Incidence and Risk Factors for Central Nervous System Relapse in Adult Patients with Acute Myeloid Leukemia: A Single Center Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4579-4579
Author(s):  
Pau Montesinos ◽  
Guillermo Martin ◽  
Mari-luz Perez-sirvent ◽  
Jaime Sanz ◽  
Ignacio Lorenzo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Intrathecal Chemotherapy ◽  
Adult Patients ◽  
Cns Relapse ◽  
First Relapse ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Introduction: There is scarce information concerning incidence and risk factors for central nervous system (CNS) relapse in adult patients with acute myeloid leukemia (AML). In acute lymphoblastic leukemia CNS relapse occurs in up to 30% of patients without prophylactic intrathecal chemotherapy (ITC). This has lead to establish its prophylactic use during induction and post-remission phase. Due to the lack of information about incidence of CNS relapse in adult patients with AML, the usefulness of ITC prophylaxis is not clear. Objectives: Analyze incidence and risk factors for CNS relapse in a large cohort of adult patients with newly diagnosed AML. Material y methods: Between 1976 y 2005, 747 adult patients (median 54 years, range 16–81) were diagnosed of de novo AML in our institution. All of them received induction with intensive chemotherapy. Prophylactic ITC was not administered, and cerebrospinal fluid was analyzed only if CNS infiltration was suspected. We analyzed the incidence and risk factors for CNS relapse in patients who reached a complete remission. To calculate the Kaplan-Meier estimates of event-free survival (EFS) we considered as an event the first relapse in CNS, censoring patients at the moment of death or at first relapse in a site different than CNS. Results: 432 patients (58%) obtained complete remission. Between 1976 and 1989 (period 1) 12 of 136 patients (9%) were submitted to autologous or allogeneic stem-cell transplantation (SCT), whereas 129 of 296 (44%) received SCT between 1990 and 2005 (period 2). Overall, 8 of 432 patients (2%) had a CNS relapse, 3 isolated in CNS and 5 in bone marrow plus CNS. Of them, only 1 presented CNS infiltration at diagnosis. In univariate analysis, CNS relapse was associated with high LDH (3% vs 0%, p=0.06), lisozyme >30 (8% vs 1%, p=0.06), FAB M4–M5 (5% vs 1%, p=0.04) and period 1 (5% vs 0.3%, p<0.01). The median follow-up of the cohort was 85 months. CNS relapses occurred at a median of 10 months after complete remission (range, 3 to 84 months). The EFS at 10 years was 95%, and it was lower in patients with elevated LDH (91% vs 100%, p=0.02), FAB M4–M5 (88% vs 97%, p<0.01), leukocytes >10 ×109/L (92% vs 98%, p=0.07), no SCT (92% vs 100%, p<0.01), and period 1 (80% vs 99%, p<0.01). In multivariate analysis, AML M4–M5 remained as the only independent prognostic factor for EFS (HR 6.4, p=0.01). Only 1 of 8 patients with CNS relapse is alive (AML M3, 11 years after a second complete remission). Median survival after CNS relapse was 168 days (range, 16 to 3821 days). Conclusion: In adults with de novo AML CNS relapse is an infrequent event. Intensification of post-remission therapy, especially with SCT, during the last decades may have contributed to reduce its incidence. Therefore, administration of prophylactic intrathecal chemotherapy should not be recommended, even in patients with high risk of CNS relapse, such as monocytic AML.

The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2137-2145 ◽  
Author(s):  
Sabine Kayser ◽  
Konstanze Döhner ◽  
Jürgen Krauter ◽  
Claus-Henning Köhne ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Negative Impact ◽  
Primary Malignancy ◽  
De Novo Aml ◽  
The Impact ◽  
Acute Myeloid

Abstract To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

scholarly journals Prognostic Impact of the Interaction between DNMT3A mutation and Internal Tandem Duplication of the FLT3 Gene (FLT3-ITD) in Patients with De Novo Mutated NPM1 (NPM1mut) acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1492-1492
Author(s):  
Guadalupe Oñate ◽  
Ana Garrido ◽  
Jordi Esteve ◽  
Rosa Coll ◽  
Montserrat Arnan Sangerman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Mutational Status ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Introduction The association of NPM1mut and FLT3-ITD in de novo acute myeloid leukemia (AML) with intermediate-risk cytogenetics has different prognostic impact depending on the FLT3 allelic burden. Previous studies published by our cooperative group showed that patients with de novo AML of intermediate-risk cytogenetics with NPM1mut and FLT3-ITD low ratio (<0.5, FLT3low) at diagnosis presented an overall survival and relapse rate similar to those with NPM1mut and FLT3wt. Therefore, in the CETLAM-2012 protocol, patients with FLT3low NPM1mut AML are not considered for allogenic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1). Recent studies suggest that the co-occurrence of DNMT3A mutation in FLT3-ITD NPM1mut AML patients confers a worse prognosis regardless of FLT3-ITD ratio. We analysed our data to determine whether these findings were confirmed in our cohort, specifically in the low FLT3-ITD ratio patients, since this could have therapeutic implications. Methods and patients A total of 163 patients with de novo AML, intermediate-risk cytogenetics and NPM1mut were analysed (median age 53 years (18-72); male:female 72:91 (0.79)). Eighty patients (49%) harboured an FLT3-ITD, with a high allelic ratio in 42 of 76 patients with available ITD/wt ratio (55%). They were included in the AML-2003 (n=49) and AML-2012 (n=114) CETLAM protocols. Proportion of patients undergoing alloHSCT in CR1 is detailed in table 1. Bone marrow samples from diagnosis were studied for DNMT3A mutations as previously described. The definition of complete remission (CR), overall survival (OS), leukemia-free survival (LFS) and risk of relapse (RR) followed recommended ELN criteria. The Kaplan-Meier method was used to estimate the distribution of LFS and OS, for RR cumulative incidence was used. Results Out of the 163 patients with AML of intermediate risk cytogenetics and NPM1mut, 78 presented DNMT3A mutations (48%). Of these, 62 (79%) presented mutations in codon R882 or corresponded to DNA insertions/deletions while 16 (21%) harboured missense mutations. Presence of DNMT3A mutation did not associate with FLT3-ITD (ITD/85 DNMT3Awt vs ITD/78 DNMT3Amut, p=0.394). In the entire cohort, 5-year OS, LFS and RR were 58±4.5%, 59±4.6% and 27±13.9%. FLT3-ITD ratio confirmed its prognostic impact when analysing FLT3wt (n=83) vs FLT3low (n=34) vs FLT3high (n=42) patients (5-year OS of 68±6% vs 62±8.7% vs 37±8.6%; p=0.002; and 5-year RR of 18±9.4% vs 27±16.1% vs 41±23.2%; p=0.023). On the contrary, DNMT3Amut did not exert any effect on overall outcome (5-yr OS DNMT3Awt vs DNMT3Amut 61±6.2% vs 55±6.2%; p=0.234) When DNTM3A mutational status was considered, the impact of FLT3-ITD on outcome was mitigated in wild-type DNMT3A population. Thus, we found that DNMT3Awt patients presented no statistical differences in OS according to FLT3 mutational status or ratio: FLT3wt (n=46) vs FLT3-ITD (n=39) was 67±8.5% vs 57±8.2%; p=0.122, whereas FLT3wt (n=46) vs FLT3low (n=18) vs. FLT3high (n=19) was 67±8.5% vs. 66±11.5% vs 46±11.8%; p=0.088 (image 1A).This was also seen in relation to LFS and RR according to FLT3 ratio: 5-yr LFS of FLT3wt vs FLT3low vs FLT3high was 72±7.9% vs 61±12.6% vs 51±13.4%; p=0.244 and 5-year RR of the same groups: 19±8.8% vs 26±12.5% vs 27±21.9%; p=0.724 (image 2A). In the DNMT3Amut group, patients with FLT3-ITD (n=41) presented shorter OS than those with FLT3wt (n=37) with an OS of 37±10.7% vs 69±7.8%; p=0.028. When FLT3 ratio was considered, FLT3wt (n=37) vs FLT3low (n=16) vs FLT3high (n=23) showed an OS of 69±7.8% vs. 58±13.2% vs 27±13.1%; p=0.038 (image 1B). Similar results were seen in LFS according to FLT3 ratio (FLT3wt (n=29) vs FLT3low (n=16) vs FLT3high (n=20) 71±8.6% vs 53±12.9% vs 18±13.8%; p=0.012). Finally, we observed significant differences in the 5-year RR when considering DNMT3Amut patients in relation to FLT3 ratio (FLT3wt vs FLT3low vs FLT3high 18±10.6% vs 27±20% vs 54±28.8%; p=0.021)(image 2B). Conclusions In this study, patients with NPM1mut and FLT3-ITDlow presented a similar outcome to patients with NPM1mut and FLT3wt regardless of DNMT3A mutational status. These results support the modification of alloHCST policy in CR1 in CETLAM-2012, which do not consider alloHSCT for patients with FLT3low. On the other hand, concurrence of DNMT3A mutation may have an added negative effect in patients with NPM1mut and FLT3-ITDhigh, which should be further confirmed in larger studies. Disclosures No relevant conflicts of interest to declare.

A Phase II Study of Twice Daily Cytarabine and Fludarabine and Gentuzumab Ozogamycin (GO) In Patients (pts) with Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2188-2188
Author(s):  
Elias Jabbour ◽  
Guillermo Garcia-Manero ◽  
Hady Antoine Ghanem ◽  
Farhad Ravandi ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Phase Ii ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Phase Ii Study ◽  
Platelet Recovery ◽  
First Relapse ◽  
De Novo Aml ◽  
To Receive

Abstract Abstract 2188 Background: Treatment options for pts with refractory/relapsed (R/R) AML are limited. High dose cytarabine (A) containing regimens are still considered standard options for pts with AML relapsing after a first complete remission (CR) lasting more than 12 months. The combination of A with fludarabine (F) was found to be superior to A alone in this setting, particularly when administered twice daily (BID). In addition, gemtuzumab ozogamicin (GO) has been shown to be active in combination or as single agent in pts with R/R AML. Therefore, we conducted a phase II study assessing the efficacy and safety of BID FA-GO. Patients and Methods: Pts with R/R AML, de novo AML patients unfit for other medical therapies, intermediate-2 and high-risk MDS, and chronic myeloid leukemia in myeloid blast crisis (CML-BC), with a performance status (PS) of 3 or less, as well as normal organ functions were eligible. Pts were scheduled to receive F 15 mg/m2 IV q12 hrs day 1 to 5 as well as A at the dose of 0.5 g/m2 IV over 2 hrs q12 hrs day 1 to 5. GO was administered at the dose of 3 mg/m2 IV on day 1. Treatment course was shortened to 4 days in pts older than 65 years and to 3 days in pts with a PS of 3. Courses were repeated every 4 to 6 weeks for a maximum of 7 courses. Pts with CML were allowed to receive concomitant tyrosine kinase inhibitors. Results: Sixty-five evaluable pts were enrolled: 6 (9%) with de novo AML, 5 (8%) with AML in first relapse with a duration of 1st CR (CRD1) of ≥12 months, 21 (32%) with AML with CRD1 <12 months, 24 (37%) with AML in second relapse and beyond, 3 (5%) with MDS, and 6 (9%) with CML-BC. Median age was 60 years (range, 19 to 80); 58 pts (89%) had a PS ≥1. Cytogenetic analyses were abnormal in 63 % including chromosomes 5 and 7 abnormalities in 17%. The overall response (OR) rate was 31% including CR in 17 pts (26%) and CR without platelet recovery (CRp) in 3 (5%). The overall 4-week mortality rate was 8%. The OR rates for pts with de novo AML, relapsed AML with CRD1 ≥12 months, relapsed AML with CRD1< 12 months, and R/R AML beyond first salvage (S) were 43%, 60%, 35%, and 19%, respectively. The CR rates were 29%, 60%, 27%, and 19%, respectively. The 4-week mortality rates were 19% for pts with R/R AML beyond the first salvage and 0% for the rest (Table1). With a median follow-up of 8 months (range, 1 to 27), the 16-week event-free survival (EFS), overall survival (OS), and complete remission duration (CRD) rates were 25%, 61%, and 89%, respectively. The median EFS and OS for the responding pts were 27 weeks (4-31 weeks). When compared to historical match cohort pts treated at our institution, BID FA-GO was better, with an ORR rate of 60 % in pts with AML in first relapse with CRD1 ≥12 months compared to an expected rate of 50%, 19% in pts with relapsed AML with CRD1< 12 months compared to 11%, and 35% in pts with AML beyond the first salvage compared to 7% (Table 2). The treatment was well tolerated with only 3% of the pts experiencing grade 3 and 4 toxicities including mainly skin rash. The main toxicities were of gastro-intestinal origin and all were of grade 1 and 2. There was no case of veno-occlusive disease reported. Conclusion: BID FA-GO appears to be active with an ORR of 31% in heavily pre- treated population. This combination appears to be safe as well with a low rate of 4-week-mortality of 5%. Ongoing studies are exploring the role of the new generation of nucleoside analogues in this setting. Disclosures: Cortes: Pfizer: Consultancy, Research Funding.

