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

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 investigate the influence factors on survival and outcome of acute myeloid leukemia (AML) patients with t(8;21).

METHODSEighty seven AML patients with t(8;21) after long-term follow-up were enrolled in the analysis of clinical feature, immunophenotype, chromosome karyotype, treatment regimen, as well as the overall survival (OS) and relapse-free survival (RFS).

RESULTSThe overall complete remission (CR) rate was 95.3%. CR rate after first course therapy was 69.8%, after first course therapy containing medium dose Ara-C was 86.2%, and after first course of therapy containing standard-dose Ara-C was 60.3%. The median OS duration was 16.4 months, median RFS 11.7 months, 3 year OS rate 42%, 5 year OS rate 39%, 3 year RFS rate 55% and 5 year RFS rate 55%. Male gender chromosome 9q(-) had statistical significance for shorter OS and poor outcome, 2 courses of post-remission therapy with intermediate dose Ara-C, induction therapy with intermediate-dose Ara-C and post-remission with 4 courses consolidation therapy had statistically longer OS and RFS.

CONCLUSIONSex, chromosome karyotype, induction and consolidation therapy were important influence factors on OS and RFS. Application of intermediate dose Ara-C to induction and consolidation therapy leads to a higher CR rate, prolong OS and RFS.

Adolescent ; Adult ; Aged ; Female ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Prognosis ; Survival Rate ; Translocation, Genetic ; Treatment Outcome ; Young Adult

OBJECTIVE: To investigate the expression of Wilms'tumor 1 () gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1() and Fms-like tyrosine kinase 3-internal tandem duplication (). METHODS: One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high expression (high- group) and those with low expression (low- group), as well as among the patients with or wild type and mutants. RESULTS: The overall response rates (ORR) in high- and low- groups were 65.9% (83/126) and 95.1% (39/41), respectively (<0.01). Compared with the low- group, the high- group had lower 2-y overall survival (OS) rate (46.1% vs. 75.2%, <0.05) and 2-y disease free survival (DFS) rate (43.5% vs. 68.5%, <0.05). After induction chemotherapy, the patients with decreased gene expression ≥ 1log was associated with higher ORR and 2-y OS rate (all <0.05), but the advantage of 2-y DFS rate was not shown (>0.05). In patients with wild type, the high- group had inferior ORR and 2-y OS rate (all <0.05), while in the patients with wild type, the high- group had inferior ORR, 2-y OS rate and 2-y DFS rate (all <0.05). In patients with or FLT3 -ITD mutations, the expression had no significantly predicting values in treatment efficacy and survival (all >0.05). CONCLUSIONS gene overexpression indicated poor prognosis of AML patients; the patients with decreased gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with or wild types.
Disease-Free Survival ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; mortality ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; WT1 Proteins ; genetics ; fms-Like Tyrosine Kinase 3 ; genetics

BACKGROUND: Although cytoplasmic CD79a (cytCD79a) is a highly lineage-specific marker of B lymphoid cells and plays an important role in the diagnosis of acute leukemia, its clinical significance is not fully understood. We aimed to investigate the relationship between cytCD79a positivity and survival probability, and to evaluate the prognostic value of cytCD79a expression in AML with t(8;21) (q22;q22). METHODS: A total of 68 cases of AML with t(8;21)(q22;q22) were diagnosed based on conventional morphology, cytochemistry, flow cytometrty, and cytogenetic and molecular genetic analysis. Immunohistochemistry of cytCD79a was performed retrospectively. Laboratory and clinical findings were reviewed. RESULTS: Five patients among 68 AML with t(8;21)(q22;q22) revealed cytCD79a positive reaction; scores for myeloid lineage/B-lymphoid lineage were 5/3-3.5. Among the five cytCD79a positive patients, only one patient was a child. Three patients were with refractory AML or relapsed, and two patients died within 10 months. Median survival time of cytCD79a positive group was shorter (8.0 months) than that (61.3 months) of cytCD79a negative group. The survival probability of the cytCD79a expression group was significantly lower than classical AML with t(8;21)(q22;q22) (P=0.0001). CONCLUSIONS: These findings emphasize the necessity of investigating cytCD79a, especially in AML with t(8;21)(q22;q22), for a different clinical prognostic value.
Adolescent ; Adult ; Aged ; Antigens, CD79/immunology/*metabolism ; Child ; Child, Preschool ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Cytoplasm/metabolism ; Female ; Humans ; Leukemia, Myeloid, Acute/diagnosis/*genetics/*mortality ; Male ; Middle Aged ; Prognosis ; Survival Analysis ; *Translocation, Genetic