicts of interest to declare.

Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4505-4511 ◽  
Author(s):  
Verena Ingeborg Gaidzik ◽  
Richard Friedrich Schlenk ◽  
Simone Moschny ◽  
Annegret Becker ◽  
Lars Bullinger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Serum Lactate Dehydrogenase ◽  
Study Group ◽  
Prognostic Impact ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Myeloid

AbstractTo evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Group protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos.

Trisomy 8 in the Light of Recent Cytogenetic Classification Advances. A Study From the French Acute Myeloid Leukemia Intergroup.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2594-2594 ◽  
Author(s):  
Nicolas Boissel ◽  
Christine Terré ◽  
Pascale Cornillet-Lefebvre ◽  
Odile Maarek ◽  
Eric Lippert ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Gene Mutation ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Prognostic Impact ◽  
Trisomy 8 ◽  
Factors Associated ◽  
Acute Myeloid ◽  
Similar Incidence

Abstract Abstract 2594 Poster Board II-570 Background: Trisomy 8 (+8) is one of the most common cytogenetical abnormality observed in acute myeloid leukemia (AML). The prognostic impact of +8 as sole aberration remains unclear and +8 may be classified either within intermediate- or high-risk subgroups. Recently, the prognostic impact of cytogenetic in AML has been refined by the identification of: 1) favorable genotypes in cytogenetically normal (CN) AML defined by the presence of either NPM1 gene mutation (NPM1m) or CEBPA gene mutation (CEBPAm) and the absence of FLT3 duplication (FLT3/ITD); 2) highly unfavorable AML with monosomal karyotype (MK). The aim of this study was to precise the prognostic impact of: 1) additional +8 in various cytogenetic risk subgroups; and 2) +8 as sole aberration when compared to different CN-AML genotypes. Patients: A total of 2087 patients with AML (AML-M3 excluded) were treated in the LAM-2001, LAM-SA-2002, ALFA-9802 and ALFA-9801 studies from the French AML Intergroup. After central review, cytogenetic analysis was considered successful in 1796 patients. Abnormalities were categorized according to the French AML Intergroup classification. All analysis (complete remission, CR; overall survival, OS; probability of continuous complete remission, %CCR) were stratified on studies. Results: +8 was present in 171/1796 (9.5%) with a similar incidence among the different cytogenetic subgroups: 22/243 fav-risk (9.1%), 99/1121 int-risk (8.8%), and 50/432 unfav-risk (11.6%). The incidence of +8 was significantly higher in MK-AML versus non MK-AML (30/223, 13.5%, p=.04). In none of these subgroups (fav, int, unfav, and MK), the presence of +8 was associated with a significantly different outcome (CR, OS, %CCR). When compared to patients with CN-AML, the 78 patients with +8 as sole anomaly had a similar age, a lower WBC (median WBC: 5 G/L vs 11.5 G/L, p=.004), a similar incidence of FLT3/ITD (22.2% vs 23.7%, 6/27 vs 101/426, p=.99), and a lower incidence of NPM1m (23.8% vs 46.5%, 5/21 vs 187/402, p=.05). In patients with +8 as sole anomaly, prognostic factors associated with a shorter OS were age (p=.01), high WBC (p=.01), and presence of +8 in all analyzed metaphases which was found in 1/3 of patients (p=.05). In those patients, when compared to CN-AML in general, CR rate was similar (88% vs 87%, p=.99), but %CCR and OS were shorter without, however, reaching significance (5y-%CCR: 31.8% vs 45.7%, p=.18). When compared to CN-AML patients with favorable genotypes (NPM1m or CEBPAm w/o FLT3/ITD), patients with +8 as sole anomaly had now a lower CR rate (87% vs 93%, p=.13) and significantly shorter %CCR and OS (5y-%CCR: 37.4% vs 57.8%, p=.05; 5y-OS 35.6% vs 59.0%, p=.05). Conversely, the prognosis of patients with +8 as sole anomaly appeared similar to that of patients with CN-AML w/o favorable genotypes (5y-OS: 32.6%). Conclusion: We report here the largest cohort of patients with +8. Additional +8 is equally distributed among cytogenetic risk subgroups and does not impact prognosis in each of these subgroups. Patients with AML with +8 as sole anomaly have an outcome comparable to that of CN-AML without favorable genotypes, suggesting that these patients should be managed similarly. Disclosures: No relevant conflicts of interest to declare.