Decitabine and Sorafenib Therapy in Patients with FLT3-ITD Mutant Acute Myeloid Leukemia Is Associated with High Response Rates—a Single Institute Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5284-5284 ◽  
Author(s):  
Monica Reddy Muppidi ◽  
Elizabeth A. Griffiths ◽  
James E. Thompson ◽  
Laurie A Ford ◽  
Craig W Freyer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Case Series ◽  
De Novo Aml ◽  
Dna Hypomethylating Agent ◽  
Acute Myeloid

Abstract Introduction: Patients with acute myeloid leukemia (AML) characterized by FMS-like tyrosine kinase-3 (FLT-3) internal tandem duplication (ITD) mutations have poor outcomes, especially in the relapsed setting. Although small molecule inhibitors of FLT-3 have been explored for these patients, many inhibitors have demonstrated limited single-agent efficacy with short response durations. Sorafenib, a multi-kinase inhibitor with activity against FLT-3, has previously been evaluated alone and in combination with induction chemotherapy or azacytidine in AML patients. Here we describe our experience with the combination of the DNA hypomethylating agent, decitabine (D), and sorafenib (S) for the treatment of FLT-3 ITD mutant AML. Methods: We retrospectively reviewed records of patients with FLT-3 ITD mutant AML who were treated off protocol with decitabine and sorafenib from 2011-present. Descriptive statistics, treatment response, and overall survival were recorded. Results: A total of six patients were identified. Mean age was 56 (range 34-70) years. Two-thirds (4/6) were female. All patients were confirmed to have recurrence of de novo AML characterized by FLT-3 ITD mutations prior to therapy. Patients received at least 1-2 cycles of concurrent decitabine 20 mg/m2 for 10 days and sorafenib 200-400 mg twice a day for 28 days. Five patients had relapsed/refractory AML (RR-AML) following 1-3 prior therapies. One patient had de novo AML in complete remission with incomplete count recovery (CRi) and received DS as consolidation. The overall response rate was 83%. Eighty percent (4/5) of patients with RR-AML attained CRi. One patient receiving DS consolidation attained complete remission (CR). Two patients received subsequent allogeneic stem cell transplantation with one individual still alive after 348 days. FLT3 ITD allelic ratio (available on 3 patients) decreased after DS therapy and correlated with CRi. Median overall survival was 111 days (range 59-348) from the initiation of DS to death from any cause or last known follow-up. Two patients developed treatment-related neutropenic fever/sepsis and elevated liver enzymes, respectively, which did not require dose adjustment. One patient developed heart failure of uncertain etiology. Conclusions: In this single institute case series, we demonstrated that the combination of decitabine (10 days) and sorafenib was well tolerated, resulted in high CR/CRi rates (80%), and prolonged overall survival in patients with heavily pretreated relapsed/refractory FLT-3 ITD mutant AML. Further investigation of this regimen in clinical trials is warranted. Table 1: Case series Patient Age(years) Sex No. of Prior therapies PriorAlloSCT * Blasts Prior to DS (%) No. of DSCycles Responseto therapy Overall survival (Days) 1 54 Female 3 N BM 70% 1 CRi 141 2 70 Female 1 N PB 53% 2 CRi 82 3 64 Male 1 N BM 68% 2 CRi 62 4 60 Male 1 N BM 2% 1 CR 198 5 34 Female 3 Y PB 48% 1 NR 348 6 58 Female 3 Y NA 2 CRi 59 Figure 1 Figure 1. *Allogeneic stem cell transplantation Disclosures Off Label Use: We are going to discuss the use of decitabine and sorafenib combination in relapsed/refractory FLT3 mutant AML. Decitabine is a DNA hypomethylating agent and sorafenib is a multikinase inhibitor, both of which have been evaluated individually in AML patients..

Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3903-3910 ◽  
Author(s):  
Jan Braess ◽  
Karsten Spiekermann ◽  
Peter Staib ◽  
Andreas Grüneisen ◽  
Bernhard Wörmann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Early Death ◽  
High Dose ◽  
Kaplan Meier ◽  
De Novo Aml ◽  
Dose Dense ◽  
Acute Myeloid

AbstractDose density during early induction has been demonstrated to be one of the prime determinants for treatment efficacy in acute myeloid leukemia (AML). The German AML Cooperative Group has therefore piloted a dose-dense induction regimen sequential high-dose AraC and mitoxantrone followed by pegfilgrastim (S-HAM) in which 2 induction cycles are applied over 11 to 12 days instead of 25 to 29 days as used in conventional double induction, thereby increasing dose density 2-fold. Of 172 de novo AML patients (excluding acute promyelocytic leukemia), 61% reached a complete remission, 22% a complete remission with incomplete peripheral recovery, 7% had persistent leukemia, 10% died (early death) resulting in an overall response rate of 83%. Kaplan-Meier estimated survival at 2 years was 61% for the whole group (patients with unfavorable karyotypes, 38%; patients with favorable karyotypes, 69%; patients with intermediate karyotypes, 75%) after S-HAM treatment. Importantly, the compression of the 2 induction cycles into the first 11 to 12 days of treatment was beneficial for normal hematopoiesis as demonstrated by a significantly shortened duration of critical neutropenia of 31 days compared with 46 days after conventionally timed double induction. (European Leukemia Trial Registry LN_AMLINT_2004_230.)

Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study

2015 ◽  
Vol 33 (31) ◽  
pp. 3641-3649 ◽  
Author(s):  
Lene Sofie Granfeldt Østgård ◽  
Bruno C. Medeiros ◽  
Henrik Sengeløv ◽  
Mette Nørgaard ◽  
Mette Klarskov Andersen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Intensive Therapy ◽  
Risk Groups ◽  
Population Based ◽  
National Population ◽  
De Novo Aml ◽  
Acute Myeloid

Purpose Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age. Patients and Methods In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs. Results Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients ≥ 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients ≥ 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61). Conclusion Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.

scholarly journals Upregulation of HOTAIR Predicts Poor Outcome in Acute Myeloid Leukemia

2019 ◽  
pp. 1-7
Author(s):  
Nashwa EL-Khazragy ◽  
Magdy m. Mohamed ◽  
Odett M. Zaky
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Outcome ◽  
Transcriptional Level ◽  
Hematopoietic Malignancy ◽  
Expression Levels ◽  
De Novo Aml ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, in spite of the marked improvement in the treatment of AML; Molecular biomarkers open the door to improve disease outcome. Accumulating evidence suggested that the long non-coding RNA “HOTAIR” has an oncogenic role in hemopoietic malignancies. Recently, it has been evident that knockdown of HOTAIR inhibits cell proliferation and induces apoptosis by modulating c-Kit expression via acting as competing for endogenous RNAs (ceRNAs) to sponge miR-193a at the post-transcriptional level. Objectives: we aimed to evaluate the diagnostic and prognostic value of HOTAIR in AML, to investigate its association with and c-Kit and miR-193a. Subjects & Methods: we examined the expression levels of HOTAIR, miR-193a, and c-Kit in 100 de-novo AML patients using quantitative, the association of genes expressions with risk factors and patient’s outcome were statistically analyzed. Results: the expression of HOTAIR was significantly upregulated by four folds in AML compared to healthy controls; higher expression levels were associated with high-risk factors, poorer overall survival (OS) and shorter leukemia-free survival (LFS). In addition; a negative correlation was detected between Lnc-HOTAIR and miR-193a, although significance didn’t reach. Conclusion: The obtained results suggested that HOTAIR expression was upregulated in peripheral blood samples of de-novo AML patients and was associated with leukemic burden and disease outcome. Therefore, it may represent an effective diagnostic and poor prognostic tool for AML.

Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2387-2392 ◽  
Author(s):  
Lee-Yung Shih ◽  
Chein-Fuang Huang ◽  
Jin-Hou Wu ◽  
Tung-Liang Lin ◽  
Po Dunn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Residual Disease ◽  
Adult Patients ◽  
Single Mutation ◽  
Wild Type ◽  
First Relapse ◽  
Acute Myeloid

Analysis of internal tandem duplications of FLT3(FLT3/ITD) was performed on bone marrow samples obtained at diagnosis and relapse from 108 adult patients with de novo acute myeloid leukemia (AML) to determine the role of this mutation in leukemic relapse. Eighty-three patients had wild-type FLT3at both diagnosis and relapse, 16 had FLT3/ITD at both stages, whereas 8 had acquired the mutation and 1 had lost it at relapse. Using Genescan analysis, we found that FLT3/ITD levels at first relapse were significantly higher than those at diagnosis (mean ± SE, 40.5% ± 4.8% versus 17.9% ± 3.6%,P < .001). The increase in mutation levels at relapse as compared with diagnosis did not correlate with the difference in blast cell percentages at both stages (P = .777). A hemizygous deletion of wild-type FLT3 was found in 4 patients at relapse compared to none at diagnosis. Nine of the 11 patients carrying a single mutation at diagnosis relapsed with an identical mutation. All 6 patients with more than one FLT3/ITD mutation at diagnosis showed changes in mutation patterns and levels at first relapse; however, each patient retained at least one mutation in the relapse sample. The changes of mutation patterns had implications for the monitoring of minimal residual disease. Our results suggest thatFLT3/ITD may contribute as the initial transforming event in AML, and relapse can reflect the selection and outgrowth of a mutant clone or evolution of a new clone harboring this mutation.

Prognostic Factors in Adult Patients up to 60 Years Old With Acute Myeloid Leukemia and Translocations of Chromosome Band 11q23: Individual Patient Data–Based Meta-Analysis of the German Acute Myeloid Leukemia Intergroup

2009 ◽  
Vol 27 (18) ◽  
pp. 3000-3006 ◽  
Author(s):  
Jürgen Krauter ◽  
Katharina Wagner ◽  
Irina Schäfer ◽  
Rolf Marschalek ◽  
Claus Meyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Adult Patients ◽  
Chromosome Band ◽  
Reciprocal Translocations ◽  
Acute Myeloid

Purpose To identify risk factors for induction success and overall survival (OS) and relapse-free survival (RFS) and to evaluate the impact of allogeneic stem-cell transplantation (alloSCT) in adult patients up to 60 years old with acute myeloid leukemia (AML) and reciprocal translocations involving chromosome band 11q23 [t(11q23)]. Patients and Methods An individual patient data-based meta-analysis was performed on 180 adult patients with AML and t(11q23). These patients were identified by cytogenetics and/or molecular techniques and treated within eight prospective multicenter trials of the German AML Intergroup. The median follow-up time was 53 months. Results Complete remission rate was 71%. Favorable factors for induction success were the presence of a t(9;11), t(11q23) as a sole aberration, and de novo leukemia. OS rate at 4 years was 29%. Translocations other than t(9;11), platelets less than the median, secondary leukemia, and peripheral blasts greater than the median were adverse risk factors for OS. RFS rate at 4 years was 29%. The presence of a t(6;11) and peripheral blasts greater than the median had a negative impact on RFS. Three risk groups for OS and RFS could be defined by the combination of these factors with 4-year OS rates of 50%, 28%, and 5% and 4-year RFS rates of 37%, 26%, and 5%. An alloSCT from matched related or unrelated donors in first complete remission was beneficial, especially in t(6;11)-negative patients. Conclusion Risk stratification of AML patients with reciprocal translocations of chromosome band 11q23 is feasible based on the translocation partner and clinical parameters.

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.

Sign in / Sign up

Export Citation Format

Share Document