Prognostic Significance of CD20 Expression in Children with Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

INTRODUCTION: The prognostic significance of CD20 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unclear. Therefore, in this study, we evaluated the prognostic value of CD20 expression in leukemia blasts in pediatric BCP-ALL at our institute. METHODS: Between 2005 and 2017, 796 children with newly diagnosed Philadelphia-negative BCP-ALL were enrolled consecutively; clinical characteristics and treatment outcomes were analyzed and compared between CD20-positive and CD20-negative groups. RESULTS: CD20 positivity was observed in 22.7% of enrolled patients. The analysis of overall and event-free survival showed that white blood cell count ≥50 × 109/L, no ETV6-RUNX1, day 33 minimal residual disease (MRD) ≥0.1%, and week 12 MRD ≥0.01% were independent risk factors. Meanwhile, in the CD20-positive group, week 12 MRD ≥0.01% was the only factor associated with long-term survival. Moreover, subgroup analysis revealed that in patients with extramedullary involvement (p = 0.047), MRD ≥0.1% on day 33 (p = 0.032), or MRD ≥0.01% at week 12 (p = 0.004), CD20 expression led to a poorer outcome compared to those without CD20 expression. CONCLUSIONS: Pediatric BCP-ALL with CD20 expression had unique clinicopathological characteristics, and MRD remained the major prognostic factor. CD20 expression had no prognostic value in pediatric BCP-ALL.

Low EVI1 expression at diagnosis predicted poor outcomes in pediatric Ph-negative B cell precursor acute lymphoblastic leukemia patients.

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068-136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818 .

[Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene]. / 表达PRAMEåŸºå› çš„å„¿ç«¥æ€¥æ€§Bæ·‹å·´ç»†èƒžç™½è¡€ç— çš„ä¸´åºŠç‰¹ç‚¹åŠé¢„åŽåˆ†æž.

OBJECTIVES: To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors. RESULTS: Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS: Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.

Superior survival of unmanipulated haploidentical haematopoietic stem cell transplantation compared with intensive chemotherapy as post-remission treatment for children with very high-risk philadelphia chromosome negative B-cell acute lymphoblastic leukaemia in first complete remission.

We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow-up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.

Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t(8;21) acute myeloid leukemia in first remission based on MRD-guided treatment.

BACKGROUND: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. METHODS: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed. RESULTS: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009). CONCLUSIONS: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.

[Clinical characteristics and prognostic analysis of pediatric pro-B cell acute lymphoblastic leukemia].

OBJECTIVE: To explore the clinical-biological characteristics and prognosis of pediatric pro-B cell acute lymphoblastic leukemia (pro-B-ALL). METHODS: A total of 64 patients aged less than 18 years old with pro-BALL were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. RESULTS: Pro-B-ALL occurred in 6.23% (64/1 028) of pediatric ALL. Among the 64 patients, 35 were male and 29 were female. The median age was 7.0 years (range 0.4-16.0 years) at diagnosis, of which 39% and 6% were ≥ 10 years old and < 1 year old respectively. The median WBC count was 25.5×109/L[range (0.4-831.9)×109/L], of which 35.9% were ≥ 50×109/L. MLL-r positivity was the most frequent genetic alteration in pro-B ALL, occurring in 34% of patients, with lower frequency of CD22 and CD13 expression and higher frequency of CD7 expression, while lower frequency of CD33 expression was found in patients with MLL-AF4 positivity. At a median follow-up of 60.0 months (range 4.9-165.3 months), the estimated 5-year overall survival (OS) and event-free survival (EFS) in the 64 patients were (85±5)% and (78±5)% respectively. Cox proportional hazards regression analysis identified MRD ≥ 0.1% at 3 months after chemotherapy as an independent adverse prognostic factor for both 5-year OS and EFS. CONCLUSIONS: Pediatric pro-B ALL is a heterogeneous disease with clinical and biological diversity. Biological characteristics, such as immunological markers, genetic alterations, and MRD at 3 months after chemotherapy may be important factors for the long-term prognosis.

