scholarly journals MutatedWT1,FLT3-ITD,andNUP98-NSD1Fusion in Various Combinations Define a Poor Prognostic Group in Pediatric Acute Myeloid Leukemia

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Naghmeh Niktoreh ◽  
Christiane Walter ◽  
Martin Zimmermann ◽  
Christine von Neuhoff ◽  
Nils von Neuhoff ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Protocols ◽  
Pediatric Acute Myeloid Leukemia ◽  
Poor Survival Outcome ◽  
Life Threatening ◽  
Prognostic Group ◽  
Poor Outcomes ◽  
Acute Myeloid

Acute myeloid leukemia is a life-threatening malignancy in children and adolescents treated predominantly by risk-adapted intensive chemotherapy that is partly supported by allogeneic stem cell transplantation. Mutations in theWT1gene andNUP98-NSD1fusion are predictors of poor survival outcome/prognosis that frequently occur in combination with internal tandem duplications of the juxta-membrane domain ofFLT3(FLT3-ITD).To re-evaluate the effect of these factors in contemporary protocols, 353 patients (<18 years) treated in Germany with AML-BFM treatment protocols between 2004 and 2017 were included. Presence of mutatedWT1andFLT3-ITDin blasts (n=19) resulted in low 3-year event-free survival of 29% and overall survival of 33% compared to rates of 45-63% and 67-87% in patients with only one (onlyFLT3-ITD; n=33,onlyWT1mutation; n=29) or none of these mutations (n=272). IncludingNUP98-NSD1and high allelic ratio (AR) ofFLT3-ITD(AR ≥0.4) in the analysis revealed very poor outcomes for patients with co-occurrence of all three factors or any of double combinations. All these patients (n=15) experienced events and the probability of overall survival was low (27%). We conclude that co-occurrence ofWT1mutation,NUP98-NSD1,andFLT3-ITDwith an AR ≥0.4 as triple or double mutations still predicts dismal response to contemporary first- and second-line treatment for pediatric acute myeloid leukemia.

scholarly journals Occurrence of Acute Myeloid Leukemia in Young Pregnant Women

2008 ◽  
Vol 1 ◽  
pp. CMBD.S823
Author(s):  
Juliane Menezes ◽  
Mariana Emerenciano ◽  
Flávia Pimenta ◽  
Gilson Guedes Filho ◽  
Isis Q. Magalhães ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Young Women ◽  
Acute Leukaemia ◽  
Myeloid Leukemia ◽  
Leukemic Cells ◽  
Fusion Genes ◽  
Life Threatening ◽  
Poor Outcomes ◽  
Acute Myeloid ◽  
In Pregnancy

Although acute leukaemia is rare in pregnancy its importance lies in its life-threatening potential, both to the child and the mother. The possibility of vertical transmission of leukemic cells increases the attention devoted to these patients and their offspring. Three cases of pregnant young women (15-17 years of age) with AML are presented. This series of cases is the first report where gene abnormalities such as ITD mutations of the FLT3 gene and AML1/ETO fusion genes were screened in pregnant AML patients and their babies, so far. Unfortunately, very poor outcomes have been associated to similar cases described in literature, and the same was true to the patients described herein. Although very speculative, we think that the timing and possible similar exposures would be involved in all cases.

The Presence of Central Nervous System Disease at Diagnosis in Pediatric Acute Myeloid Leukemia Does Not Affect Outcome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1827-1827
Author(s):  
Donna L. Johnston ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Beverly J. Lange ◽  
William G. Woods
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Study Entry ◽  
Pediatric Acute Myeloid Leukemia ◽  
Cns Disease ◽  
Acute Myeloid

Abstract Introduction: The presence of disease in the central nervous system (CNS) in pediatric acute myeloid leukemia (AML) is often thought to confer a worse prognosis. This study examined the outcome of children with AML who had CNS disease at diagnosis. Methods: Patients enrolled on Children’s Oncology Group protocols 2891 (N=836)and 2961 (N=901) being treated for de novo AML were classified for the presence of CNS disease at diagnosis as: CNS1 (less than 5 WBC in the CSF with no blasts), CNS2 (less than 5 WBC in the CSF with blasts) or CNS3 (5 or more WBC in the CSF with blasts). CNS disease at diagnosis was then analysed for survival, patient characteristics and outcome using univariate analysis. Patients on these protocols were treated with intrathecal chemotherapy and not radiation therapy for their CNS disease. Results: For both AML protocols, the overall survival and event free survival were highest in patients with CNS2 disease but this was not significantly different from the survival of the CNS1 and CNS3 patients. Overall survival from 2891 study entry for all de novo patients Overall survival from 2891 study entry for all de novo patients Overall survival from 2961 study entry for all de novo patients Overall survival from 2961 study entry for all de novo patients Patients with CNS 2 and 3 disease were of significantly lower median age than CNS1 patients (p=0.001 in 2891 and p=0.005 in 2961). There was a significantly higher WBC count at diagnosis (p=0.001 in both studies), presence of hepatomegaly (p=0.001 in both studies), presence of splenomegaly (p=0.003 in 2891 and p=0.001 in 2961), FAB M2 morphology (p=0.001 in both studies) and FAB M4 morphology (p=0.001 in both studies) in patients with CNS2 and 3 disease compared to CNS 1 patients. Also, CNS2 and 3 patients had a significantly higher incidence of abnormal chromosome 16 (p=0.002 in 2891 and p=0.001 in 2961). In protocol 2891 significantly more CNS2 and 3 patients had hyperdiploid cytogenetics compared to CNS1 patients (p=0.016), and in protocol 2961 there were significantly more patients with t(8;21) in the CNS1 group (p=0.007). In terms of overall outcome, there was a significantly higher incidence of isolated CNS relapse in patients with CNS3 disease at diagnosis in the 2891 protocol (p=0.001), and in patients with both CNS2 and 3 disease at diagnosis in the 2961 protocol (p=0.001). Conclusion: Patients with CNS disease at diagnosis have similar survival to those without CNS disease, although they have an increased incidence of isolated CNS relapse. More aggressive CNS directed therapy may be warranted in this patient population.

