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Objective: Cytogenetic abnormalities have been proven to be the most valuable parameter for risk stratification of childhood acute lymphoblastic leukemia (ALL). However, studies on the prevalence of cytogenetic abnormalities and their correlation to clinical features in Chinese pediatric patients are limited, especially large-scale studies., Methods: We collected the cytogenetics and clinical data of 1541 children newly diagnosed with ALL between 2001 and 2014 in four Chinese hospitals, and retrospectively analyzed their clinical features, prognosis and risk factors associated with pediatric ALL., Results: All of these patients had karyotyping results, and some of them were tested for fusion genes by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction. Overall, 930 cases (60.4%) had abnormal cytogenetics in this study, mainly including high hyperdiploidy (HHD, n=276, 17.9%), hypodiploidy (n=74, 4.8%), t(12;21)/TEL-AML1 (n=260, 16.9%), t(1;19)/E2A-PBX1 (n=72, 4.7%), t(9;22)/BCR-ABL (n=64, 4.2%), and t(v;11q23)/MLL rearrangements (n=40, 2.6%). The distribution of each cytogenetic abnormality was correlated with gender, age, white blood cell count at diagnosis, and immunophenotype. In addition, multivariate analysis suggested that t(v;11q23)/MLL rearrangements (OR: 2.317, 95%CI: 1.219-3.748, P=0.008) and t(9;22)/BCR-ABL (OR: 2.519, 95%CI: 1.59-3.992, P<0.001) were independent risk factors for a lower event-free survival (EFS) rate in children with ALL, while HHD (OR: 0.638, 95%CI: 0.455-0.894, P=0.009) and t(12;21)/TEL-AML1 (OR: 0.486, 95%CI: 0.333-0.707, P<0.001) were independent factors of a favorable EFS., Conclusion: The cytogenetic characteristics presented in our study resembled other research groups, emphasizing the important role of cytogenetic and molecular genetic classification in ALL, especially in B-ALL., (© 2021. Huazhong University of Science and Technology.)

Objective: To analyze the outcomes of the children suffered from philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) treated with tyrosine kinase inhibitor (TKI) plus chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: 21 cases of firstly diagnosed Ph + ALL patients aged <12 year treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL 2008) protocol form January 2008 and April 2015 were retrospectively analyzed．The patients were divided into two groups, one group was TKI+ chemotherapy group, the other group was allo-HSCT group., Results: Among 21 patients, 17 were male and 4 were female with a median age of 8 years old (range, 4-12 years), the median follow-up time was 30 moths (range, 10-133 months). All the patients were treated with chemotherapy induced by the high-risk project of CCLG-ALL 2008. Among 14 patients treated with TKI plus chemotherapy, nine patients achieved complete remission. During 3 months after treatment, patients without complete molecular response or with the second complete remission and intensity desire of transplantation were treated with allo-HSCT, among 9 patients with allo-HSCT, six patients achieved long term survival., Conclusion: At TKI era, TKI combined with strong chemotherapy can make Ph + ALL children achieve 5 years event-free survival as campared those treated with allo-HSCT. However, for the patients without complete molecular response persistently and relapsed they can still benefit from allo-HSCT.

Objective: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1 + ALL, and to investigate the prognosis value of these 2 methods., Methods: 55 cases of paediatric TCF3-PBX1 + ALL patients from April 2008 to April 2015 were enrolled and analyzed. The FCM and PCR was used to detect the MRD in 239 bone marrow samples of 55 patients. All statistical analyses were carried out by using SPSS software version 16., Results: Among the 55 children with TCF3-PBX1 + ALL, there were 30 male and 25 female. The median age was 5 (1-14) years. 20 patients relapsed during follow-up. The MRD results from PCR and FCM showed a strong correlation between both methods (K=0.774, P<0.001). There was no significant difference in 5-years DFS and OS between the patients in PCR + and PCR - groups on day 15 or day 33. The 5 year DFS rate between the patients in FCM - and FCM + was 63.9%±7.0% and 0; the 5 year OS rate was 66.5%±7.9% and 0. Combined with the result of FCM and PCR, at the d 33 of treatment, the 5-year DFS rate in FCM - /PCR - and single positive group was 65.4%±7.2% and 25.0%±15.3% (P<0.01)., Conclusion: The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.

Objective: To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL)., Methods: A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups., Results: A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P<0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P>0.05)., Conclusions: The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.

Objective: To study the long-term efficacy of CCLG-ALL2008 protocol used for treatment of childhood acute lymphoblastic leukemia (ALL)., Methods: Nine hundred and forty children with newly diagnosed ALL from January 2008 to April 2015 were treated with CCLG-ALL2008 protocol. Overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Cox proportional hazards model was used for analyses of prognostic factors., Results: Among the 940 newly diagnosed ALL patients, 570 patients were male, and 370 patients were female, the median age of onset was 5 years old (from 1 to 15 years old). The complete reaction rate (CR) was 96.7%. Survival analysis of 916 ALL patients with CR estimated by follow up [ (median follow up period 64 months (from 3 to 123 months) ] showed that, the expected 10 year OS rate was (78.6±1.5)% and the EFS rate was (66.0±1.8)%. The long-term OS rate of standard risk, intermediate risk and high risk patients was (93.0±1.5)%, (77.6±2.7)%, and (59.3±3.7)%, respectively, and the long-term EFS rate in standard risk, intermediate risk and high risk patients was (84.2±2.2)%. (67.8±2.9)%, and (42.1±3.9)% respectively. 10 year OS rate in B-ALL patients (79.8±1.6)% was significantly higher than that in T-ALL patients (53.5±6.3)% (P＜0.01). Among of all the patients, patients 201 (21.9%) relapsed, the median relapse time was 19 months (from 2 months to 81 months). The 10 year EFS rate was (81.7±3.7）% in the patients with MRD rate ＜0.01% after induction therapy, which was significantly higher than that in the patients with MRD rate＞0.01% (48.4±9.8)%., Conclusion: The therapeutic efficacy of the CCLG-ALL2008 protocol is closed to the level of supior study group in the world. Risk stratification can improve the outcome for childhood ALL. Immunophenotyping shows the outcome of B-ALL is better than that of T-ALL. MRD negative patients after induction therapy shows better prognosis compared with that of MRD positive patients.

Objective: To study the clinical features of central nervous system infiltration-positive (CNSI+) children with acute lymphoblastic leukemia (ALL) based on flow cytometry, as well as the association of such clinical features with prognosis., Methods: A retrospective analysis was performed for the clinical data of 66 CNSI+ children with ALL treated from April 2008 to June 2013. Clinical features, laboratory examination results and prognosis were compared between the children in different chemotherapy stages (induction stage and consolidation/maintenance stage)., Results: Among the 66 CNSI+ children, 50 were in the induction stage and 16 in the consolidation/maintenance stage. Compared with the CNSI+ children in the induction stage, the CNSI+ children in the consolidation/maintenance stage had a significantly higher proportion of children with the genes associated with good prognosis based on the results of molecular biology (P<0.05), as well as a significantly higher recurrence rate (P<0.05). Recurrence was observed in 21 CNSI+ ALL children, among whom 10 were in the induction stage and 11 were in the consolidation/maintenance stage. Compared with the children experiencing recurrence in the induction stage, the children experiencing recurrence in the consolidation/maintenance stage had a significantly higher proportion of children with recurrence of the central nervous system and bone marrow (P<0.05), as well as significantly higher proportion of biochemical positive rate of cerebrospinal fluid (P<0.05). The children in the induction stage had a significantly higher recurrence-free survival rate than those in the consolidation/maintenance stage (P<0.001), while there was no significant difference in overall survival rate between the two groups (P>0.05)., Conclusions: In children with ALL, CNSI+ has a marked effect on recurrence-free survival rate in different chemotherapy stages, but has no obvious effect on overall survival rate. CNSI+ patients in the consolidation/maintenance stage have a higher recurrence.

Objective: To analyze the therapeutic outcomes of acute lymphoblastic leukemia(ALL) patients with MLL gene rearrangement., Methods: Clinical outcomes of 28 ALL patients aged less than 12 years old with MLL gene rearrangement treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG -ALL 2008) protocol from January 2008 to April 2015 were retrospectively analyzed., Results: Among 28 patients, 14 were boys and 14 were girls, median age was 36(4-144) months and median follow-up period was 12.5 (ranged 2-106) months, and 10 were infants. All patients were given induction chemotherapy and the high-risk project of CCLG-ALL 2008. At the last time of follow-up, five patients gave up and were loss to follow-up. The 5 years OS and EFS were 52.2% and 47.8% respectively for the other 23 patients. The 5 years OS and EFS(28.6% and, 88.9%), (P=0.012), (28.6%, 77.8%), (P=0.048) rate of WBC≥50×10 9 /L and ＜50×10 9 /L groups at first vistit showed a significantly different. Patients with good response to predisone, less than 12 months， sex， CD10- showed low trend of 5 years OS and EFS, however there was no statistical difference (P＞0.05)., Conclusion: The 5 years OS is 52.2% and 5 years EFS is 47.8% for those ALL patients with MLL gene rearrangement. The WBC≥50×10 9 /L at first visit is adverse prognostic factor.

Objective: To study the short-term effect of two different re-induction regimens in the treatment of acute lymphoblastic leukemia (ALL) children with bone marrow recurrence., Methods: A retrospective analysis was performed for 57 ALL children with bone marrow recurrence. According to their treatment regimen, they were divided into two groups: VMDP (vincristine + mitoxantrone + dexamethasone + PEG-asparaginase; n=42) and VIDP (vincristine + idarubicin + dexamethasone + PEG-asparaginase; n=15). The two groups were compared in terms of complete response rate and incidence rate of adverse reactions., Results: There was no significant difference in complete response rate between the VMDP and VIDP groups (74% vs 73%, P>0.05). All children experienced grade ≥3 hematological adverse events. The VMDP group had a significantly lower chemotherapy-related mortality rate than the VIDP group (P<0.05). There was no significant difference in the incidence rate of infection between the two groups (P>0.05)., Conclusions: For ALL children with bone marrow recurrence, both re-induction regimens can achieve a relatively high complete response rate, and VMDP regimen has a lower chemotherapy-related mortality rate and can thus be used as an option for re-induction in ALL children with bone marrow recurrence.

Objective: To study the long-term clinical effect of the CCLG-ALL2008 regimen in the treatment of children newly diagnosed with acute lymphoblastic leukemia (ALL) with different molecular biological features., Methods: A total of 940 children who were newly diagnosed with ALL were enrolled in this study. The children were treated with the CCLG-ALL2008 regimen. A retrospective analysis was performed for the long-term outcome of ALL children with different molecular biological features., Results: Among the 940 children with ALL, there were 570 boys and 370 girls, with a median age of onset of 5 years (range 1-15 years) and a median follow-up time of 65 months (range 3-123 months). The complete response (CR) rate was 96.7%, the predicted 10-year overall survival (OS) rate was 76.5%±1.5%, and the event-free survival (EFS) rate was 62.6%±3.0%. After CR was achieved after treatment, the overall recurrence rate was 21.9%. The children with positive ETV6-RUNX1 had the lowest recurrence rate and were prone to late recurrence, and those with positive MLL rearrangement had the highest recurrence rate and were prone to early recurrence. The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year OS rate than those with positive TCF3-PBX1, BCR-ABL, or MLL rearrangement and those without molecular biological features (P<0.05). The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year EFS rate than those with positive BCR-ABL or MLL rearrangement (P<0.05)., Conclusions: Molecular biological features may affect the long-term prognosis of children with ALL, and positive MLL rearrangement and BCR-ABL fusion gene are indicators of poor prognosis. Children with positive ETV6-RUNX1 fusion gene have the highest long-term survival rate.

Objective: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL)., Methods: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×10 9 /L; n=629). The thrombocytopenia group was further divided into (50- <100)×10 9 /L (n=243), (20- <50)×10 9 /L (n=263), and <20×10 9 /L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed., Results: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×10 9 /L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×10 9 /L subgroup, and the (20- <50)×10 9 /L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×10 9 /L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×10 9 /L subgroup, and the (20- <50)×10 9 /L subgroup (P<0.05)., Conclusions: ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×10 9 /L have the worst prognosis.

Objective: To investigate the application of multiplex ligation-dependent probe amplification (MLPA) in the detection of copy number variations (CNVs) in pediatric ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL), to compare this method with conventional karyotype analysis and fluorescence in situ hybridization (FISH), and to evaluate the value of MLPA., Methods: The clinical data of 95 children with ETV6/RUNX1-positive ALL who were treated from January 2006 to November 2012 were analyzed retrospectively, including clinical features, results of karyotype analysis, and results of FISH. CNVs were detected with MLPA., Results: CNVs were detected in 73 (77%), and the median number of CNVs was 1 (range 0-6). The CNVs of EBF1, CDKN2A/2B, PAX5, ETV6, RB1, and BTG1 were detected in more than 10% of all the patients. The changes in the chromosome segments carrying the genes with CNVs detected by MLPA were not detected by conventional karyotype analysis. The coincidence rate between the CNVs in ETV6 gene detected by FISH and those detected by MLPA was 66%., Conclusions: MLPA is an efficient and convenient method to detect CNVs in children with ETV6/RUNX1-positive ALL.

Objective: To 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., Methods: The 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)., Results: The 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., Conclusions: Application of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.

Objective: To study the clinical features of children with relapsed acute lymphoblastic leukemia (ALL) treated with the CCLG-ALL2008 protocol., Methods: The data of 591 children who were newly diagnosed with ALL and were treated with the CCLG-ALL 2008 protocol between April 2008 and June 2013 were collected, and the clinical features of 80 children with relapsed ALL were retrospectively analyzed., Results: After treatment with the CCLG-ALL2008 protocol, the recurrence rate in the standard-risk, intermediate-risk and the high-risk groups were 7.0%, 10.7% and 28.7% respectively (P<0.05). The recurrence rate in patients with TEL/AML1-positive ALL was 8.0%, and the 5-year overall survival (OS) of the relapsed patients was 37.04%. The recurrence rates in patients with MLL-positive and BCR/ABL-positive ALL were 35.0% and 24.2% respectively, and none of the relapsed patients had long-term survival. The recurrence mainly occurred at the very early stage (53%), and none of patients with recurrence at the very early stage had long-term survival. The recurrence occurred at early stage and late stage accounted for 34% and 14% respectively, and the 5-year OS rates of patients with recurrence at early stage and late stage were 11.44% and 60.00% respectively. The sites of recurrence were mainly bone marrow alone (83%), and the 5-year OS of patients with recurrence at bone marrow alone was 9.23%. The recurrence in bone marrow and outside bone marrow accounted for 11%, and the 5-year OS of patients with recurrence in both bone marrow and outside bone marrow was 25.00%. The recurrence only outside bone marrow accounted for 6%, and the 5-year OS of patients with recurrence only outside bone marrow was 100%. The recurrence rate in patients with T-cell ALL was 9.5%, and none of the relapsed patients had long-term survival. The recurrence rate in patients with B-cell ALL was 14.3%, and the 5-year OS of the relapsed patients was 15.52%., Conclusions: After treatment with the CCLG-ALL2008 protocol, a relatively high recurrence rate is observed in children with high-risk ALL. Positive MLL and positive BCR/ABL are high-risk factors for recurrence. The recurrence rate is not significantly correlated with immunophenotype. A very low survival rate is seen in children whose recurrence have the following features: at early stage, only in bone marrow, T-cell ALL, and abnormal BCR/ABL and MLL.

Objective: To study the long-term efficacy of CAMSBDH-ALL chemotherapy protocol for the treatment of childhood acute lymphoblastic leukemia (ALL)., Methods: Three hundred and eighteen children who were newly diagnosed with ALL between January 1999 and December 2007 were enrolled in this study. Among the 318 children, 83 children who hospitalized before December 2002 were treated with CAMSBDH-ALL99 protocol, including 48 patients of standard risk and 35 patients of high risk. The patients (n=235; 131 in standard risk and 104 in high risk) who hospitalized after December 2002 were treated with CAMSBDH-ALL03 protocol. Patients in the CAMSBDH-ALL99 protocol group were treated with conventional chemotherapy. CAMSBDH-ALL03 protocol was modified based on the CAMSBDH-ALL99 protocol., Results: The long-term overall survival (OS) and event-free-survival (EFS) in the CAMSBDH-ALL03 group was significantly higher than in the CAMSBDH-ALL99 (P&lt;0.01). The long-term OS and EFS of standard risk and high risk patients in the CAMSBDH-ALL03 protocol group were significantly higher than in the CAMSBDH-ALL99 protocol group (P&lt;0.01). The CAMSBDH-ALL03 protocol group showed a significantly lower recurrence rate (28.9%) than in the CAMSBDH-ALL99 protocol group (50.6%) (P&lt;0.05). The mortality rate in the CAMSBDH-ALL03 protocol group was 28.5% vs 56.6% in the CAMSBDH-ALL99 protocol group (P&lt;0.05)., Conclusions: The therapeutic effect of the CAMSBDH-ALL03 protocol is supior to the CAMSBDH-ALL99 protocol group for childhood ALL, with a higher long-term survival rate.

Objective: To investigate the potential influence of granulocyte-colony stimulating factor (G-CSF) on the prognosis of patients with acute leukemia(AL)., Methods: In 171 evaluable cases with AL, the complete remission (CR) rate post first course of chemotherapy, CR rate, effective rate, duration of leucopenia post chemotherapy, CR duration, lifespan and the relationship between the dosage of G-CSF and CR duration or lifespan were retrospectively analyzed with Chi-square test, paired t-test, Cox regression, Kaplan-Meier and rank correlation method. For remission induction and postremission therapy, the cases with acute myeloid leukemia (AML) received chemotherapy regimes based on daunorubicin + ara-C (DA), homoharringtonine + ara-C (HA) or mitoxantrone + ara-C (MA). The patients with acute lymphocyte leukemia (ALL) were treated with regimes based on vinblastine + daunorubicin + prednisone (VDP), vinblastine + adriamycin + prednisone (VAP), vinblastine + mitoxantrone + prednisone (VMP) or cyclophosphamide + vinblastine + daunorubicin + prednisone(CODP). In G-CSF group, the patients whose WBC count fell below 1.0 x 10(9)/L after chemotherapy were given rhG-CSF (1.5-6.0 microg.kg(-1).d(-1)) until WBC count restored to 2.5 x 10(9)/L., Results: (1) Patients administered applied with G-CSF had shorter duration of leucopenia. However, there was no statistical difference between the two groups in the CR rate post first course of chemotherapy, CR rate and the effective rate of treatment. (2) Use of G-CSF did not affect CR durations of ALL patients, but shortened that of AML patients. (3) The application of G-CSF had little effect on the lifespan of ALL patients. By contrast, it showed clearly negative effects on that of AML patients. (4) No relationship between the dosage of G-CSF and CR duration or lifespan in AML patients., Conclusion: With AML patients, the administration of G-CSF must be very cautious.