[Influence of dasatinib treatment on body height in children with acute myeloid leukemia].

OBJECTIVE: To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML). METHODS: A retrospective analysis was performed for the clinical data of 86 AML children aged <17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment. RESULTS: There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032). CONCLUSIONS: Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.

Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-Term Survival for High-Risk Pediatric Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Tyrosine Kinase Inhibitor Era.

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in the tyrosine kinase inhibitor (TKI) era is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of Ph+ ALL in the TKI era. We analyzed clinical data of Ph+ ALL patients aged 1 to 18 years who received imatinib added to intensive chemotherapy at the start of induction therapy. Among the 68 patients who completed at least 2 consolidation cycles, 44 underwent transplantation (transplant arm) and 24 received continuous TKI with chemotherapy (nontransplant arm). At the 3-year follow-up the cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 23.5%, 73.4%, and 80.3%, respectively. Multivariate analysis showed that hematologic response (whether complete remission [CR] was achieved) at the induction end, BCR-ABL levels (whether major molecular response [MMR] was achieved) at 3 months, and transplantation were independent affecting factors for CIR, EFS, and OS. In the risk stratification analysis based on the first 2 prognostic factors mentioned above, no significant difference existed between the transplant and nontransplant arms for the probabilities of 3-year OS, EFS, and CIR in the standard-risk group (no poor prognostic factors). Meanwhile, OS, EFS, and CIR rates were significantly better in the transplant arm in the high-risk group (≥1 poor prognostic factor). Among the 44 patients in the transplant arm, 37 underwent haplo-HSCT. Achieving CR at the induction end, MMR at 3 months, and haplo-transplant were also independent favorable factors of CIR, EFS, and OS in the nontransplant and haplo-HSCT arms. Haplo-HSCT showed a significant survival advantage in the high-risk group only. Hematologic response at the induction end and BCR-ABL levels at 3 months are likely to be useful for identifying pediatric Ph+ ALL patients at a high risk of relapse in the TKI era. Children with Ph+ ALL in first CR may benefit from allo-HSCT, particularly those at high risk. Haplo-HSCT could achieve good long-term survival for pediatric Ph+ ALL. Thus, haplo-HSCT can be an alternative approach for high-risk Ph+ ALL patients.

Night Sleep Duration and Risk of Cognitive Impairment in a Chinese Population: A Cross-sectional Study.

OBJECTIVE: Although sleep is one of the most important health-related behavioral factors, the association between night sleep duration and cognitive impairment has not been fully understood. A cross-sectional study was conducted with a random sample of 2,514 participants (⋝ 40 years of age; 46.6% women) in China to examine the association between night sleep duration and cognitive impairment. METHODS: Night sleep duration was categorized as ⋜ 5, 6, 7, 8, or ⋝ 9 h per night. Cognitive function was measured using the Mini-Mental State Examination. A multivariate regression analysis was used to analyze the association of night sleep duration with cognitive impairment. A total of 122 participants were diagnosed with cognitive impairment. RESULTS: A U-shaped association between night sleep duration and cognitive impairment was found. The odds ratios (95% confidence intervals) of cognitive impairment (with 7 h of daily sleep being considered as the reference) for individuals reporting ⋜ 5, 6, 8, and ⋝ 9 h were 2.14 (1.20-3.83), 1.13 (0.67-1.89), 1.51 (0.82-2.79), and 5.37 (1.62-17.80), respectively (P ⋜ 0.01). CONCLUSION: Short or long night sleep duration was an important sleep-related factor independently associated with cognitive impairment and may be a useful marker for increased risk of cognitive impairment..

[Clinical characteristics and prognostic analysis of children and adolescents over 10 years of age with acute lymphoblastic leukemia].

