Acute myeloid leukemia (AML) is a rare type of childhood acute leukemia, which has a worse prognosis than childhood acute lymphoblastic leukemia. Over the past decade, significant progress has been made in the treatment of childhood AML and the 5-year event-free survival rate may be as high as 70% in developed countries. This survival improvement is largely attributable to risk-stratified treatments, therapies tailored to individual patients based on the biological characteristics of the disease, and continuously improving supportive care. An accurate diagnosis is the prerequisite for risk stratification, prognostic evaluation and therapeutic decision making. How to reduce early mortality and thus improve overall survival, how to implement appropriate supportive treatment to reduce treatment-associated complications, and how to reduce treatment-related mortality are the key to the improvement of therapies for childhood acute myeloid leukemia.
Child ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics

At present, acute myeloid leukemia (AML) accounts for about 15%-20% of childhood acute leukemia. Although overall survival rate is increasing with the help of risk stratification, stratification of chemotherapy, and supportive treatment, conventional pharmacotherapy still has a limited clinical effect and certain limitations in improving remission rate in previously untreated patients and reducing recurrence after remission. With the development of precision medicine, the mechanisms of targeted therapy, including abnormal activation of AML-related signaling pathways and epigenetic modification, have been found in recent years. Molecular-targeted drugs can therefore act on specific receptors and target genes to improve clinical effect and the prognosis of AML patients.
Child ; Epigenesis, Genetic ; Humans ; Immunotherapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Molecular Targeted Therapy

Aged ; Aged, 80 and over ; China ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; mortality ; Middle Aged

BACKGROUND: To evaluate the effects and toxicity of combination chemotherapy using idarubicin (IDA) plus BH-AC as an induction regimen, we studied two groups of patients with adult acute myeloid leukemia (AML) who received IDA plus either Sunrabin(r) or Enoron(r). METHODS: Twenty-four and twenty-five patients in each group eligible for the induction study were enrolled. The remission induction therapy consisted of IDA 12mg/m2 intravenously for three consecutive days in combination with two kinds of BH-AC, that is Sunrabin(r) or Enoron(r), 300mg/m2 intravenously for seven days. Additional augmentation treatment with BH- AC was given for 3 days based on the results of bone marrow examination performed on the seventh day following initial treatment, i.e. depending on the ratio of the remaining leukemic cells. RESULTS: Complete remission was achieved in 75% vs 74% of each group of patients. The treatment-related mortality during induction chemotherapy was 1 patient in each group. There was no statistical difference in the level of toxicities between two groups. The most frequent side effect after these combination chemotherapy was manageable mucositis. Enoron(r) group showed rather rapid recovery of peripheral blood counts than those of Sunrabin(r) group. CONCLUSION: This study indicate Enoron(r) is comparable to Sunrabin(r) which can be used as an effective induction chemotherapeutic agent in adult patient with AML.
Adult* ; Bone Marrow Examination ; Drug Therapy, Combination ; Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Mortality ; Mucositis ; Remission Induction

BACKGROUND: Standard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown. METHODS: We analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5–20% and >20% on day 7 of 3+7, respectively. RESULTS: Early intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11–3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55–0.93, P=0.012). CONCLUSION: Early intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.
Adult* ; Aged ; Bone Marrow ; Cytarabine ; Drug Therapy* ; Humans ; Idarubicin ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Mortality ; Multivariate Analysis ; Recurrence ; Remission Induction

OBJECTIVETo study WT1 gene expression in children with acute myeloid leukemia (AML) and its possible correlations to clinical outcomes.

METHODSBone marrow samples were collected from 45 children with AML (excluding acute promyelocytic leukemia, AML-M3) at different time points of AML treatment and follow-up. WT1 gene expression levels in bone marrow mononuclear cells were assayed by real-time fluorescence quantitative PCR. The correlation between WT1 expression and prognosis was retrospectively analyzed.

