OBJECTIVETo explore the clinical features and prognosis of primary acute myeloid leukemia (AML) with trisomy 8.

METHODSThe clinical data of 24 cases diagnosed as primary AML with trisomy 8 were collected. The clinical characteristics such as sex, age, subtype of FAB, blood routine and bone marrow blast at the first visit were analyzed and the relationship of the characteristics with CR rate and the prognosis was explored.

RESULTS12 out of 24 AML patients were diagnosed as M5 (50%), while M2, M3, M4 and M6 had 3 cases, respectively (12.5%); one case did not receive the chemotherapy. 23 cases received 1-2 cycles of standard induction chemotherapy. Among them 3 cases of M3 achieved complete response (CR) and survived until the last following up with 100% 5-year OS rate. Among 20 cases of non-M3, 12 cases achieved CR1 (60%), 4 cases achieved partial response (PR) (20%), 4 cases did not respond (NR); 5 cases relapsed in follow-up for 3 years after CR1 (41.7%), 3 cases achieved CR2 after re-induction chemotherapy, and 2 cases remained NR. Among 20 cases of non-M3, 1 case failed to be followed-up after diagnosis within 1 month. The mean follow-up time of 19 cases was 26.2 (1.5-84) months, 9 cases died (6 cases of M5, 1 case of M4 and 2 cases of M2), who achieved PR and NR, or relapsed after CR1; the 3-year DFS and OS were 21%, 31.5% respectively. 2 cases of non-M3 accepted allo-HSCT with HLA-matched sibling donor and kept disease-free survival until the last following up, and survived for 58 and 66 months respectively. Except for 3 cases of M3, 2 cases received allo-HSCT and the cases without chemotherapy, the other 18 cases with initial WBC count less than 10×10(9)/L had OS and DFS longer than those of 10 cases with initial WBC count no less than 10×10(9)/L (P<0.05, P<0.01). The OS of 10 cases with CR1 was longer than OS of those cases without CR1 (P<0.01).

CONCLUSIONThe incidence of trisomy 8 in M5 is higher than the other AML subtypes, and the prognosis of M5 is poor. The initial WBC count above 10×10(9)/L is a high-risk factor. M3 with trisomy 8 and RARA gene has a very good prognosis. Trisomy 8 may increase the risk of primary AML except for M3, so allo-HSCT with HLA-matched sibling donor should be carried out as much as possible after CR1. The gene mutation of FLT3, MLL, HOX11, C-kit, NPM1 may possess an important significance on prognosis.

Bone Marrow ; pathology ; Chromosomes, Human, Pair 8 ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; therapy ; Leukocyte Count ; Prognosis ; Remission Induction ; Trisomy

The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.
Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; *Comparative Genomic Hybridization ; DNA/*analysis/metabolism ; DNA Copy Number Variations ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute/*diagnosis/*genetics/therapy ; Loss of Heterozygosity ; Male ; Myelodysplastic Syndromes/*diagnosis/*genetics/therapy ; *Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Real-Time Polymerase Chain Reaction ; Transplantation, Homologous

No abstract available.
Antineoplastic Agents/*adverse effects/*therapeutic use ; Bone Marrow Cells/metabolism ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*chemically induced/*diagnosis/genetics ; Leukemia, Promyelocytic, Acute/*drug therapy ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Remission Induction ; Tretinoin/therapeutic use

This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.
Adolescent ; Adult ; CCAAT-Enhancer-Binding Proteins ; genetics ; Child ; Female ; Humans ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Mutation ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

This study was aimed to explore the immunophenotyping characteristics of acute myeloid leukemia (AML) and their correlation with the curative efficacy. The bone marrow or blood samples were collected from 516 patients with newly diagnosed AML, and their immunophenotypes were analyzed by flow cytometry. The results showed that (1) In 516 cases, the ratios of myeloid antigen expression were higher, as follows: MPO 95.0%, CD33 93.0%, CD13 88.8%, CD117 69.4%; and the expressions of CD14, CD15, CD64 and CD71 were lower, meanwhile 145 cases were accompanied with lymphocyte antigen expression, the ratios were as follows: CD7 21.5%, CD19 6.0%, CD2 0.78%, CD10 0.58% and CD20 0.58%; the positive expression rate of CD71 in M6 was 100%, and that of CD64 in M5 was the highest (30.2%); the overall positive rate of CD34 was 57.8%. (2) After first chemotherapy, the complete remission (CR) rate was 64.7%, CR rate of CD34(+) patients was lower than that of CD34(-) in M3 group (P = 0.019). The CR rate of CD34(+) patients was significantly lower than that of CD34(-) in non-M3 group (P = 0.002). The CR rate of CD19(+) patients was higher than CD19(-) (P = 0.028); the CR rate of CD7(+) patients was significantly lower than that of CD7(-) (P = 0.002); the CR rate of CD71(+) patients was lower than that of CD71(-) (P = 0.013); the CR rate of MPO(+) patients was higher than that of MPO(-) (P = 0.015). Between the CR rate of CD11b, CD13, CD33-positive and-negative group, the difference was not statistically significant (P > 0.05). It is concluded that the phenotype is a prerequisite for the diagnosis of AML, and can help to guide the clinical typing, selection of treatment protocols and evaluation of prognosis.
Adolescent ; Adult ; Aged ; Antigens, CD ; genetics ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Young Adult