The Activator of Transcription 3 (STAT3) Gene Polymorphisms Are Associated with Treatment Outcomes In Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4858-4858
Author(s):  
Bao-An Chen ◽  
Yue-jiao Zhong ◽  
Ji-feng Feng ◽  
Lu Cheng ◽  
Yufeng Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chinese Population ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Strong Relationship ◽  
Cellular Transformation ◽  
Janus Kinase ◽  
Nucleotide Polymorphisms ◽  
Free Survival ◽  
Acute Myeloid

Abstract Abstract 4858 Objectives: In the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway signaling pathway, the STAT3 is one of the most prominent predictable factors for cancer and leukemia. STAT3 activation might promote cellular transformation and therefore have an important role in human tumors. This study was aimed to investigate the relationship between the STAT3 polymorphisms and the treatment responses of AML in the Chinese population. Methods: We tested three single nucleotide polymorphisms (SNPs) with 130 Acute Myeloid Leukemia (AML) patients. Genomic DNA was isolated from peripheral blood and assayed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). Results: The results showed there were strong relationship between unfavorable cytogenetic, partial remission (even no remission) and the frequencies of GG genotype in rs9909659 (P=0.01 and 0.03) and the patients less than 45 years old was significant association with GA/AA genotype (P=0.01). But associations were not confirmed about event-free survival and leukemia-free survival in the Chinese population studied. Conclusions: It is clear that the AML patients with GG genotype in rs9909659 are not sensitive to standard chemotherapy method Disclosures: No relevant conflicts of interest to declare.

Fludarabine, Cytarabine, and Attenuated-Dose Idarubicin (m-FLAI) Induction for Elderly Patients with Acute Myeloid Leukemia: Results of a Multicenter Phase II Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3626-3626
Author(s):  
Yoojoo Lim ◽  
Youngil Koh ◽  
Sung-Soo Yoon ◽  
Seonyang Park ◽  
Byoung Kook Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Phase Ii ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Free Survival ◽  
Induction Regimen ◽  
Acute Myeloid

Abstract Abstract 3626 Introduction: Although there have been remarkable improvements in treatment of acute myeloid leukemia (AML), the prognosis of AML in elderly patients remains poor, and the best induction chemotherapy for these patients remains yet unknown. To devise an effective induction regimen for elderly patients with AML, we conducted a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in these patients. Patients and Methods: Elderly (60 years or older) AML patients who did not receive previous chemotherapy were enrolled. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen was comprised of fludarabine (25mg/m2, days 1–4), cytarabine (1000mg/m2, days 1–4), and attenuated-dose idarubicin (5mg/m2, days 1–3). The primary end point was complete remission (CR) rate. Results: A total of 108 patients (median age 68.4 years, M:F=64:44) were enrolled. CR was achieved in 62.9% of patients, and treatment-related mortality rate (TRM) was 25.8%. Median overall survival (OS) was 9.3 months, and median event-free survival (EFS) was 6.6 months. The mortality at 30 and 60 days was 18% and 24%, respectively. Performance status and comorbidity did not have prognostic value in these patients. Bone marrow expression of CD117 was related to long EFS and OS. Conclusion: In conclusion, m-FLAI is a safe and effective induction regimen for previously untreated AML in elderly patients. Bone marrow CD117 expression is an independent good prognostic factor in these patients. (ClinicalTrials.gov number, NCT01247493) Disclosures: No relevant conflicts of interest to declare.

DNMT3A mutations Predict for Inferior Outcome in NPM1-Wildtype and Molecular Unfavorable Cytogenetically-Normal Acute Myeloid Leukemia: A Study of the German-Austrian AMLSG

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 415-415 ◽  
Author(s):  
Verena I. Gaidzik ◽  
Richard F. Schlenk ◽  
Peter Paschka ◽  
Anja Stölzle ◽  
Andrea Corbacioglu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Epigenetic Modification ◽  
Methylation Status ◽  
Prognostic Impact ◽  
Sequencing Analysis ◽  
Mutational Status ◽  
Acute Myeloid

Abstract Abstract 415 Background: Alteration of DNA methylation, a hallmark of epigenetic modification, is currently discussed as one important pathomechanism in leukemogenesis. Using a next-generation sequencing approach, a frameshift mutation of the gene encoding the DNA methyltransferase (DNMT3A) in an acute myeloid leukemia (AML) case was identified. DNMT3A catalyses the addition of a methyl group to the cytosine residue of CpG dinucleotides, thereby affecting promoter methylation status and gene expression. Subsequent sequencing analysis in an independent cohort of 288 AML patients (pts) revealed DNMT3A mutations (DNMT3Amut) in 22% of the pts; mutations were associated with intermediate-risk cytogenetics and poor outcome. Aims: To evaluate frequency and clinical impact of DNMT3Amut in pts with AML aged 18 to 61 years who were treated within AMLSG treatment trials AML HD98A (Schlenk et al., J Clin Oncol 2010;28:4642–8) and AMLSG 07–04 (NCT00151242). Methods: DNMT3A mutation analysis was performed in 1218 AML (HD98A, n=685; AMLSG 07–04, n=533; de novo AML, n=1102; s-AML, n=45; t-AML, n=69) using a DNA-based PCR assay for all coding exons (1 to 23) followed by direct sequencing. The median follow-up was 5.06 years. Results: DNMT3A mut were found with an overall frequency of 19.6% (239/1218); 189 mutations were located in the MTase domain clustering at amino acid R882 (79%). All but one mutation were heterozygous; only 4 cases had two mutations. DNMT3A sequence alterations included 17 frameshift, 4 nonsense, and 222 missense mutations. DNMT3A mut pts were significantly older (P=.01), more frequently females (P=.001), had higher white blood cell and platelet counts (both P<.0001), and higher bone marrow blasts percentage (P=.001). DNMT3Amut were associated with cytogenetically-normal AML (CN-AML, P<.0001), while DNMT3Amut were rare in favorable and adverse-risk karyotypes (P<.0001). Correlations with other molecular markers (NPM1, CEBPA, FLT3, IDH1/2, TET2, ASXL1) revealed a significant association with NPM1 (P<.0001), FLT3-ITD (P<.0001), and IDH1/2 (IDH1R132, P<.0001; IDH2R140, P=.0003; IDH2R172, P=.03) mutations, while co-occurrence of CEBPA (P=.02) and ASXL1 (P=.02) mutations was less frequent. DNMT3A mutational status did not impact complete remission (CR) rate, event-free (EFS) and relapse-free survival (RFS), neither in the whole cohort (P=.09, P=.98, P=.11; respectively) nor in the subgroup of CN-AML (P=.39, P=.79, P=.19, respectively). DNMT3Amut had a negative impact on overall survival (OS) in trend in the whole cohort (P=.07) and significantly in CN-AML (P=.02). In multivariable analyses, DNMT3Amut were in trend associated with a negative prognostic impact on OS (hazard ratio, 1.24; P=.06). In addition, we performed subgroup analyses according to (1) the NPM1 mutational status, and (2) the molecular risk groups of CN-AML (as defined by the European LeukemiaNet classification). DNMT3Amut did not impact OS in NPM1-mutated patients in the whole cohort as well as in CN-AML (P=.34; P=.22; respectively), while in NPM1-wildtype patients DNMT3Amut were associated with inferior OS in both, the whole cohort and in CN-AML (P=.001; P=.005; respectively). In molecular unfavorable CN-AML (NPM1-wildtype with or without FLT3-ITD, NPM1-mutated with FLT3-ITD, CEBPA-wildtype), DNMT3Amut were significantly associated with worse OS (P=.002) compared with DNMT3A-wildtype pts, even outweighing FLT3-ITD as an unfavorable prognostic marker. There was no effect of DNMT3Amut in molecular favorable-risk CN-AML. Conclusions: DNMT3A mutations are confirmed as frequent genetic aberrations in AML, associated with normal karyotype, NPM1, FLT3-ITD, and IDH1/2 mutations. DNMT3Amut predicts for inferior outcome in molecularly-defined subsets of AML, that is, NPM1-wildtype AML and molecular unfavorable CN-AML. As a single marker, DNMT3Amut only had a moderate effect on outcome. Disclosures: No relevant conflicts of interest to declare.

EZH2 Mutations Are Associated with Low Blast Percentage in Bone Marrow and −7/Del(7q) Karyotype in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2544-2544
Author(s):  
Xiuli Wang ◽  
Haiping Dai ◽  
Qian WANG ◽  
Qinrong Wang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Coding Region ◽  
Acute Myeloid

Abstract Abstract 2544 Somatic mutation of the EZH2 gene is seen in myelodisplastic syndrome, myelofibrosis, and chronic myelomonocytic leukemia patients. The prevalence and prognostic impact of somatic mutations of EZH2 in patients with acute myelogenous leukemia (AML) remains unknown. In this study, we sought to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo AML by PCR amplification of the entire coding region followed by direct bidirectional DNA sequencing. EZH2 mutations were identified in 13/714 (1.8%) of AML patients and occurred almost exclusively in males (11/13, P=0.033). In univariate analysis, the presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (P=0.0001) and −7/del(7q) (P=0.025). There was no difference in the incidence of mutations in 13 genes, including ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. Complete remission, event-free survival or overall survival was similar between AML patients with and without EZH2 mutation (p>0.05). These results demonstrated EZH2 mutation as a recurrent genetic abnormality associated with lower blast percentage in BM and −7/del(7q) in de novo acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7073-7073
Author(s):  
W. M. McHayleh ◽  
R. Redner ◽  
R. Sehgal ◽  
A. Raptis ◽  
M. Agha ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Duration ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Acute Myeloid

