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

OBJECTIVEAcute myeloblastic leukemia (AML) accounts for 15 to 25 percent of childhood acute leukemias. Cytogenetic information is important for diagnosis, classification and prognosis of AML. Our aim was to analyze the relationship between karyotypic characteristics and prognosis of childhood AML.

METHODAccording to karyotypic characteristics, 128 newly diagnosed children AML were separated into 4 subgroups: patients with t(15;17) (group APL), patients with t(8;21)/inv(16) (group A), patients with -7/t(9;22)/complex karyotypes (group C) and the others (group B). Prognoses of these patients were analyzed.

RESULTSThe ages ranged from 1 to 16 years with the mean age of 7 years. 85 boys and 43 girls were included in this study. The 4-year event-free survival (EFS) and overall survival (OS) rates were (55.9 ± 4.7)% and (69.3% ± 4.5)%, respectively. The 4-year EFS and OS of non-M(3)-AML patients were (49.9 ± 5.2)% and (57.1 ± 6.0)%, respectively. The probabilities of 4-year EFS of the four subgroups were (72.2 ± 1.1)%, (66.3 ± 7.7)%, (38.5 ± 9.1)% and (20.1 ± 12.3)%, respectively (P = 0.000). The probabilities of 4-year OS were (92.6 ± 5.1)%, (69.4 ± 7.9)%, (55.6 ± 8.6)% and (30.0 ± 12.3)%, respectively (P = 0.000).

CONCLUSIONCytogenetic aberrations seen in pediatric AML had a significant impact on prognosis.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosome Disorders ; genetics ; Female ; Humans ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; Male ; Prognosis ; Treatment Outcome

The study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with CBFB-MYH11 gene. The clinical data of 12 cases were analyzed retrospectively, including age, clinical characteristics, immunophenotype, treatment protocols and efficacy as well as the prognosis. The results indicated that 12 patients with CBFB-MYH11 were detected in 293 AML patients. The median age of the 12 patients was 32.5 (21 - 57) years old. According to French-American-British (FAB) classification, 66.7% (8/12) patients was diagnosed as M4Eo and 33.3% patients was diagnosed as M4. At new diagnosis, the median WBC count was 19.8×10(9)/L (2.46 - 164.30×10(9)/L). The WBC count > 100×10(9) was found in 16.7% patients (2/12). The complete remission (CR) rate after 1 and 2 cycles of induction chemotherapy were 83.3% and 16.7% respectively, so the total CR rate was 100%. Estimated 5-year relapse-free survival (RFS) and overall survival (OS) were 80% and 83%, respectively. It is concluded that patients with CBFB-MYH11 are usually M4Eo and M4. Patients with this fusion gene are often associated with high frequency of CD33, CD34, CD117, HLA-DR, CD15, CD64 and CD14 expression. Patients with CBFB-MYH11 have a tendency of higher CR rate, longer RFS and OS.
Adult ; Female ; Humans ; Immunophenotyping ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia (AML) with 11q23/MLL gene rearrangements.

METHODSKaryotypes of 234 cases of de novo childhood AML were analyzed using short-term culture of bone marrow cells and R-banding. The fusion transcripts involving MLL gene and partial tandem duplication of MLL (MLL-PTD) were detected by multiple reverse transcription polymerase chain reaction (RT-PCR) assay. Two cases with 11q23 translocation by karyotypic analysis but with negative result of multiple RT-PCR were studied with MLL-dual-color fluorescence in situ hybridization (D-FISH).

RESULTSR-banding karyotypic analysis has revealed 20 cases with 11q23 translocation (14 cases with M5, 4 cases with M4, 2 cases with M2), including 12 cases with t(9;11)(p22;q23), 3 cases with t(1;11)(q21;q23), 2 cases with t(6;11)(q27;q23), 1 case with t(11;19)(q23;p13), 1 with t(5;11)(q31;q23), and 1 with t(X;11)(q24;q23). Eighteen cases with 11q23 translocation having fusion transcripts involving MLL genes were confirmed with multiple RT-PCR; 2 cases showed negative results, but they were confirmed to have MLL rearrangements by D-FISH. MLL-PTD was also detected in 8 cases (4 cases M5, 2 cases M4, M2 and M6, one case each) from the other childhood AML cases. The total incidence of 11q23/MLL gene rearrangements was 11.97% (28/234), and most of patients(85.7%, 24/28) were M4/M5. The complete remission (CR) rate after treatment for the 28 cases with MLL rearrangements was 53.8%, the difference was significant by statistics (P< 0.05) compared with 90.5% for the control group (M4/M5 childhood AML with other karyotypic abnormalities or normal karyotype). Of them, 2 cases receiving intensive chemotherapy survived for 81 and 66 months, respectively, 4 cases receiving allogeneic stem cell transplantation survived for 21, 20, 16 and 11 months, respectively, and are still alive with CR. The medium survival (MS) time for 28 cases with 11q23/MLL rearrangements was 11 months, whereas the MS for control group was 15 months. The difference was not statistically significant(P> 0.05).

CONCLUSIONThe 11q23/MLL rearrangements is highly correlated with the occurrence of monocytic leukemia (M4 and M5). The 11q23 translocation and MLL-PTD are mutually exclusive, though both are indicative of poor prognosis. Intensive chemotherapy and allogeneic stem cell transplantation may ameliorate the clinical outcome. Multiple RT-PCR combined with karyotypic analysis and D-FISH are useful for screening the 11q23/MLL rearrangements in childhood AML.

Adolescent ; Child ; Child, Preschool ; Chromosomes, Human, Pair 11 ; Female ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; genetics ; mortality ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Remission Induction ; Translocation, Genetic ; Treatment Outcome

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

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 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

Inversion of chromosome 16 [inv(16)(p13.1q22)] and t(16;16)(p13.1;q22) are associated with acute myelomonocytic leukemia (AMML) with eosinophilia and a favorable prognosis. On the other hand, patients with del(16)(q22) usually present with MDS or chronic myelomonocytic leukemia (CMML), which can evolve to AMML without eosinophilia, and this chromosomal aberration is associated with older age, a complex karyotype, and a poor prognosis. We report a case of AML with del(16)(q22) which showed a complex karyotype, absence of eosinophilia in bone marrow study and a poor response to chemotherapy.
Antimetabolites, Antineoplastic/therapeutic use ; *Chromosome Deletion ; *Chromosomes, Human, Pair 16 ; Cytarabine/therapeutic use ; Daunorubicin/therapeutic use ; Drug Therapy, Combination ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myeloid, Acute/diagnosis/drug therapy/*genetics ; Male ; Middle Aged ; Monocyte-Macrophage Precursor Cells/cytology ; Prognosis

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