scholarly journals Treatment Outcomes of Pediatric Acute Myeloid Leukemia in the Yeungnam Region: A Multicenter Retrospective Study of the Study Alliance of Yeungnam Pediatric Hematology–Oncology (SAYPH)

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 109
Author(s):  
Jae Min Lee ◽  
Eu Jeen Yang ◽  
Kyung Mi Park ◽  
Young-Ho Lee ◽  
Heewon Chueh ◽  
...  

Acute myeloid leukemia (AML) is the second most common pediatric leukemia, with a survival rate of 70%. In this retrospective study, we evaluated the treatment outcomes of pediatric AML among 144 patients diagnosed between 2000 and 2013. After induction, 80.6% of patients achieved complete remission (CR). The 5-year overall survival (OS) and event-free survival (EFS) rates were 58.8 ± 4.2% and 49.8 ± 4.2%, respectively. Based on the response to induction therapy, the 5-year OS was 66.9 ± 5.7% in patients with CR (p < 0.001). Ninety-nine patients with CR after induction therapy were examined, and their 5-year OS and EFS were 66.4 ± 4.9% and 56.3 ± 5.1%, respectively. The 5-year OS rates according to treatment were 59.9 ± 7.4% in the chemotherapy group and 72.3 ± 6.3% in the hematopoietic stem cell transplantation (HSCT) group (p = 0.089). The EFS was 50.1 ± 7.4% in the chemotherapy group and 61.7 ± 6.9% in the HSCT group (p = 0.098). OS and EFS according to cytogenetics were insignificant. Our findings confirmed that the response to induction treatment was important for survival and HSCT had no significant survival benefits compared with those of chemotherapy. Moreover, many early induction deaths under the age of 2 years were observed.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3618-3618
Author(s):  
Stephany Corrêa ◽  
Eliana Abdelhay ◽  
Peter Paschka ◽  
Verena I. Gaidzik ◽  
Rocio Hassan ◽  
...  

Abstract Introduction: Over the last years, there has been a tremendous increase in understanding acute myeloid leukemia (AML) biology and a great effort has been taken in order to improve AML chemotherapy strategies. However, the growing knowledge of leukemia associated molecular mechanisms just started to translate into improved outcome. With regard to conventional chemotherapy multidrug resistance (MDR) is a persisting problem and the impact of ABCB1 (MDR1) expression is still controversially discussed. Methods: In this study we evaluated the ABCB1 expression using qRT-PCR and gene expression profiling (Affymetrix U133plus2.0 arrays) in 250 diagnostic AML samples derived from patients enrolled on a prospective treatment trial of the German-Austrian AML Study Group (AMLSG 07-04 trial; NCT00151242), in which patients were treated with an intensive anthracycline/cytarabine-based induction therapy. Findings were also evaluated in 154 TCGA AML cases receiving a 7+3 induction treatment (data available at http://cancergenome.nih.gov/) and put into perspective with previous reports. Furthermore, we investigated ABCB1 expression associated gene signatures and examined epigenetic regulation mechanisms by COBRA and methyl-CpG immunoprecipitation sequencing (MCIp-seq) in selected cases. Results: Our global analysis showed that patients who obtained a complete response (CR) following double induction therapy had lower ABCB1 mRNA levels compared to patients with refractory disease (RD) (p=0.07). Regarding cytogenetic AML subtypes, ABCB1 mRNA levels varied among the different cytogenetic groups with the complex karyotype group showing the highest ABCB1 and the inv(16) group the lowest ABCB1 expression levels. A comparison of CR versus RD cases within the cytogenetically determined prognostic groups showed that in the intermediate [CN-AML, t(11q23), and other intermediate risk cytogenetic aberrations (othersinter)] and poor risk groups (complex karyotype and othershigh), RD patients presented with significantly higher ABCB1 mRNA levels (p=0.02). Similarly, patients with favorable risk cytogenetics [t(8;21) and inv(16)], who achieved a CR, presented with lower ABCB1 levels compared to the ones, who were refractory. Patients with the lowest ABCB1 expression quartile (ABCB1low) showed significantly longer event-free survival (EFS) times than patients in the highest quartile cohort (ABCB1high) (median EFS 322 vs 105 days; p=0.02), while no differences were observed with regard to overall survival. In accordance, there was a significant enrichment of RD cases in the ABCB1high patient group (p=0.03). Next, in order to better understand the regulation of ABCB1 in AML, we specifically evaluated the DNA methylation level of a previously identified GC box important for ABCB1 expression regulation in CML and we performed global analyses of the entire ABCB1 5' region. While both analyses did not reveal significant differences, further investigation of an ABCB1 associated gene pattern showed a correlation with CD34 and KIT expression (p<0.001). This suggests that like in CML, ABCB1 might be regulated by WNT, and in line, normal CD34+ hematopoietic stem cells also showed high ABCB1 expression levels. Conclusions: In summary, our data provide further evidence for a potential impact of ABCB1 deregulation on the response to AML chemotherapy, especially in more stem cell like leukemia cohorts as well as cytogenetically high risk AML. While we are currently further investigating the involvement of the Wnt/β-catenin pathway in the regulation of ABCB1 transcription in AML, further integration of molecular findings are warranted to better decipher the underlying drug resistance mechanisms. Ultimately, these analyses will improve patient management by adding valuable predictive biomarkers. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2728-2728
Author(s):  
Tingting Shao ◽  
Yuan Feng ◽  
Ninghan Zhang ◽  
Rong Wang ◽  
Ting Pan ◽  
...  

Background: Acute myeloid leukemia (AML) is an aggressive hematological disease. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and chemotherapy are major treatment regimens for AML. However, prognostic markers cannot guide the decision for a specific treatment, as they are related with a various prognosis regardless of the given treatment. HOXA (homeobox A) genes cluster could promote tumor survival, proliferation, invasion, and increase the resistance of AML. The aim of this study was to screen potential miRNAs (microRNAs) that would target HOXA genes, and evaluate the utility of miRNAs in AML, help patients choose a better treatment between chemotherapy and allo-HCST. Methods: Clinical data and RNA-Seq expression data of selected cases were provided by The Cancer Genome Atlas (TCGA). Genome-wide screening was performed to identify miRNA in a heterogeneous AML population. Univariable Cox proportional hazards models and Multivariable Cox proportional hazards models were employed to identify whether OS and EFS would be affected by other variables. Results: In this study, totally 162 AML patients were recruited. All patients were firstly divided into the chemotherapy and allo-HSCT groups. Subsequently, according to median values of miR-340, patients were divided into miR-340high and miR-340low expressers, respectively. In chemotherapy group, no difference was found in clinical characteristics, such as the median age, FAB subtypes, karyotypes and genes mutation between miR-340high and miR-340low expressers. However, miR-340low expressers often accompanied with high first relapse rate or death rate in one year than high expressers (P=0.012; 82.2% vs 55.6%). To identify the independent prognostic role of miR-340 in chemotherapy group patients, Univariable and Multivariable Cox proportional hazards models were performed. We found that miR-340lowpatients showed shorter OS (P=0.0005; 5-year OS, 35.6% vs. 5.4%) and EFS (P=0.0005) compared with high expressers. In multivariable analysis, miR-340low patients showed reduced OS (P=0.004; HR: 2.07) and EFS (P=0.01; HR: 1.909) after adjusting other co-variates, such as age, WBC count and several genes mutation in chemotherapy group. Therefore, low miR-340 amounts could be an independent adverse bio-marker in AML patients undergoing chemotherapy. However, in the allo-HSCT group, miR-340 expression level was not associated with outcome in AML patients. To further explore the potential of allo-HSCT in overcoming the adverse characteristics of low miR-340 amounts, the whole 162 patients were regrouped into miR-340low and miR-340high groups. Then patients were divided into chemotherapy and allo-HSCT subgroups. Subgroup analysis revealed that miR-340low patients had significantly longer OS (P<0.0001; HR: 0.316; 95%CI: 0.167-0.459) and EFS (P=0.002; HR: 0.391; 95%CI: 0.231-0.622) in allo-HSCT subgroup than in chemotherapy subgroup (Figure 1). However, in cases highly expressing miR-340, no difference in survival events was detected between the two treatment subgroups. These findings indicated, allo-HSCT may overcome the adverse prognostic effects of low mir-340 expression. Therefore, for low miR-340 cases, early allo-HSCT may be a better option. To explore underlying biological functions of miR-340, we examined gene expression signatures related to the miR-340 expression in AML patients. We observed 135 genes expression levels that associated with miR-340 expression, with 61 and 74 showing positive and negative correlations, respectively. Gene Ontology showed that these genes involved in cellular and developmental processes, transcription regulation, immune system process, cell apoptosis and proliferation, myeloid cell differentiation and hematopoietic organ development. Furthermore, miR-340 expression was negatively correlated with HOXA and HOXB cluster levels. Strikingly, HOXA10, HOXB2, MEIS1 and PRDM16 were predicted miR-340 targets according to in silico analysis. The results hint a prospective regulatory mechanism that links miR-340 to HOXA genes associated with AML. Conclusions: Our data indicate that decreased miR-340 expression predicts an adverse prognosis and allo-HSCT may overcome the potential adverse characteristics of low miR-340 expression. Therefore, lower miR-340 cases should be strongly considered for early allo-HSCT. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3973-3973
Author(s):  
Kyoung Ha Kim ◽  
Dong Hwan Kim ◽  
Su Jin Lee ◽  
Joon Ho Moon ◽  
Myung Hee Chang ◽  
...  

Abstract The bcl-2 protein inhibits apoptosis (programmed cell death) of hematopoietic stem cells induced by a variety of noxious stimuli, thus mediate chemoresistance and decrease chemosensitivity. Higher bcl-2 expression was demonstrated to correlate with an adverse outcome in acute myeloid leukemia (AML). The current study attempted to determine whether BCL2 gene single nucleotide polymorphism (SNP) could affect treatment outcomes of 109 AML patients. Two genotypes were tested including BCL2 −938 C&gt;A (rs2279115) and +21 A&gt;G (rs1801018) using Light cycler-assisted analyses. Neither −938 C&gt;A nor +21 A&gt;G BLC2 genotype was not associated with the difference of the probability to achieve complete remission (CR) after chemotherapy. While −938 A&gt;C BCL2 genotype did not affect leukemia free survival (LFS), event free survival (EFS) or overall survival (OS), of interest, BCL2 +21 A&gt;G genotype correlated with LFS and EFS significantly. The group with +21 AA genotype had a significantly longer median LFS (p&lt;0.001) or EFS (p=0.014), and marginally better OS (p=0.08). The multivariate analyses confirmed that BCL2 gene SNP is independent prognostic factor for LFS (p=0.05, HR 2.57, 95% C.I. [1.02–6.62]) and EFS (p=0.02, HR 2.38, 95% C.I. [1.11–5.13]), but not for OS (p=0.3) considering previously known risk factors. These data indicate that chemotherapy resistance may involve the bcl-2 mediated mechanism in AML.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1011-1011
Author(s):  
Marek Seweryn ◽  
Jerzy Wojnar ◽  
Dariusz Kata ◽  
Slawomira Kyrcz-Krzemien

Abstract Abstract 1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3891-3891
Author(s):  
Akira Shimada ◽  
Yuka Yamashita ◽  
Daisuke Tomizawa ◽  
Akio Tawa ◽  
Tomoyuki Watanabe ◽  
...  

Abstract Background Acute myeloid leukemia harboring internal tandem duplication of fms-like tyrosine kinase 3 (AMLFLT3-ITD) is associated with poor prognosis, but the previous studies have reported that the inferior outcome is only confined to those with high allelic ratio (AR) of ITD/wild type (WT). In our previous AML99 study (2000-2002), AMLFLT3-ITD showed a poor outcome compared to the WT cases (5-year OS; 35% vs. 84%, P<0.0001). We, therefore, assigned all the patients with AMLFLT3-ITD to receive hematopoietic stem cell transplantation (HSCT) in first remission (1CR) in the JPLSG AML-05 study. Patients & Methods AML-05 study, registered at http://www.umin.ac.jp/ctr/ as UMIN000000511, is a Japanese nation-wide multi-institutional study for children (age<18 years) with de novo AML and enrolled 443 eligible patients from Nov. 2006 to Dec. 2010. Cases with acute promyelocytic leukemia or Down syndrome were excluded. FLT3-ITD was examined centrally for all the patients. After the 2 consecutive induction chemotherapies [(ECM: etoposide, Ara-C, and mitoxantrone) and (HCEI: HD Ara-C, etoposide, and idarubicin)], all the AMLFLT3-ITD patients were allocated to the high risk group and further received intensification therapy including HD Ara-C followed by HSCT in 1CR. All DNA samples were extracted from the first diagnostic bone marrow or peripheral blood and subjected to PCR and direct sequencing. AR of FLT3-ITD/WT was examined by GeneScan, and defined AR >0.4 as high and AR ≤ 0.4 as low as previously reported (Meshinchi S. Blood2006). Results We found 47 patients (10.6%) with AMLFLT3-ITD in this study (30 males, 17 females, and median age of 11 years at diagnosis). The median WBC count was 65,300/ml (3,690 - 522,050/mL). FAB classification included M1 (n=10), M2 (n=9), M4 (n=9), and M5 (n=11), and AML with normal karyotype was dominant (19/47, 40.4%). Of the 29 patients (61.7%) who achieved CR, twenty-seven received HSCT in 1CR and 19 patients survived (19/27, 70.4%). On the other hand, 14/16 non-CR patients received HSCT, but only 4 survived. The only demographic difference between the 29 CR and 16 non-CR cases was the median WBC count at diagnosis (19,000 vs. 124,000/μL, P<0.001), and rapid clearance of bone marrow blasts after single induction course was observed in the CR group (median blast percentage dropped from 73% to 1.1% in the CR group, while that was 85% to 30.6% in the non-CR group). Finally, five-year OS, DFS and EFS for all 47 AMLFLT3-ITD patients were 41.3%, 58.4% and 36.1%, respectively. AR was analyzed in 44 patients with median ratio of 0.68 (range, 0.11 to 4.47). Median AR was not different between CR vs. non-CR cases (0.53 vs. 0.72). There were no difference in 5-year OS (52.8% vs. 42.5%, P=0.302), DFS (54.5% vs. 64.5%, P=0.524), and EFS (50.0% vs. 34.4%, P=0.283) between patients with low (n=12) and high AR (n=32), however, induction rate was significantly higher in the low AR patients (91.7% vs. 53.1%, P=0.018). It was rather surprising that all FLT3-ITDs were found only in JM domain and not in TKI domain in the current trial. In addition, six of 47 (12.8%) AMLFLT3-ITD patients had NPM1mutation simultaneously, and all received HSCT at 1CR and survived. Discussion and Conclusion We observed a different induction rate between AMLFLT3-ITD patients with low and high AR, but poor final outcomes in both. Regardless of the level of AR, patients with AMLFLT3-ITD, especially who fail to achieve remission, have dismal outcome and effective therapy combined with novel FLT3 inhibitor is urgently needed to overcome the disease. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5175-5175
Author(s):  
Liyan Fan ◽  
Aili Chen ◽  
Yixin Hu ◽  
Peifang Xiao ◽  
Jun Lu ◽  
...  