7073 Background: The goal of induction chemotherapy in acute myeloid leukemia (AML) is complete remission with restoration of normal bone marrow. If residual leukemia is present after the first course of induction therapy, patients receive a second course identical to the first or receive a non-cross resistant antileukemic regimen. Methods: In a retrospective study of adult patients with newly-diagnosed AML treated at the University of Pittsburgh Cancer Institute between December 2002 and May 2008, we evaluated the efficacy and toxicity of mitoxantrone (10 mg/m2/d) and etoposide (100 mg/m2/d), both administered intravenously within 5 days as second course therapy of patients not responding to first-course induction therapy with cytarabine and idarubicin. Univariate and multivariate associations between patient characteristics and complete response (CR) were assessed by logistic regression, with overall- and relapse-free survival estimated by Kaplan-Meier analysis. Results: 74 AML patients (mean age 56 years, range: 18–73 years) completed treatment with etoposide and mitoxantrone; 29 (39%) achieved CR. Lower CR rate was associated with unfavorable cytogenetic risk status at diagnosis and higher percent blasts prior to treatment with mitoxantrone and etoposide. Ten (14%) patients died due to infectious complications. No grade 3 or 4 hepatic toxicities were observed. One patient developed grade 3 cardiac toxicity. Median duration of neutrophil recovery following therapy in patients achieving CR was 29 days. Median overall survival was 9.0 months (95% CI 5.8–14.9 months). The 29 patients who achieved CR received postremission therapy: 16 of these eventually relapsed, while 4 others died without evidence of relapse. Median duration of relapse-free survival in these 29 patients was 11.0 months (95% CI: 9.0–19.3 months). Conclusions: Our study suggests that the combination of etoposide and mitoxantorne is an active and well-tolerated regimen as second-course therapy in newly diagnosed AML patients who have persistent leukemia after a first course of induction therapy with cytarabine and idarubicin. No significant financial relationships to disclose.

scholarly journals Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4422-4429 ◽  
Author(s):  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Poor Performance ◽  
Risk Groups ◽  
Complete Response ◽  
Intensive Chemotherapy ◽  
Acute Myeloid

Patients ≥ 70 years of age with acute myeloid leukemia (AML) have a poor prognosis. Recent studies suggested that intensive AML-type therapy is tolerated and may benefit most. We analyzed 446 patients ≥ 70 years of age with AML (≥ 20% blasts) treated with cytarabine-based intensive chemotherapy between 1990 and 2008 to identify risk groups for high induction (8-week) mortality. Excluding patients with favorable karyotypes, the overall complete response rate was 45%, 4-week mortality was 26%, and 8-week mortality was 36%. The median survival was 4.6 months, and the 1-year survival rate was 28%. Survival was similar among patients treated before 2000 and since 2000. A multivariate analysis of prognostic factors for 8-week mortality identified the following to be independently adverse: age ≥ 80 years, complex karyotypes, (≥ 3 abnormalities), poor performance (2-4 Eastern Cooperative Oncology Group), and elevated creatinine > 1.3 mg/dL. Patients with none (28%), 1 (40%), 2 (23%), or ≥ 3 factors (9%) had estimated 8-week mortality rates of 16%, 31%, 55%, and 71% respectively. The 8-week mortality model also predicted for differences in complete response and survival rates. In summary, the prognosis of most patients (72%) ≥ 70 years of age with AML is poor with intensive chemotherapy (8-week mortality ≥ 30%; median survival < 6 months).

Results of Acute Myeloid Leukemia Treated with Triple-Drug Regimen Based on HA as Induction Chemotherapy and Its Relationship with Karyotype.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4595-4595
Author(s):  
Jianxiang Wang ◽  
Yingchang Mi ◽  
Yangping Xue ◽  
Wenjuan Yu ◽  
Shougeng Bian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Risk Groups ◽  
Drug Regimen ◽  
Free Survival ◽  
Intermediate Group ◽  
Favorable Group ◽  
Acute Myeloid

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.

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