1.Strategies to improve therapeutic efficacy in childhood acute myeloid leukemia.
Chinese Journal of Contemporary Pediatrics 2014;16(2):108-110
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
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Humans
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Leukemia, Myeloid, Acute
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diagnosis
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drug therapy
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genetics
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mortality
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Leukemia, Promyelocytic, Acute
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drug therapy
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genetics
2.Cytogenetic and clinical analysis of -7/7q- abnormalities in acute leukemia and myelodysplastic syndrome.
Hai-Tao MENG ; Wen-Yuan MAI ; Zhi-Mei CHEN ; Ji-Yu LOU ; Jie JIN
Journal of Experimental Hematology 2004;12(4):460-463
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
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Adult
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Aged
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Aged, 80 and over
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Chromosome Aberrations
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Chromosomes, Human, Pair 7
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Female
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Humans
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Leukemia, Myeloid, Acute
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drug therapy
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genetics
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mortality
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Male
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Middle Aged
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Myelodysplastic Syndromes
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drug therapy
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genetics
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mortality
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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drug therapy
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genetics
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mortality
3.Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia.
Hee Jin HUH ; Chan Jeoung PARK ; Seongsoo JANG ; Eul Ju SEO ; Hyun Sook CHI ; Je Hwan LEE ; Kyoo Hyung LEE ; Jong Jin SEO ; Hyung Nam MOON ; Thad GHIM
Journal of Korean Medical Science 2006;21(2):253-258
The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.
Vault Ribonucleoprotein Particles/*genetics
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Survival Rate
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RNA, Neoplasm/genetics
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RNA, Messenger/genetics
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Prognosis
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Neoplasm Proteins/*genetics
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Multidrug Resistance-Associated Proteins/*genetics
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Middle Aged
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Male
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Leukemia, Myelocytic, Acute/drug therapy/genetics/mortality
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Leukemia, Lymphocytic, Acute/drug therapy/genetics/mortality
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Leukemia/drug therapy/*genetics/mortality
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Infant
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Humans
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*Genes, MDR
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Gene Expression
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Female
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Child, Preschool
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Child
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Base Sequence
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Aged
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Adult
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Adolescent
4.Expression of WT1 gene in children with acute myeloid leukemia.
Xue TANG ; Xia GUO ; Xue YANG ; Hui XIAO ; Jing-Jing SUN ; Li-Xing YUAN ; Ju GAO
Chinese Journal of Contemporary Pediatrics 2016;18(12):1211-1216
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
5.Prognostic factors for childhood acute non-mature B-lymphoblastic leukemia.
Hua JIANG ; Long-Jun GU ; Hui-Liang XUE ; Jing-Yan TANG ; Jing CHEN ; Ci PAN ; Jing CHEN ; Chong XU ; Lu DONG ; Min ZHOU
Chinese Journal of Contemporary Pediatrics 2008;10(3):290-294
OBJECTIVETo study the prognostic factors for events-free survival (EFS) in children with acute non-mature B-lymphoblastic leukemia.
METHODSOne hundred and sixty-one children with newly diagnosed acute non-mature B-lymphoblastic leukemia received the ALL-XH-99 protocol treatment. Their medical data, including clinical, biological and molecule features, early responses to treatment (bone marrow evaluation on the 19th day of induction therapy), minimal residual disease (MRD) in bone marrow after remission induction therapy, the risk grade of disease before the beginning of chemotherapy and the outcome, were retrospectively studied.
RESULTSUnivariable analysis indicated that the gender and P170 levels before therapy had no effect on the outcome. Age, initial white blood cell count (WBC), prednisone response, early response to treatment, fusion genes (BCR/ABL or MLL/AF4) and MRD level were significantly related to the EFS (P<0.01). Immunophenotype, myeloid-associated antigen and the risk grade of disease were also related to the EFS (P<0.05). Multivariable analysis showed that WBC >or=50 x 10(9)/L, Cmu positive, BCR/ABL or MLL/AF4 positive and MRD positive (>or=0.01%) were risk factors for the poor prognosis (P<0.01). The early response to treatment was important to modify the therapy protocol.
CONCLUSIONSWBC >or=50 x 10(9)/L, Cmu positive, BCR/ABL or MLL/AF4 positive and MRD positive have important prognostic values in childhood acute non-mature B-lymphoblastic leukemia. Early response to treatment is an important index for modifying the chemotherapy protocol.
Adolescent ; Burkitt Lymphoma ; drug therapy ; mortality ; Child ; Child, Preschool ; Female ; Genes, abl ; Humans ; Infant ; Male ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Neoplasm, Residual ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; Prognosis ; Regression Analysis
6.Biological characteristics of hyperleukocytic acute leukemia.
