Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS

2010 ◽  
Vol 28 (18) ◽  
pp. 3028-3034 ◽  
Author(s):  
Arnaud Pigneux ◽  
Jean-Luc Harousseau ◽  
Francis Witz ◽  
Mathieu Sauvezie ◽  
Marie-Christine Bene ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Group I ◽  
Acute Myeloid

Purpose No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m2, days 1 through 5) and cytarabine (100 mg/m2, days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

Improved Outcome by Addition of Lomustine (CCNU) to Idarubicin and Cytarabine in Elderly Patients with De Novo Acute Myeloid Leukemia. A Report from the GOELAMS Group

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 761-761
Author(s):  
Arnaud Pigneux ◽  
Francis Witz ◽  
Mathieu Sauvezie ◽  
Marie-Christine Bene ◽  
Isabelle Luquet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Group I ◽  
Group Ii ◽  
Acute Myeloid

Abstract In elderly patients with acute myeloid leukemia (AML) treated intensively, no improvement has been shown in the last 20 years. We performed a retrospective study in 847 patients over 60 years old, prospectively enrolled in 3 trials conducted in France between 1995 and 2005, with the aim to investigate prognostic factors for complete remission (CR) achievement and survival. Induction therapy consisted in the association of Idarubicin 8mg/m2 d1-5 and Cytarabine 100mg/m2 d1-7 (Group I, 339 patients) or the same drugs with the addition of lomustine (10mg\m2 orally at day 1)(Group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course with intermediate dose cytarabine. The patients’ characteristics were similar between the two groups concerning sex, WBC count, ECOG, and cytogenetics, yet patients were older in Group II versus Group I (55% versus 45% over 69 years of age, p<0.0001).The CR rate was significantly higher for patients in Group II compared to Group I (67 % vs 57%, p= 0.002). The toxic death rate was not different between groups. In multivariate analysis, three good prognostic factors emerged for achieving complete remission: good or intermediate cytogenetics (p<0.0001), ECOG < 2 (p<0.0001), and adjunction of lomustine to induction chemotherapy (p=0.002). The median overall-survival was significantly improved for patients treated with lomustine (12.7± 2.2 months vs 8.7± 2.7 months, p=0.004). In multivariate analysis, five prognostic factors affected positively overall survival: adjunction of lomustine to induction chemotherapy (p < 0.0001), age < 69 years (p =0.001), ECOG < 2 (p =0.001), FAB other than AML0,6 or 7 (p = 0.004) and good or intermediate cytogenetics(p = 0.007). The median event-freesurvival was also improved for patients treated with lomustine (10.7± 2.2 months vs 7± 2.7 months, p=0.002). Event-free-survival was affected by the same prognostic factors as overall survival. We conclude that lomustine might be added in standard induction therapy as it allowed to obtain both better CR rate and survival in this retrospective study.

Elderly Patients with Acute Myeloid Leukemia Are Not All the Same: Results of the Prospective DSIL AML96 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1840-1840
Author(s):  
Markus Andreas Schaich ◽  
Walter E. Aulitzky ◽  
Heinrich Bodenstein ◽  
Martin Bornhaeuser ◽  
Thomas Illmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
High Risk ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Severe Toxicity ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract The majority of patients with acute myeloid leukemia (AML) are older than 60 years at diagnosis. However, treatment results for these elderly patients are still unsatisfactory. This is thought to be due to a more aggressive disease, preexisting co-morbidities or a decreased tolerance for intensive treatment approaches. As for younger patients there is growing evidence that elderly AML patients may be divided into prognostic subgroups. So far data on prognostic factors in this group of patients are still sketchy. Between February 1996 and March 2005 a total of 827 elderly AML patients with a median age of 67 (61–87) years were treated within the prospective AML96 trial of the German Study Initiative Leukemia (DSIL). 643 patients had de novo and 184 patients secondary disease. All patients were scheduled to receive a double induction therapy with Daunorubicin and Ara-C (DA3+7). The consolidation therapy consisted of one course of m-Amsacrine and intermediate-dose (10g/m2) Ara-C. 265 (32%) patients reached CR criteria after double induction therapy. Forty-two patients (5%) had only a PR, 307(37%) displayed refractory disease, 126(15%) died during induction therapy and 77(10%) received only one course of induction therapy due to severe toxicity. Out of the 265 patients in CR 120 (45%) patients received the consolidation course. The strongest independent prognostic factors for achieving a CR were less than 10% blasts in the day 15 bone marrow, the presence of a NPM mutation or a low-risk karyotype (p&lt;0.0001 each). The 3-year overall (OS) and relapse-free survival (RFS) rates were 18% for all patients and 17% for all patients in CR, respectively. In the multivariate analysis the strongest prognostic factors for survival were age, LDH and cytogenetics (p&lt;0.0001 each). Using these three parameters a prognostic model for survival was established. Patients older than 70 years with intermediate- or high-risk cytogenetics and a high LDH level at diagnosis (n=213) had a 3-year OS of only 9%, whereas patients with low-risk cytogenetics or patients with intermediate-risk cytogenetics, younger than 70 years and a low LDH level (n=237) had a 3-year OS of 32%. All other patients (n=377) had an intermediate 3-year OS of 15% (p&lt;0.0001). In conclusion, elderly AML patients can be stratified into prognostic groups. AML patients older than 70 years with high LDH levels and intermediate- or high-risk cytogenetics at diagnosis do not profit from conventional chemotherapy.

Clinico-Biological Characteristics and Prognosis of Non-M3 Acute Myeloid Leukemia with High Percentage of Myeloperoxisase Positive Blasts. Single Center Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4462-4462
Author(s):  
Pau Montesinos ◽  
Lorenzo Algarra ◽  
Jaime Sanz ◽  
Mari Luz Perez ◽  
Leonor Senent ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Favourable Outcome ◽  
Biological Characteristics ◽  
Prognostic Impact ◽  
Acute Myeloid

Abstract Introduction: It has been suggested that acute myeloid leukemia (AML) showing mature phenotype is associated with favourable outcome. In a study recently published by JALSG, myeloperoxidase (MPO) positivity in over 50% of blasts had favourable prognostic impact, independent from karyotype, on achieving complete remission (CR), overall survival (OS) and disease free survival (DFS). No other studies have established the independent prognostic value of MPO expression. Objectives: Analyze the clinico-biological characteristics of AML with high percentage of MPO+ blasts and its impact on CR, OS and DFS. Material and methods: Between 1986 and 2005, 418 adult patients (median 53 years, range 15–80) were diagnosed with de novo non-APL AML and evaluated for percentage of MPO+ blasts. All patients received intensive chemotherapy. Diagnosis was made by optic microscopy of bone marrow (BM) aspirates stained with May-Grumwald giemsa, MPO, butyrate esterase and or non specific esterase. Cytogenetic and immunophenotype analysis was evaluated in 66% and in 76% of the cases respectively. Results: 118 patients (28%) showed a percentage of MPO+ blasts >75%. AML with MPO+ blasts >75% was associated with M1-M2-M4 subtypes, leucocytes >50×109/L, blasts in BM >70% and HLA-DR negativity (p<0.01). It was also significantly associated with favourable karyotype (11% vs 3% favourable, 52% vs 48% intermediate and 3% vs 15% unfavourable). Patients with AML and MPO+ blasts >75% obtained higher CR rate (71% vs 55%), due to less resistant disease (9% vs 22%, p<0.01). In multivariate analysis favourable karyotype, leukocytes <50×109/L and age <60 were favourable prognostic factors for CR. Median OS and DFS was higher in patients with AML and MPO+ blasts >75% (15 vs 7 months, p<0.001, y 41 vs 12 months, p<0.001, respectively). ). In multivariate analysis, favourable karyotype, leukocytes <50×109/L, age <60 years and MPO+ >50% were favourable prognostic factors for OS; and age <60 and MPO+ >75% were the only independent factors for DFS. Median DFS was higher in patients with AML and MPO+ blasts >75% in the intermediate cytogenetic risk group (59 vs 13 months, p=0.015), age <60 (109 vs 15 months, p=0.003), age >60 (13 vs 7 months, p=0.03), autologous stem cell transplantation (100 vs 9 months, p=0.04) and chemotherapy alone (16 vs 8 months, p=0.003). Conclusion: In our series, patients with AML and MPO+ blasts >75% show less chemoresistant disease and a longer remission duration, the latter independently from the karyotype. This biological characteristic could be useful in designing therapeutic strategies in patients that lack other prognostic markers.

Incidence and Prognostic Factors for Infectious and Hemorrhagic Death in Patients with Acute Myeloid Leukemia: A Single-Centre Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4300-4300 ◽  
Author(s):  
Pau Montesinos ◽  
Guillermo Martin ◽  
Ninotchka Mendoza ◽  
Jesus Martinez ◽  
Federico Moscardo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
High Dose ◽  
Induction Failure ◽  
Acute Myeloid

Abstract INTRODUCTION: Death is as a common cause of remission induction failure in patients with acute myeloid leukemia (AML), mainly due to hemorrhage and infection. The relative incidence and chronology of each of these categories of induction failure, as well as their prognostic factors, have been investigated critically and in detail in rare studies only. OBJECTIVES: We report the incidence, chronology, and prognostic factors for induction death, analyzing separately hemorrhagic and infectious death, in a large series of 946 patients with AML who received induction therapy in a single institution over the last 30 years. PATIENTS AND METHODS: Adult patients were consecutively diagnosed of AML and started first induction chemotherapy in our institution. AML was classified according to the FAB criteria. Induction therapy consisted of the classic combination of cytarabine and anthracyclines (with or without a third agent) in 50% of patients, cytarabine plus adriamicine and thioguanine or vincristine in 17%, ATRA with chemotherapy in 9%, monochemotherapy with anthracycline in 7%, high dose cytarabine in 7%, and other regimens in 10%. Causes of induction death include the following categories: Infection, when death was due to a clinical, radiological or microbiologically documented infection, Hemorrhage, when a major bleeding occured in a vital organ (central nervous system, lungs). Gastrointestinal hemorrhage required massive melena or hematemesis accompanied by fall in blood pressure, and Other, i.e., any other cause not classified as infection or hemorrhage. RESULTS: From 1977 to 2007, 946 consecutive patients with diagnosis of AML received induction chemotherapy, 24% in the period 1 (1977–1986), 28% in the period 2 (1987–1993), 28% in the period 3 (1994–2000), and 20% in the period 4 (2001–2007). Median age was 55 years (range 13–83 years). One hundred and sixty-seven patients (18%) had antecedents of myelodysplastic/myeloprolipherative disease (10%) or other neoplasia (8%). Two hundred and thirty-seven patients (25%) died during induction therapy, 13% due to infection, 7% due to hemorrhage, 2% due to hemorrhage and infection, and 3% due to other causes. The induction mortality rates decreased gradually over the 4 periods (31% vs 24% vs 18% vs 18%), due to reduction of both hemorrhagic and non-hemorrhagic deaths. Overall, 42% of hemorrhagic deaths occurred within the first 10 days of induction therapy, whereas 86% of infectious deaths occurred after 10 days. In multivariate analysis, the following characteristics had an unfavorable impact on overall induction mortality: age >60 years, WBC >50x109/L, Quick index <65%, ECOG >1, and albumin serum levels <3.5mg/dL. Multivariate analysis identified the following factors predicting for infectious mortality: albumin <3.5mg/dL, age >50 years, AML secondary to neoplasia, ECOG >1, and fever at presentation. The following factors were associated with hemorrhagic mortality: WBC >50x109/L, FAB-M3, age >60 years, de novo AML, and ECOG >1. CONCLUSIONS: The main causes of induction death in AML patients, infection and hemorrhage, shows a different chronologic pattern and can be separately predicted by their own specific prognostic factors.