scholarly journals Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Chi Yeh ◽  
Jen-Yin Hou ◽  
Ting-Huan Huang ◽  
Chien-Hung Lu ◽  
Fang-Ju Sun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Antimicrobial Prophylaxis ◽  
Pediatric Acute Myeloid Leukemia ◽  
Life Threatening ◽  
De Novo Aml ◽  
Susceptibility Profiles ◽  
Acute Myeloid

AbstractLimited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0–18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

scholarly journals Does the Region of Diagnosis Correlate with Overall Survival in Patients with Acute Myeloid Leukemia (AML) - a SEER Review of AML Diagnosis from 2004 - 2007

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1291-1291
Author(s):  
Utkarsh H Acharya ◽  
Mohammed N Kanaan ◽  
Haiyan Cui ◽  
Denise J Roe
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Seer Database ◽  
The West ◽  
East Region ◽  
West Region ◽  
Gender And Age ◽  
Poor Outcomes ◽  
Acute Myeloid

Abstract Background: Epidemiologic features accounting for poor outcomes in patients with acute myeloid leukemia (AML) have been under-reported in the literature. Although it is generally accepted that AML portends an ominous prognosis, there is a paucity of understanding in the etiology and risk factors attributing to such poor outcomes in this condition. We aimed to study the epidemiology and survival outcome of AML and its correlation with the region of diagnosis by reviewing the Surveillance, Epidemiology, and End Result Program (SEER database). Methods: A SEER database (version 8.1.5) review was performed for all age groups with an International Classification of Diseases in Oncology (ICD-O-3) diagnosis of histologically confirmed non acute promyelocytic leukemia (APL)-AML from 2004 -2007. Age of included patients ranged from 15 years to 90 years. Collected variables included date of diagnosis, age at diagnosis, gender, ethnicity, location of diagnosis, reported intervals of follow up, and 3- year overall survival (OS). Primary outcome was 3-year OS correlation with the region/state of diagnosis. All SEER Registries were included in the analysis. Data were analyzed using Kaplan Meier and Cox proportional hazard regression model. Results: A total of 13,238 pts with non APL-AML were identified between 2004 and 2007. The mean age of the overall study population was 61.6 years. The Caucasian to non-Caucasian race ratio was 5:1 and male to female ratio was 7:6. The 3-year OS was 24% in the West region (CA, WA, HA, AL and UT). Patients in East region (NJ, CT) had better 3-year OS (24.5%) when compared with patients in West region. However, patients in Midwest (MI,IW and KY) and South regions (GA, NM and LA) had worse 3-year OS when compared to the West region ( 21.2% and 23.2 % respectively). The 3 year OS was statistically associated with region of diagnosis (P= 0.0003). This conclusion held after adjusting for race, gender, and age with statistical significance (P = 0.0165). Furthermore, the 3 year OS was statistically significant for its association with ethnicity as non-Caucasian groups had better OS compared with Caucasian populations (HR 0.92). However, after adjusting for region, gender and age, the association between OS and ethnicity was not significant (P = 0.588). Conclusion: Non APL-AML OS was statistically associated with the region of diagnosis and presumed treatment based on analysis of all available data. The patients in East region had better survival compared with patients in West region (HR 0.96). However, the patients in South and Midwest regions had poorer survival when compared with the West region (HR 1.01 and 1.13, respectively). This survival difference was statistically significant after adjusting for other confounding factors including age, race and gender. Also the difference in OS among different patient racial populations was not significant when adjusted for the region of diagnosis and treatment. Disclosures No relevant conflicts of interest to declare.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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.

De novo adult acute myeloid leukemia patients’ display at diagnosis functional deregulation of redox balance correlated with molecular subtypes and overall survival

Morphologie ◽  
2019 ◽  
Vol 103 (342) ◽  
pp. 69 ◽  
Author(s):  
Julie Mondet ◽  
Caroline Lo Presti ◽  
Catherine Garrel ◽  
Kristina Skaare ◽  
Clara Mariette ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Molecular Subtypes ◽  
Redox Balance ◽  
Acute Myeloid
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