OBJECTIVE: To explore the clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). METHODS: A total of 86 newly diagnosed ALL children and adolescents over 10 years of age (62 cases of B-ALL and 24 cases of T-ALL) were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis. RESULTS: Of 86 patients, 62 were in medium risk, and 24 in high risk. At diagnosis, 53 patients (62%) had hepatomegaly, 50 patients (58%) had splenomegaly, and 46 patients (54%) had lymphoadenopathy. Twenty-nine patients (34%) showed high leukocyte counts (≥50×109/L) at diagnosis. The karyotype analysis was performed on 78 patients. The percentage of hyperdiploidy was 19% (15 cases), and that of hypodiploidy was 5% (4 cases). Eleven patients (14%) had abnormalities of chromosome structure. Of them, one patient was Philadelphia chromosome-positive, and another patient had the t (1; 19) chromosomal translocation. Three patients (4%) were positive for TEL/AML1, 3 (4%) were positive for E2A/PBX1, 6 were positive for BCR/ABL (7%), and 4 (5%) were positive for SIL/TAL1. During 4 weeks of induction therapy, 85 patients (99%) achieved complete remission (CR). In 86 patients, the 5-year anticipated EFS and OS were (64±6)% and (75±5)% respectively. The 5-year EFS and OS in the medium risk group were significantly higher than those in the high risk group (P<0.05). The 5-year EFS in B-ALL patients was significantly higher than that in T-ALL patients (P<0.05). COX multivariate analysis showed that white blood counts at diagnosis and minimal residual disease (MRD) after induction therapy were independent prognostic factors. CONCLUSIONS: Children and adolescents with ALL over 10 years of age often have clinical characteristics of unfavorable prognosis. White blood counts at diagnosis and MRD after induction therapy may be important factors for the long-term prognosis.

[Prognostic impact of loss of sex chromosomes in children with acute myeloid leukemia subtype M2].

OBJECTIVE: To study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype. METHODS: According to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups. RESULTS: The 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05). CONCLUSIONS: Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.

[A comparison of minimal residual disease in children with acute lymphoblastic leukemia of different genetic abnormalities].

OBJECTIVE: To study the changes of minimal residual disease (MRD) in children with B cell acute lymphoblastic leukemia (B-ALL) of different genetic abnormalities. METHODS: Between February 2004 and April 2013, 271 newly diagnosed B-ALL pediatric patients who had finished the induction chemotherapy were enrolled in the study. The characteristics of changes in MRD in patients with different genetic abnormalities on the 15th day and at the end of the induction therapy were analyzed. RESULTS: On the 15th day of the induction chemotherapy, the MRD positive proportion in patients with hyperdiploid was higher on all the three cut-off levels of MRD≥0.1%, 1% and 10% compared to patients without hyperdiploid (P<0.05), but there was no significant difference in the MRD positive proportion on the three levels of MRD between the TEL-AML1-positive and TEL-AML1-negative groups (P>0.05). On the end of induction chemotherapy, there was no significant difference in the MRD positive proportion on the three levels of MRD between the patients with and without hyperdiploid (P>0.05), neither between the BCR-ABL-positive and negative groups. The MRD positive proportion in TEL-AML1-negative patients was significantly higher than in TEL-AML1-positive patients on all three levels of MRD (P<0.05). The MRD positive proportion on two levels of MRD≥0.01% and 0.1% in E2A-PBX1-negative patients was significantly higher than in E2A-PBX1-positive patients (P<0.05). CONCLUSIONS: Children with B-ALL of different genetic abnormalities have different MRD levels during, and at the end of, induction therapy. The prognostic significance of MRD may be related to the genetic abnormalities.

CD19-Specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-term Follow-up.

PURPOSE: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. MATERIALS AND METHODS: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. RESULTS: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. CONCLUSION: CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

[Therapeutic effect of clofarabine in children with relapsed or refractory acute lymphoblastic leukemia].