Journal of Experimental Hematology 2006;14(3):450-454
The study was to investigate the biological characteristics of hyperleucocyte acute leukemia (HAL) and its clinical significance. Immunophenotyping was performed in 48 HAL patients and 73 NHAL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed in 74 patients. The results showed that as compared with NHAL group, HAL group had lower proportion of eryth-lineage in bone marrow (P < 0.05); in AML, the CD14 expression of HAL group was apparently higher than that of NHAL group (P < 0.05); in ALL, HAL group had higher expression of CD8 and lower expression of CD22, cCD79a compared with NHAL group (P < 0.05); the two groups had no significant difference in expression of special lineage antigens and overlapping lineage antigens (P > 0.05). The CR rate of HAL group was lower than that of NHAL group. It is concluded that bone marrow inhibition of HAL group is more severe than that of NHAL group. In AML, monocytic leukemia is easier to become into HAL than other leukemias. In ALL, T-lineage antigens of HAL group are more easily expressed than those of NHAL group; the leukemia cells of HAL group are naiver than those of NHAL group, meanwhile the prognosis of HAL is poor.
Adolescent
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Adult
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Aged
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CD79 Antigens
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biosynthesis
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genetics
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CD8 Antigens
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biosynthesis
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genetics
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Child
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Child, Preschool
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Female
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Humans
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Immunophenotyping
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Leukemia, Myeloid, Acute
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drug therapy
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mortality
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pathology
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Leukocyte Count
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Lipopolysaccharide Receptors
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biosynthesis
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genetics
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Male
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Middle Aged
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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drug therapy
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mortality
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pathology
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Prognosis
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Sialic Acid Binding Ig-like Lectin 2
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biosynthesis
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genetics
7.Clinical and experimental studies of childhood acute myeloid leukemia with 11q23/MLL rearrangements.
Ya-xiang HE ; Yong-quan XUE ; Hong-ying WANG ; Xue-jun SHAO ; Jin-lan PAN ; Jun XU ; Nai-chao YANG ; Zheng-hua JI ; Yi-ping HUANG ; Shao-yan HU
Chinese Journal of Medical Genetics 2012;29(6):677-682
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
8.Efficacy and safety of imatinib for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in children.
Ye GUO ; Tian-Feng LIU ; Min RUAN ; Wen-Yu YANG ; Xiao-Juan CHEN ; Li ZHANG ; Shu-Chun WANG ; Fang LIU ; Jia-Yuan ZHANG ; Xiao-Ming LIU ; Ben-Quan QI ; Yao ZOU ; Xiao-Fan ZHU
Chinese Journal of Contemporary Pediatrics 2015;17(8):819-824
OBJECTIVETo study the efficacy and safety of Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI, imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in children.
METHODSThe clinical data of 53 patients aged less than 15 years when first diagnosed with Ph+ ALL between October 2008 and December 2013 were retrospectively analyzed. The patients were assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).
RESULTSThe complete remission rate and chemotherapy induction-related mortality rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The 3-year event-free survival (EFS) rate in the HR group was (6±5)%; the 5-year EFS rate of the TKI+HR group was (52±11)%. Compared with the HR group, the TKI+HR group had no increase in the toxic responses to chemotherapy and had a decrease in the infection rate during the induction period.
CONCLUSIONSApplication of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.
Adolescent ; Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Imatinib Mesylate ; adverse effects ; therapeutic use ; Male ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; mortality ; Protein Kinase Inhibitors ; therapeutic use
9.Long-term follow-up of treatment outcome and prognosis on 46 children with acute promyelocytic leukemia.
Xiao-Jun XU ; Shu-Wen SHI ; Yong-Min TANG ; Hua SONG ; Shi-Long YANG ; Jian WEI ; Wei-Qun XU ; Bin-Hua PAN ; Ying-Hu CHEN ; Fen-Ying ZHAO ; Hong-Qiang SHEN ; Bai-Qin QIAN ; Ling-Yan ZHANG ; Bo-Tao NING
Chinese Journal of Contemporary Pediatrics 2007;9(1):28-33
OBJECTIVEAcute promyelocytic leukemia (APL) is a specific type of hematopoietic malignancy, accounting for 10% of the de novo acute myeloid leukemia (AML). The data on long-term outcome of APL in children are limited. The aim of this study was to investigate the clinical biological features, diagnosis, prognosis and long-term survival of childhood APL.
METHODSA total of 46 children with newly diagnosed APL from April 1998 to October 2005 were enrolled into this study. Induction treatment containing all-trans retinoic acid (ATRA) plus daunorubicin (DNR) or pirarubicin (THP) was performed on these patients, followed by 6 courses of chemotherapy consolidation: DNR, homoharringtonine or etoposide plus Ara-C. A maintenance therapy was then administered once 3-6 months. The total period of treatment was 2.5 years.