RESULTSThe WT1 expression level in AML children with bone marrow blast cell percentage of >60% was significantly higher than in those with bone marrow blast cell percentage of ≤ 60% (p<0.05). The lower WT1 expression level was documented in children with AML-M2 compared with in children with other non-M2 subtypes (p<0.05). WT1 expression level in patients in complete remission was significantly lower than that in patients at diagnosis or relapse (p<0.01). The 2-year disease-free survival (DFS) in patients with higher WT1 expression was significantly lower than in those with lower WT1 expression at the end of induction chemotherapy (p<0.05). The 2-year overall survival (OS) and DFS in patients with ≥1 log WT1 reduction range were significantly higher than those with <1 log reduction of WT1 expression level at the end of induction chemotherapy (p<0.05). WT1 expression levels tended to rise 2-3 months prior to bone marrow relapse.

CONCLUSIONSWT1 expression level is closely correlated prognosis in children with AML. Dynamic monitoring of WT1 expression level is of great clinical importance in terms of individualized management, prognosis evaluation and relapse prediction.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; mortality ; Male ; Recurrence ; WT1 Proteins ; genetics

The objective was to study the incidence and prognosis significance of -7/7q- abnormalities in acute leukemia and myelodysplastic syndrome. Conventional cytogenetic analysis of R-band was used to test -7/7q- chromosome abnormalities in 410 patients with acute leukemia (AL), in 71 cases of myelodysplastic syndrome (MDS) and in 36 cases of chronic myelogenous leukemia in accelerated phase (CML-AP). The results showed that the incidences of -7/7q- abnormalities in AL, MDS and CML-AP patients were 4.88%, 9.86% and 8.33% respectively. The -7/7q- abnormalities could be found in acute myeloblastic leukemia (AML) and acute lymphocytic leukemia (ALL), incidences of which were 4.70% and 6.25% (P > 0.05) respectively. 9 cases had -7 or 7q- as the sole chromosome abnormalities, 22 cases showed other additional chromosome abnormalities: -X, -5, +8, t(3; 3), t(11;16) and t(2;11). Monosomy -7 and 7q- abnormality clone was found in one patient with MDS-RAEB, and the number of cells with -7 abnormality was greater than that of 7q- abnormality cells. Four patients acquired CR among 7 patients with ALL after chemotherapy, but 2 out of 13 patients with AML achieved CR while 6 out of 7 patients with MDS transformed into AL. No patients with CML-AP achieved CR. In conclusion, -7/7q- is a frequent aberration in hematologic malignancies as well as AML and ALL. The monosomy -7 and 7q-abnormalities were detected in the same patient. The patients with -7/7q- abnormalities show poor prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Chromosomes, Human, Pair 7 ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; mortality ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; genetics ; mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; mortality

PURPOSE: The effect of salvage chemotherapy using mitoxantrone based regimen for refractory AML (RAML) was analyzed. METHODS: Between January 1990 and March 2001, we treated 26 RAML. Ten patients received salvage chemotherapy with mitoxantrone based regimen and 16 patients with regimen devoid of mitoxantrone. RESULTS: Of total 54 AML patients treated during this period, 48 cases were available for analysis. RAML patients were 26 cases (54.1%) and M:F ratio was 2.3:1. FAB M2 and M4 were 8 each, and 7 cases were M7. There were 1 case of M1, M5 and M6 each. Eleven (42.3%) of them showed chromosomal abnormalities with variable karyotypes. Patients on mitoxantrone regimen all achieved complete remission (CR), while mitoxantrone devoid regimen achieved CR in only 56.2%. Allogeneic bone marrow transplantation was done in 5 cases (19.2%) of RAML, who are all alive with the median survival duration of 18 months. In mitoxantrone based regimen, 4 cases developed congestive heart failure and 5 had severe infection due to prolonged myelosuppression. In non-mitoxantrone group, 5 of 7 cases who failed to achieve CR died of sepsis. CONCLUSION: The mortality of RAML patients who are refractory to salvage chemotherapy remains very high. This study suggests that mitoxantrone based chemotherapy is effective in achieving complete remission as well as in prolonging survival in RAML patients.
Bone Marrow Transplantation ; Child* ; Chromosome Aberrations ; Drug Therapy* ; Drug Therapy, Combination ; Heart Failure ; Humans ; Karyotype ; Leukemia, Myeloid, Acute* ; Mitoxantrone* ; Mortality ; Remission Induction* ; Sepsis

