OBJECTIVE: To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients. METHODS: B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients. RESULTS: There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×10⁹/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×10⁹/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10^-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×10⁹/L, bone marrow MRD >10^-4 at the 12th week were the independent risk factors affecting recurrence of the patients. CONCLUSION Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.
Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Male ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Recurrence ; Retrospective Studies

Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Leukemia, Promyelocytic, Acute ; RNA, Long Noncoding ; Tretinoin

OBJECTIVETo evaluate the therapeutic safety and efficacy of VDMP re-induction regimen in Chinese children with relapsed acute lymphoblastic leukemia (ALL).

METHODSForty-one patients with relapsed ALL were prospectively enrolled in this study. All the patients were distributed in 3 children's hospitals and treated with VDMP regimen as the first re-induction chemotherapy. Therapeutic efficacy and side-effects were analyzed.

RESULTSThe ratio of male to female was 27:14. The median age was 7.9 (2.2-15.4) years old. Patients relapsed at very early, early, and late stage were 7 cases, 11 cases, and 23 cases, respectively.The immunophenotype analysis showed that 38 cases were B-ALL, and 3 cases were T-ALL. All patients suffered from grade 4 of neutropenia and forty(97.6%) cases got infection, of them one case died. Thirty-nine(95.1%) cases had nonhematologic adverse event at least one organ involved grade 3 in 38 out of 41 cases, the VDMP therapy was completed, 34(89.5%) cases achieved a complete remission (CR), 1 case achieved partial remission(PR), and 3 cases didn't get remission. Follow-up data of 38 cases with completing VDMP chemotherapy were obtained, only one case was lost. Among 37 cases available for evaluation, 16 cases received allo-hematopoietic stem cell transplantation(allo-HSCT) after chemotherapy, and 13 patients survived, while 21 cases did not receive allo-HSCT(treated with chemotherapy only), and 8 patients survived.The overall survival rate of allo-HSCT group was significantly higher than that of those treated with chemotherapy only(P<0.05).

CONCLUSIONVDMP re-induction regimen is effective and well tolerable for pafients in the treated children with relapsed ALL. After remission, allo-HSCT is recommended with the aim of long survival.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Remission Induction ; Treatment Outcome

OBJECTIVETo explore the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia (ALL) in high-risk (HR) group.

METHODSA total of 421 children with ALL in the Children's Hospital of Soochow University from August 2008 to March 2013 were diagnosed and treated according to the Chinese Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148 cases were stratified into the low-risk group and 191 cases were included in the moderate-risk group. Eight-two patients of the high-risk group were analyzed retrospectively for their clinical features, 5-year event-free survival (EFS) rate and overall survival (OS) rate.

RESULTSThe median follow-up times of 82 patients were 64 months(3.0-76.3 months), 55 patient achieved complete remission(CR) after 1 cycle of induction chemotherapy(CR rate 67.1%), 25 patients relapsed(30.5%) mainly in very early and early relapse phases, significantly different from the low-risk group (P=0.013), 27 pateitns died(32.9%). The 5-year pEFS and pOS were 57.20% and 58.5%, respectively. Phor BCR/ABLand MRD>10on the 33rd day in the high-risk group were 2 main factors influencing EFS and OS according to single factor analysis. Phor BCR/ABLwas an independent prognostic factor, however, the MRD value on the 33rd day was not statistically significant differente by virtue of COX regression analysis.

CONCLUSIONThe clinical feature of children with ALL in high risk group display low induction CR rate, high recurrence rate and the lower 5-year pEFS. Phor BCR/ABLis regarded as an independent factor of poor prognosis.

OBJECTIVETo study the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA).

METHODSA total of 11 children with SAA were treated with HLA matched siblings (n = 7), umbilical cord blood (n = 2) and haploidentical HSCT (n = 2).

RESULTSAmong 11 children patients, 10 patients achieved engraftment, but 3 children patients experienced secondary graft failure, after donor lymphocyte infusions (DLI), they achieved engraftment again. One patient received cord blood transplantation and experienced primary graft rejection, but acquired autologous recovery. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (10-19 days) in the 9 children received bone marrow or bone marrow and peripheral blood allo-HSCT, while the median time for platelets to reach over 20 × 10(9)/L was 17 days (8-42 days). For the patient received double cord blood transplantation, the time of neutrophile and platelet level recovery was 16 days and 41 days, respectively.

CONCLUSIONIf HLA-matched sibling donor is available, allo-HSCT can be recommended as the first line of treatment for children with SAA. It is feasible for children with SAA to receive allo-HSCT from selective donor, including cord blood and haploidentical HSCT. Donor lymphocyte infusions can improve engraftment.

Allografts ; Anemia, Aplastic ; Child ; Graft Rejection ; Hematopoietic Stem Cell Transplantation ; Humans ; Siblings ; Tissue Donors

OBJECTIVETo investigate thiopurine S-methyltransferase (TPMT) activity and gene promoter polymorphism to probe its significance of individual chemotherapy in acute lymphoblastic leukemia (ALL) children.

METHODSHPLC method was carried out to determine TPMT activity (n=100), which activity at newly diagnosed. At the same time determination of TPMT activity in healthy children (n=180), these children come from the health care clinic. Using online primer3 software design primers, PCR products were purified. To sequence TPMT gene of the patients with clinical events(n=30). According to the method to analysis of correlation between TPMT activity and toxicity.

RESULTSThe average TPMT activities were (31.72±10.31) nmol·g⁻¹Hb·h⁻¹ and (30.70±9.67) nmol·g⁻¹Hb·h⁻¹ in ALL and healthy groups respectively, without gender differences of TPMT activities (P=0.45) in both groups. The TPMT activity with clinical events in newly diagnosed ALL patients (n=30) was (24.07±11.43) nmol·g⁻¹Hb·h⁻¹. There are significant differences of TPMT activities between severe bone marrow suppression [(20.96±7.24) nmol·g⁻¹Hb·h⁻¹] and ALL patients with clinical events groups (P<0.05). The TPMT activity of (40.46±8.18) nmol·g⁻¹Hb·h⁻¹ in recurrence children was also significantly different (P<0.05). TPMT activity in severe liver toxicity group was not significantly different (P=0. 930). Of TPMT gene sequencing in ALL patients with clinical events, only 3 children were heterozygosity mutations of TPMT*3C, while others homozygous genotype. There were significant differences of TPMT activities between heterozygosity genotype [(11.99±1.32) nmol·g⁻¹Hb·h⁻¹] and homozygous genotype groups [(24.95±11.32) nmol·g⁻¹Hb·h⁻¹] (P<0.05). There were five kinds of variations at the vicinity of the promoter region of -100 of tandem repeats (VNTR) polymorphism（*V3/*V3、*V3/*V4、*V4/*V4、*V5/*V5、*V4/*V6）without significant differences of TPMT activities among five kinds (P=0.186).

CONCLUSIONTPMT activity was related to the gene polymorphism. TPMT activity determination had prognostic value and guided individualized treatment.

Child ; Child, Preschool ; Female ; Humans ; Male ; Methyltransferases ; genetics ; Mutation ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prognosis ; Promoter Regions, Genetic

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

OBJECTIVETo investigate the methylation, expression and clinical significance of miR-203 in pediatric acute leukemia.

METHODSThe methylation status of miR-203 promoter CpG islands was detected with methylation-specific polymerase chain reaction. The expression of miR-203 was detected by Taqman real- time quantitative polymerase chain reaction. And the clinical significance of miR-203 in pediatric acute leukemia (ALL) was also analyzed.

RESULTSThe promoter of miR-203 was unmethylated in all of 31 pediatric acute lymphoblastic leukemia, all of 15 pediatric acute myeloid leukemia (AML) and all of 23 controls. The relative expression levels of miR-203 in controls, pediatric acute leukemia, ALL and AML were 16.93±6.31, 48.97±10.38, 55.88±12.91, 24.28±9.10 respectively. The results indicated that miR-203 was significantly up- regulated in pediatric acute leukemia (P=0.011) and ALL (P=0.009), not in pediatric AML (P=0.514) compared with control. The expression of miR-203 was significantly related with the gender, immunophenotype, chromosome, fusion gene, BCR-ABL, SIL-TAL1 and prednisone experiment in pediatric ALL and the gender, chromosome, fusion gene, SIL-TAL1 in pediatric acute leukemia (P<0.05). And in risk stratification pairwise comparisons, the expression of miR-203 in the medium-risk and high-risk groups appeared significantly different (P=0.022).

CONCLUSIONmiR-203 may not be regulated with methylation mechanism in pediatric acute leukemia. miR- 203 may be a protooncogene involved in the formation of pediatric acute leukemia and ALL. Further analyses indicated that high expression of miR-203 may be associated with poor prognosis of pediatric ALL and acute leukemia.

Acute Disease ; Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; CpG Islands ; DNA Methylation ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Infant ; Leukemia ; Leukemia, Myeloid ; genetics ; metabolism ; Male ; MicroRNAs ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Promoter Regions, Genetic

Objective To explore the relationship between the expression of platelet membrane glycoprotein in pediatric idiopathic thrombocytopenic purpura (ITP) and its clinical significance.Methods A modified monoclonal antibody immobilization of platelet antigen (MAIPA) method was used to detect the positive expression rates of 4 platelet membrane glycoproteins (GP Ⅰ b/Ⅸ,GP Ⅰ b,GP Ⅲ a,and GP Ⅰ b) in 80 pediatric patients with ITP.The correlation was explored between the GP positive rate and the clinical efficacy in pediatric ITP.Trying to observe the correlationship between the GP positive rate of pediatric ITP in the total,the different gender,the acute and chronic and the treatment response rate in pediatric ITP respectively.Results There was a significant difference in curative rate statistically between the GP positive group and the GP negative group(x2 =8.535,P ＜ 0.01) in 80 pediatric ITP patients,but no statistic difference in curative rate existed between the 36 female and 44 male(x2 =0.013,P ＞0.05).Markedly statistic difference was found in the female(x2 =4.433,P ＜ 0.05),the same to the male (x2 =4.156,P ＜ 0.05).Meanwhile,there was an extremely statistic difference between 67 acute and 13 chronic patients(x2 =23.513,P ＜ 0.001).Apparently statistic difference also occurred in the acute (x2 =4.157,P ＜ 0.05),but not in the chronic cases (x2 =0.410,P ＞ 0.05).Conclusions The clinical response rate is significantly correlated with the GP positive rate in pediatric ITP,but not correlated with gender.The GP positive rate can reflect the disease status of pediatric ITP to a certain extent and be used as an indicator for judging the efficacy and monitor prognosis of pediatric ITP.

This study was aimed to explore the clinical significance of monitoring level of minimal residual disease (MRD) at different time point in B-lineage childhood acute lymphoblastic leukemia (B-ALL). Two hundred and six children with B-ALL were enrolled in this study from Augest 2008 to September 2011 in our hospital. MRD levels were detected by flow cytometry at day 15, 33 and week 12 after initial chemotherapy. The event-free survival (EFS) for patients based on MRD levels measured at different stages of chemotherapy were compared by Kaplan Meier analyses. The results showed that out of 206 cases 196 cases achieved complete remission (CR) after induction therapy (CR rate 95.1%), the 1- and 3-year EFS rate were (92.7 ± 1.8)% and (78.7 ± 3.7)%, respectively, and the 3-year EFS rate was (85.6 ± 4.9)% in standard risk group, (82.1 ± 5.8)% in intermediate risk group and (58.1 ± 9.2)% in high risk group, there was significant statistical difference between above mentioned 3 groups (P < 0.001). The MRD analysis at different time points showed that the higher the MRD level, the lower the 3-year EFS rate of children with ALL, in which the 3-year EFS rate of MRD ≥ 10(-2) at day 15, MRD ≥ 10(-3) at day 33 and MRD ≥ 10(-3) at week 12 were significantly lower. The MRD ≥ 10(-3) at week 12 was proven to be an independent predictor by multivariate Cox proportional-hazards regression model. The 3-year EFS rate for patients with MRD < 10(-3) and MRD ≥ 10(-3) at week 12 were (86.3 ± 4.1)% vs (55.8 ± 9.1)% (P < 0.05); 8 relapsed among 98 cases with negative MRD (MRD < 10(-4)) at day 33, 19 relapsed among 108 cases with positive MRD at day 33 between the two groups for recurrence rate has significant difference (P < 0.05). It is concluded that dynamically monitoring MRD by multi-parameter flow cytometry can precisely evaluate treatment response, judge treatment outcome and predict relapse in childhood B-ALL. The MRD 10(-2) at day 15, MRD 10(-3) at day 33 and MRD 10(-3) at week 12 should be considered as the best cut-off. MRD ≥ 10(-3) at week 12 was proven to be an independent factor of poor prognosis.
Child ; Child, Preschool ; Female ; Flow Cytometry ; methods ; Humans ; Infant ; Male ; Neoplasm, Residual ; diagnosis ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; therapy ; Prognosis ; Retrospective Studies