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

No abstract available.
Aged ; Ampicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Asian Continental Ancestry Group ; Cytarabine/therapeutic use ; Drug Therapy, Combination ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/complications/*diagnosis/drug therapy ; Male ; Moraxella/genetics/*isolation & purification ; Moraxellaceae Infections/*diagnosis/drug therapy/microbiology ; RNA, Ribosomal, 16S/chemistry/genetics ; Republic of Korea ; Respiratory Tract Infections/diagnosis/microbiology ; Sequence Analysis, RNA ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sulbactam/therapeutic use

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea. METHODS: The study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients. RESULTS: Therapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more common than therapy-related myelodysplastic syndrome (t-MDS). Primary hematologic malignancies that were commonly implicated included mature B-cell neoplasm and acute leukemia. Breast cancer was the most common primary solid tumor. The mean time interval from cytotoxic therapy initiation to t-MN detection was 49 months. Chromosomal aberrations were observed in 35 patients, and loss of chromosome 5, 7, or both accounted for 41% of all cases. Balanced rearrangements occurred in 13 patients; these patients showed shorter latency intervals (mean, 38 months) than patients with loss of chromosome 5 or 7 (mean, 61 months). CONCLUSIONS: In this study, we determined the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN resulting from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.
Adolescent ; Adult ; Aged ; Antineoplastic Agents/*adverse effects/therapeutic use ; Asian Continental Ancestry Group ; Bone Marrow/pathology ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 7 ; Female ; Hematologic Neoplasms/drug therapy/pathology/radiotherapy ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/etiology/genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/etiology/genetics ; Neoplasms, Second Primary/*diagnosis/etiology/genetics ; Republic of Korea ; Young Adult

OBJECTIVETo report two de novo acute myeloid leukemia (AML) patients with t(11;22)(q23;q11.2) and summarize the clinical and biological characteristics.

METHODSBone marrow cells morphology, immunophenotype, chromosome karyotype, fluorescence in situ hybridization (FISH), PCR and gene sequencing were performed. Clinical manifestation and routine laboratory tests were analyzed.

RESULTSThe patients were diagnosed as AML-M₂ and AML-M₅ by morphology and immunophenotype results. Both patients carried t(11;22)(q23; q11.2) and one of them carried an additional chromosome abnormality. MLL-SEPTIN5 fusion transcript was identified in two patients by RT-PCR and sequencing. The two patients got hematologic complete remission after induction chemotherapy with daunorubicin, homoharringtonine, and cytarabine (DHA) or daunorubicin and cytarabine (DA). One of them relapsed and died during consolidation therapy with intermediate-dose cytarabine.

CONCLUSIONLeukemia with t(11;22)(q23;q11.2) chromosome translocation met the clinical and laboratory manifestations of AML. The MLL-SEPTIN5 fusion transcript was the distinctively biological etiology. Patients with t(11;22)(q23;q11.2) were vulnerable to relapse after conventional chemotherapy and had poor prognosis. Allogeneic hematopoietic stem cell transplantation should be recommended as early as possible.

Adult ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 22 ; Female ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; Male ; Prognosis ; Translocation, Genetic

This study was aimed to detect the expression of AML1 fusion genes in the patients with adult acute myeloid leukemia (AML) and further to investigate their association with the progression and prognosis of AML. Bone marrow samples were collected from 168 patients with de novo adult AML, and the expression of AML1 ETO, AML1-EVI1, AML1-MDS1, AML1-MTG16, AML1-PRDM16, AML1-LRP16, AML1-CLCA2 and AML1-PRDX4 was analyzed by a novel multiplex nested RT-PCR. Positive samples and minimal residual disease were further examined by real-time fluorescent quantitative PCR. The results showed that the AML1 fusion genes were found in 10.7% (18/168) patients. Among them, AML1-ETO in 12 (7.1%) cases were detected, AML1-EVI1 in 2 cases (1.2%), and AML1-MDS1, AML1-MTG16, AML1-PRDM16, and AML1-CLCA2 in 1 case (0.6%) each were detected. Among the patients with AML1-ETO, 10 patients (10/12, 83.33%) achieved complete remission (CR) after one cycle of chemotherapy, while 2 patients achieved CR after 2 cycles of chemotherapy. The 2 patients with AML1-EVI1 failed to achieve CR after one cycle of chemotherapy. Patients with AML1-MDS1, AML1-MTG16, AML1-PRDM16, or AML1-CACL2 did not achieve CR after one cycle of chemotherapy. It is concluded that AML1 fusion genes are more frequent and can provide the molecular markers for diagnostics and prognosis evaluation of AML and for monitoring MRD.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Core Binding Factor Alpha 2 Subunit ; genetics ; Female ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Prognosis ; Remission Induction ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult