The prognostic effect on childhood acute lymphoblastic leukemia of CD34+CD38- expressed in leukemia cells.

OBJECTIVE: Acute lymphoblastic leukemia is the most common malignant disease in children. CD34 and CD38 are expressed in both normal and leukemia cells, but studies of their prognostic associations in childhood acute lymphoblastic leukemia are limited. The aim of this study was to investigate the prognostic effect of CD34 + CD38- leukemia cells in this childhood cancer. METHODS: From January 2014 to January 2019, children with newly diagnosed acute lymphoblastic leukemia were included in this study and followed up until July 2020. The participants were divided into CD34+ and CD34- groups according to CD34 expression level at diagnosis, and the CD34+ group was further divided into CD34 + CD38- and CD34 + CD38+ subgroups based on CD38 expression level. We tracked clinical biological features, therapeutic outcomes, and other patient data for comparisons. RESULTS: The OS and EFS did not differ significantly between the CD34+ and CD34- groups (both P > 0.05). CD34+CD38- group and CD34+CD38+ group were further compared. OS differed significantly between these two groups (χ2 = 3.89, P = 0.048), as did the recurrence rate (χ2 = 5.04, P = 0.025), but EFS did not (χ2 = 1.45, P > 0.05). Survival analysis in patients with recurrence showed a significantly higher OS for the CD34 + CD38+ group compared with the CD34 + CD38- group (χ2 = 5.08, P = 0.024). The CD34+CD38- group and CD34+CD38+ group were matched for propensity scores. When recurrence was compared in the two groups after matching, the difference was statistically significant (P < 0.001). CONCLUSION: CD34+ and CD34- expression does not differ by prognosis in children with acute lymphoblastic leukemia, but CD34 + CD38- may indicate a poor prognosis.

Risk Factors for Relapse of Childhood B Cell Acute Lymphoblastic Leukemia.

BACKGROUND B cell acute lymphoblastic leukemia (B-ALL) is the most common type of ALL. This study aimed to explore risk factors for relapse of childhood B-ALL. MATERIAL AND METHODS Total of 102 pediatric B-ALL patients were included in this study. B-ALL patients were divided into a relapse group and a non-relapse group. Chemotherapy-induced agranulocytosis time, fusion gene, and minimal residual disease (MRD) were assessed. White blood cell (WBC) count in peripheral blood and risk stratification were evaluated in newly-diagnosed patients. Kaplan-Meier plots were used to evaluate the correlation between risk factors and relapse rates. Multivariate analysis was performed with Cox proportional hazard model to estimate relative risk (RR), 95% confidence interval (95% CI), and hazard ratio (HR). Finally, 99 cases of B-ALL were included in this study. RESULTS There were significant differences between the relapse group and the non-relapse group in age (p=0.004), chemotherapy-induced agranulocytopenia (p=0.001), WBC count in peripheral blood of newly diagnosed patients (p=0.016), risk stratification (p=0.000), and MRD at 12th week (p=0.007). Age over 10 years, high-risk stratification, long period of agranulocytopenia, higher WBC counts, and MRD more than 10⁻4 were correlated with higher B-ALL relapse rate (p<0.05). Multivariate analysis showed significantly higher relapse rates for age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻4, with RR (95% CI) of 4.001 (1.005-15.930), 4.964 (1.050-23.456), and 4.646 (1.383-15.614), respectively. CONCLUSIONS Agranulocytopenia ≤7 days, peripheral blood WBC >100×109/L, and MRD at 33rd day >10⁻4 were associated with B-ALL relapse. Age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻4 were independent risk factors for relapse.

[Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis].

OBJECTIVE: To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. METHODS: Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. RESULTS: The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). CONCLUSION: The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

[Expression of Wif-1 and ß-catenin in the Wnt pathway in childhood acute lympho-blastic leukemia].

OBJECTIVE: To investigate the expression and possible roles of Wnt inhibitory factor-1 (Wif-1) and ß-catenin in the Wnt pathway in childhood acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 35 children who had newly-diagnosed ALL and achieved complete remission on day 33 of remission induction therapy were retrospectively reviewed. The children before treatment were considered as the incipient group, and those who achieved complete remission on day 33 were considered as the remission group. Fifteen children with non-malignant hematologic diseases were enrolled as the control group. RT-PCR was used to measure the mRNA expression of Wif-1 and ß-catenin. ELISA was used to measure the protein expression of Wif-1. RESULTS: Compared with the control and remission groups, the incipient group had significantly lower mRNA and protein expression of Wif-1 and significantly higher mRNA expression of ß-catenin (P<0.05). In the incipient and remission groups, high-risk children showed significantly higher mRNA expression of ß-catenin and significantly lower mRNA and protein expression of Wif-1 than the medium- and low-risk children (P<0.05). In the incipient and remission group, the children with T-cell acute lymphoblastic leukemia showed significantly higher mRNA expression of ß-catenin and significantly lower mRNA and protein expression of Wif-1 compared with those with B-lineage acute lymphoblastic leukemia (P<0.05). In each group, there was a negative correlation between the mRNA expression of Wif-1 and ß-catenin (P<0.05). CONCLUSIONS: Reduced expression of Wif-1 and increased expression of ß-catenin may be involved in the pathogenesis of childhood ALL, and the degree of reduction in Wif-1 and/or increase in ß-catenin may be related to prognosis.