Abstract Background: It is difficult for pediatric refractory and relapse acute myeloid leukemia (RR-AML) and MDS-RAEB/RAEBT patients to achieve complete remission (CR) and these patients develop recurrence and die of either disease progression or associated complications. The CAG regimen (cytarabine, aclarubicin and G-CSF) has been widely used in treating patients with MDS-EB and AML-MRC in Asia. Likely, Short term CAG derived regimens called low dose induction therapy, MAG regimen (Mitoxantrone for 3 doses, cytarabine and G-CSF for 10 days) also showed efficacy in De Novo AML. However, MAG regimen showed less efficacy in RR-AML and MDS-5(5q-). Purpose: To evaluate the clinical efficacy and safety of low-dose decitabine in combination with low-dose MAG regimen (D-MAG regimen) in the treatment of RR-AML and MDS-RAEB/RAEBT. Method A total of 17 patients with MDS-RAEB/RAEBT and RR-AML((2 cases of MDS-RAEB, 3 cases of MDS-RAEBT, 10 cases for refractory AML, and 2 cases for relapse AML) from June 2017 to April 2018 in our center were included in the retrospective study. All the patients were treated with decitabine of 20 mg/m2 for 5 days and followed by 10 days of MAG regimen (cytarabine of 10mg/m2 q12h for 10 days, mitoxantrone of 5 mg/ m2.d for 3 days, and G-CSF of 5μg/kg.d for 10 days),called D-CAG regimen. After two cycles of induction chemotherapy, the patients who obtained CR received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results Among a total of 17 patients, the median age was the median age was 102 months (32-200 months) and 64.71 % of them were male. Characteristic features of these patients were illustrated in Table 1. Only 2 cases died of severe lung infection due to continuous agranulocytosis who had been received high dose induction therapy (Daunorubicin of 50mg/M2.d for 3 days, cytarabine of 100mg/m2 q12h for 10 days, and Etoposide of 150mg/m2.d for 5 days) for 2 cycles with poor physical condition before D-MAG. In the other 15 cases, 10 of them had complete remission (CR) after the first course of treatment, 4 cases were partial remission (PR), 1 case with a high blast cells at 25% indicated a poor response to D-MAG, and the effective rate was 93.3%. Among 4 children with PR, one case reached CR after the second courses of treatment. The most common adverse reactions in all children were hematological toxicity, grade III-IV. Liver damage was found in 2 cases, grade I and grade II respectively. There were 3 cases of oral side reactions, 1 case in grade I and 2 cases in grade II. The gastrointestinal reactions in all children were grade I - II. By July 2018, the median follow-up was 11 months (7-16months). Among 15 patients after D-MAG, 11 patients received HSCT. The twelve-month survival rate was 88.24% and the median leukemia-free survival (LFS) was 11 months. Conclusion The low-dose decitabine in combination with Low-dose MAG regimen improved CR rate for pediatric patients with MDS-RAEB and RR- AML, and is a promising treatment for pediatric patients with MDS/RR-AML. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
kaixun hu ◽  
Mei Guo ◽  
Chang-Lin Yu ◽  
Jian-Hui Qiao ◽  
Qi-Yun Sun ◽  
...  

Abstract BackgroundThe treatment outcomes of elderly patients aged over 70 with acute myeloid leukemia (AML) have been very disappointing. In comparison, our designed HLA-mismatched hematopoietic stem cell micro-transplantation (MST) has achieved such encouraging treatment results in AML patients as might warrant further investigations of the outcomes of MST for the above mentioned patients. MethodsOne hundred and eleven patients aged 70-88 years were enrolled. Eighty patients were assigned to the high-risk MST or standard MST group according to high-risk prognostic factors. The other thirty-one patients were assigned to either the chemotherapy group or support group. After receiving induction chemotherapy with cytarabine and anthracycline, patients who achieved complete remission (CR) were given another 2 cycles of post-remission therapy with cytarabine. Each chemotherapy regimen was followed by donor stem cell infusion in the MST groups. ResultMST achieved an encouragingly high CR rate in patients (63.8%), even in high-risk patients (54%). It was significantly higher than that in the chemotherapy alone group. The 1-year overall survival (OS) of MST patients was 57.7% and was 68.6% in the high-risk and standard group, respectively, whereas the OS was only 37.3% in the chemotherapy group. The severe infection rate was 36% and 54% in MST and chemotherapy group. No GVHD was observed in MST patients. A larger updated T cell clones was observed in MST patients by T cell receptor repertoire analysis with a Next Generation Sequencing methodology. ConclusionsThese results suggested that MST is a safe and practical treatment regimen conducive to a longer-term survival for AML patients at a highly advanced age.


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