Comparison of Outcome and Prognosis of 248 Elderly Patients with Acute Myeloid Leukemia Treated with Standard-Dose or Low-Intensity Induction Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2540-2540
Author(s):  
Jianda Hu ◽  
Yi Chen ◽  
Xiaoyun Zheng ◽  
Zhihong Zheng ◽  
Ting Yang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Standard Dose ◽  
Performance Status ◽  
Low Intensity ◽  
Induction Cycle ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a disease of older adults, with a median onset age at about 65-70 years. The treatment outcome of AML appears to be poorer with the age increasing, in part due to the poor performance status, concomitant end-organ dysfunction, higher incidence of unfavorable cytogenetic findings, frequent involvement of a more immature leukemic precursor clone, multidrug resistance mediated by MDR1/P-glycoprotein, and the presence of antecedent hematopoietic disorders. Treatment of elderly patients with AML remains highly challenging and controversial. The overall survival rates at 5-year of ≥ 60 years old AML patients are still less than 20% by now. At present, standard-dose induction chemotherapy using a cytarabine plus idarubicin(IA regimen) or daunorubicin (DA regimen) was considered by most to be the most effective upfront AML induction therapy. However, there are still quite a number of elderly patients could not tolerate because of poor performance status and complications. Therefore, low-intensity chemotherapy, including CAG regimen, which combine low-dose cytarabine, aclacinomycin and granulocyte colony-stimulating factor(G-CSF), was used for those were not appropriate for receiving standard-dose chemotherapy. Here we retrospectively analyzed the outcome and prognosis of elderly patients with AML treated with standard-dose or low-intensity induction therapy. 248 elderly patients with acute myeloid leukemia(AML) who received standard-dose or low-intensity induction therapy were enrolled in this retrospective clinical study, 186 patients in standard-dose group with 144 in IA and 42 in DA, 62 cases in low-intensityCAG group. The maininclusion criteria included age ≥ 60 years old, ECOG performance status ≤ 2, without severe complication of heart, liver, kidney or other important organ. The patients received standard-dose or low-intensity induction regimen according to their performance status and patient preference. 144 patients received IA regimen(idarubicin 10mg/m2/d ,d1-3; cytarabine 100mg/m2, q12h, d1-5 or 7), 42 patients received DA regimen(daunorubicin 60mg/m2/d, d1-3; cytarabine 100mg/m2 q12h, d1-5 or 7), and 62 patients received CAG regimen (cytarabine 10mg/m2 q12h, d1-14; aclacinomycin 20mg qd, d1-4; G-CSF 200ug/m2 qd, d0-14, or until bone marrow recover). The median survival time was 9.2 months. 1-year , 3-year and 5-year overall survival(OS) were 42.2%, 18.9% and 13.5%, respectively. After first induction cycle, complete remission(CR) rate was 49.3% in IA group, 35.7% in DA group and 32.3% in CAG group (P = 0.046). The median OS for IA, DA and CAG group were 10.0 months, 9.7months and 7.5 months, respectively. The early mortality of induction therapy and recurrence rate of three regimens showed no difference. IA could improve the long term survival compared to CAG and DA, with 3-year OS: 23.5%,15.9% and 8.3%, respectively; 5-year OS: 19.4%, 6.3%, and 0, respectively (P<0.01). The 67.0% patients relapsed within 24 months, with median relapse time of 8.4 months, 14.6 months and 8.3 months for IA, DA and CAG regimen, respectively. Moreover, Kaplan-Meier analysis showed that 7 parameters were adverse prognostic factors for OS, including age ≥ 70 years old, poor ECOG performance status, unfavorable cytogenetics, non-remission after first induction cycle, white blood cell (WBC) counts ≥ 50×10^9/L, percentage of bone marrow (BM) blast ≥ 80% and higher lactic dehydrogenase (LDH) . Multivariable analysis identified non-remission after first induction cycle (HR = 6.141, 95%CI: 3.585-10.52, P = 0.000) and LDH ≥ 490 IU/L(HR = 1.001, 95%CI: 1.000-1.001, P = 0.000) as independent significantly prognostic factors for OS. In conclusion, Our present data showed that standard-dose IA regimen could improve CR rate and prolong the survival time compared to low-intensity CAG regimen, and CAG regimen still has a certain therapeutic effect for those unfit for intensive chemotherapy. Recurrence is still a serious problem for those who do not receive Allo-HSCT for consolidation after CR. All prognostic factors should be considered before induction therapy to make sure the patients receive the best individualized treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia

2005 ◽  
Vol 16 (8) ◽  
pp. 1366-1373 ◽  
Author(s):  
C.-C. Chen ◽  
C.-F. Yang ◽  
M.-H. Yang ◽  
K.-D. Lee ◽  
W.-K. Kwang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Acute Myeloid

scholarly journals Immunohistochemical Expression of CD123 Is Associated with an Inferior Clinical Outcome in Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2887-2887
Author(s):  
Nana Arai ◽  
Bungo Saito ◽  
Maasa Abe ◽  
Megumi Watanuki ◽  
So Murai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multivariate Analysis ◽  
Clinical Outcome ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
P53 Expression ◽  
De Novo Aml ◽  
Induction Failure ◽  
Acute Myeloid

Abstract Background: The aberrant expression of the interleukin-3 receptor (IL3RA or CD123) alpha chain is frequently observed in a subset of leukemic disorders, including acute myeloid leukemia (AML), particularly in leukemia stem cells. Using flow cytometric (FCM) analysis, studies have shown that increased CD123 expression is associated with a poor prognosis of AML. Although FCM is a sensitive technique, the analysis may be limited in a clinical setting because live leukemia cells are required. Immunohistochemistry (IHC) is a more useful alternative compared with FCM because it can be tested long after specimens are collected; however, it is less sensitive. Here we evaluated the impact of blast CD123 expression via IHC analysis for the prognosis of AML. Patients and methods: This study was performed as a retrospective analysis of 70 patients who were diagnosed with de novo AML (M0-M5, n = 48) and AML with myelodysplasia-related changes (MRC) (n = 22) at our hospital from February 2008 to September 2015. The median age at diagnosis was 64.5 years (range: 21-93 years). The median follow-up period was 498 days (range: 2-3052 days). Morphological findings were obtained using HE stains of 3-µm sections. Formalin-fixed, paraffin-embedded specimens were used for immunohistochemical analysis. We analyzed the relationships between the patients' clinical outcome and CD123, p53, CD34, CD71, CD56, and c-kit expressions. [(CD123, CD34, CD71, CD56, and c-kit immunostained slides were defined as positive if >10% of the blast cells had a moderate to strong membranous staining. p53 was evaluated as positive when more than 5% of the cells were positively stained. For each case, the following data were obtained: patient age (>60 years or <60 years), sex, karyotype (good, intermediate, or poor), SCT (undergone or not), 1st induction (failure or complete remission (CR), and overall survival (OS)]. Results: Of the 70 cases, percentages of the positive immunohistochemical study dates were as follows: CD123: 25.7%; p53: 30%; CD34: 52.8%; CD71: 46.3%; CD56: 25.7%; and c-kit: 77.1%. There were 48 cases with de novo AML: CD123: 29.1%; p53: 75%; CD34: 52%; CD71: 37.5%; CD56: 27%; and c-kit: 79.1%. Moreover, there were 22 cases with MRC: CD123: 18.1%; p53: 31.8%; CD34: 54.5%; CD71: 66.6%; CD56: 22.7%; and c-kit: 72.7%. CD71 is highly expressed in MRC than de novo AML (P = 0.036). Among all patients, the CR rate following first induction therapy was 62.3%. Age (≥60 years), high p53 expression, disease (MRC), and poor karyotype were associated with induction failure (P = 0.011, P = 0.002, P <0.001, and P = 0.008, respectively). Among patients with de novo AML, only elevated CD123 expression was associated with the failure to obtain a CR following the first remission induction chemotherapy (P = 0.044). In contrast, among patients with MRC, CD123 expression was not associated with any clinical data or the CR rate. The 2-year OS rates were 45.9%. Age (≥60), high p53 expression, MRC, poor karyotype were significantly associated with poor OS (P = 0.003, P = 0.036, P <0.001, and P = 0.002, respectively). In Multivariate analysis, age (≥60 years), MRC, poor karyotype are significantly associated with poor OS (P = 0.028, P = 0.001, and P = 0.014, respectively). Among de novo AML patients, CD123 expression, p53 expression, and induction failure were independently associated with poor OS (P = 0.036, 0.003 and P < 0.001, respectively), and increased p53 expression and induction failure was associated with poor OS in the multivariate analysis (P = 0.001 and P = 0.002). Among patients with MRC, only induction failure was associated with the OS (P = 0.026). Conclusion: This is the first study to demonstrate that CD123 expression using IHC is associated with poor a CR rate and OS in de novo AML patients; however, this association was not observed in MRC patients. Our results suggest that CD123 expression may predict the refractory to induction therapy and poor OS in de novo AML. Moreover, these results support previous reports using FCM. Therefore, CD123 expression may become one of the important factors used to characterize leukemia blasts and predict the prognosis of AML. In addition, novel therapy with antibodies targeting CD123 is currently under development. Therefore, we suggest that an analysis of CD123 expression using IHC is a clinically important assessment for de novo AML patients at the time of diagnosis. Disclosures No relevant conflicts of interest to declare.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

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 ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

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.

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