BACKGROUND: The therapeutic outcome for refractory or relapsed acute myeloid leukemia (AML) is very poor; it is difficult to expect the long-term disease free survival in these patients. We evaluated the therapeutic outcome of a salvage chemotherapy consisting of high- dose cytarabine and idarubicin. METHODS: From December 1995 to September 2000, 20 patients (12 patients with primary refractory AML and 8 patients with first relapsed AML) were treated with the regimen that included cytarabine 3.0g/m2 (1.5g/m2 for patients >or=50 years of age) over 3 hours every 12 hours for 12 doses (D1-6, total 36g/m2) plus 12mg/m2 idarubicin for 3 days (D2-4) by intravenous infusion. RESULTS: The complete remission (CR) rate was 55.0% (95% confidence interval, 31.2 ~ 78.8%): 58.3% (7 of 12) for refractory AML and 50.0% (4 of 8) for relapsed AML. The causes of remission induction failure were resistant disease (15.0%, 3 of 20) and early death from infection (30.0%, 6 of 20). The median duration of disease free survival of the CR patients was 15 months (range, 1~59 months) and the median duration of overall survival of all patients was 6 months (range, 0~61 months). The median time of neutrophil recovery over 500/nL from the initiation of chemotherapy was 31 days and the median time of platelet recovery over 20X10(3)/nL was 32 days. For a total of 20 patients, grade 3 and 4 toxicity were observed in 20.0% for nausea/vomiting, 20.0% for diarrhea and 5.0% for stomatitis. CONCLUSIONS : We found that a combination chemotherapy of high-dose cytarabine and idarubicin was an effective salvage regimen for patients with refractory or relapsed acute myeloid leukemia. However aggressive supportive care is necessary to minimize the treatment related morbidity and mortality resulting from prolonged myelosuppression.
Blood Platelets ; Cytarabine* ; Diarrhea ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Idarubicin* ; Infusions, Intravenous ; Leukemia, Myeloid, Acute* ; Mortality ; Neutrophils ; Remission Induction ; Stomatitis

To explore the Fas and mdr-1 expression and their correlation in multidrug resistance (MDR), Fas and mdr-1 expressions of bone marrow from 59 patients with newly diagnosed AL before therapy and after complete remission were detected by direct immunofluorescence with flow cytometry and semi-quantitative RT-PCR, respectively. The results showed that in newly diagnosed AL patients, Fas expression in AML was higher than in ALL (P < 0.05), mdr-1 expression in AML and ALL had no difference (P > 0.05), the expressions of Fas and mdr-1 had correlation (r = -0.282, P < 0.05) in AL; the results of simple-variable and multivariable COX survival factor model analysis suggested that Fas and mdr-1 expressions were prognostic factors for the effect of therapy and survival. Log rank test, comparing the groups of Fas(+) with Fas(-), mdr-1(+) with mdr-1(-), demonstrated that the CR rates and median remission time of every two groups had significant difference. It is concluded that in AL, Fas and mdr-1 expressions have high correlation with the effect of treatment, Fas expression probably is one of the favorable prognostic factors, mdr-1 is an unfavorable prognostic and less effective factor.
Adolescent ; Adult ; Aged ; Child ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Genes, MDR ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; metabolism ; mortality ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; metabolism ; mortality ; RNA, Messenger ; analysis ; fas Receptor ; analysis