RESULTSOf the 39 patients who had completed the regular treatment, 36 (92.3%) achieved a complete remission. The 5-year cumulative incidence of relapse (CIR) was 28.6%. The estimated overall survival (OS) rates at 1, 3 and 5 years were (86.1 +/- 5.8)%, (76.1 +/- 7.5)% and (70.2 +/- 8.9)% respectively, while the event free survival (EFS) rates were (78.4 +/- 6.8)%, (63.6 +/- 8.7)% and (53.1 +/- 10.0)% respectively. The 5-year OS rate of patients with WBC less than or equal to 10.0 X 10(9)/L was (81.4 +/- 10.3)%, which was significantly higher than that with WBC greater than 10.0 X 10(9)/L[(51.6 +/- 14.7)%, P < 0.05]. Five patients with RT-PCR positive for PML/RARalpha S (short) subtype died eventually although all of them achieved CR, but none of the 13 patients with PML/RARalpha L (long) subtype died.
CONCLUSIONSRemission induction therapy with ATRA + DNR or THP is effective and safe for newly diagnosed childhood APL. The remission induction therapy combined with chemotherapy containing high/intermediate dose Ara-C can improve the long-term survival rates of APL patients. High WBC count and S subtype of PML-RARa are two poor prognostic factors for children with APL.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Leukemia, Promyelocytic, Acute ; drug therapy ; mortality ; Male ; Oncogene Proteins, Fusion ; genetics ; Prognosis ; Survival Rate ; Treatment Outcome ; Tretinoin ; administration & dosage
10.Clinical significance of glucocorticoid induction test in Chinese childhood acute lymphoblastic leukemia.
Jun-jie FAN ; Yi-huan CHAI ; Shao-yan HU ; Hai-long HE ; Wen-li ZHAO ; Yi WANG ; Jie LI ; Jun LU ; Pei-fang XIAO ; Yi-na SUN ; Wei WANG ; Lan CAO
Chinese Journal of Pediatrics 2013;51(7):523-526
OBJECTIVEAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, while glucocorticoid (GC) is a critical component in multi-agent chemotherapy protocols currently used for the treatment of ALL. The purpose of this study was to investigate the relationship between the glucocorticoid induction test and the clinical features and the prognosis of Chinese childhood ALL.
METHODThe study recruited 309 hospitalized patients (187 male and 122 female) with childhood ALL, the sex, age, initial WBC count, immunophenotype, chromosome and gene expression were recorded. After diagnosis, all patients received GC induction test for 7 days. Then they were divided into prednisone good response (PGR) group and prednisone poor response (PPR) group according to the peripheral lymphoblast count on D8. Early responses to chemotherapy and treatment outcomes of the patients in the two groups were also analyzed.
RESULTOf the 309 patients, 263 belonged to PGR group and 46 belonged to PPR group. Initial WBC count was higher in PPR group than in PGR group (86.30×10(9)/L vs. 30.97×10(9)/L, P < 0.01) . B lineage ALL showed more sensitive to GC than T-ALL (86.6% vs. 60%, P < 0.05). Different initial-risk-group's sensitivity to GC differed from one another (high-risk:51.4%, medium-risk: 82.7%, standard risk: 93.7%, P < 0.0125). There was no significant difference between two groups in chromosomal karyotypes (P > 0.05). BCR-ABL positive ALL showed lower sensitivity to GC (P < 0.05) , while MLL, TEL-AML1, E2A-PBX1 positive rates in two groups were of no statistical significance (P > 0.05). Bone marrow was reviewed on D15 and D33, and the CR rates in PGR group were significantly higher than that in PPR group (D15: 60.5% vs. 32.6%, D33: 94.6% vs. 73.3%, P < 0.01) ; Minimal residual disease (MRD) levels were examined on D33, W12, and both were much lower in PGR group (D33: P < 0.01, W12: P < 0.05). Of the PGR group 215 patients (81.7%) remained continuously in complete remission (CCR) while only 28 cases (60.9%) in PPR group did so. The CCR rate was much higher in PGR group than that in PPR group (P < 0.01).
CONCLUSIONClosely related to clinical features and the outcomes of treatment, GC induction test is also an important prognostic factor in Chinese childhood ALL.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; Child ; Child, Preschool ; Female ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukocyte Count ; Male ; Neoplasm, Residual ; drug therapy ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; mortality ; Predictive Value of Tests ; Prognosis ; Remission Induction ; Survival Rate