OBJECTIVE: To explore the efficacy and adverse effects of clofarabine for relapsed/refractory acute lymphoblastic leukemia in children. METHODS: Twenty-six pediatric patients with relapsed/refractory acute lymphoblastic leukemia were treated with clofarabine. There were 22 males and 4 females, with a mean age of 9.5 years (ranging from 4 to 17 years). They received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days. Thirteen patients received two cycles and one patient received three cycles. RESULTS: In the first cycle of clofarabine, complete remission was obtained in 11 children (42%) and partial remission was obtained in 7 children (27%). Eight children (31%) were considered unresponsive. In the second cycle, 11 (85%) of the 13 children obtained complete remission, 1 (8%) partial remission and 1 (8%) was unresponsive. One child received three cycles and obtained complete remission in each cycle. The common adverse events were myelosuppression, infection, liver dysfunction and gastrointestinal adverse reactions. There were no chemotherapy-related deaths. CONCLUSIONS: Clofarabine is effective in the treatment of children with relapsed/refractory acute lymphoblastic leukemia and its adverse effects can be tolerated. Clofarabine could be a promising new treatment for relapsed/refractory acute lymphoblastic leukemia.

Clinical Analysis of Pediatric T-Cell Acute Lymphoblastic Leukemia Using the MRD-Oriented Strategy System.

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) has historically been associated with a poor prognosis. However, prognostic indicators and methods of treatment used for T-ALL remain controversial. A total of 136 children newly diagnosed with T-ALL between 2005 and 2018 were consecutively enrolled in this study. We assessed the effect of different prognostic factors, such as clinical characteristics, minimal residual disease (MRD), and the role of transplantation in postremission treatment, as the outcomes. Compared with B-ALL patients, patients with T-ALL are generally older, more likely to be male and have a higher white blood cell count. The complete remission (CR) rate was 95.6%, while the 5-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.3 ± 3.7%, 71.3 ± 3.9%, and 24.4 ± 3.8%, respectively. In the multivariate analysis, day 33 MRD ≥0.1% and hyperleukocytosis were associated with a significantly worse prognosis in the whole group. Transplantation resulted in a significant survival advantage, compared with chemotherapy, for high-risk (HR) patients (5-year CIR: 15.6 ± 10.2% vs. 55.6 ± 11.7%, P = .029). The prognosis of children with T-ALL was poor, and the MRD on day 33 was found to be an important predictive factor of clinical outcome at our center.

[Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1+ B-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis. METHODS: The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed. RESULTS: There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026). CONCLUSION: In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.

Prognostic significance of Wilms' tumor gene 1 expression in children with B-cell precursor acute lymphoblastic leukemia.

Introduction: The prognostic role of Wilms' tumor 1 (WT1) gene expression at diagnosis in children with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is still controversial. Methods: We detected the WT1 transcript levels of 533 de novo pediatric BCP-ALL patients using TaqMan-based real-time quantitative PCR and analyzed their clinical features. Results: The WT1 transcript levels differed among the distinct molecularly defined groups, with the highest levels in the KMT2A rearrangements (KMT2A-r) group. According to the results of the X-tile software, all patients were divided into two groups: WT1/ABL ≥ 0.24% (group A) and <0.24% (group B). The proportions of patients whose age was ≥10 years old, with immunophenotype of Pro-B, belonging in high-risk group, or with minimal residual disease (MRD) ≥ 0.01% at week 12 were significantly higher in group A than in group B. In the B-other group, WT1 overexpression was an independent risk factor of overall survival (OS) rate (P = 0.042), and higher MRD ≥ 0.01% at week 12 was associated with lower OS rate (P<0.001) and event-free survival rate (P<0.001). Moreover, the subgroup analysis revealed that, in patients with initial WBC<50 × 109/L or MRD<0.1% at day 33 or MRD<0.01% at week 12 or in the standard-risk group, WT1 overexpression led to a poorer outcome in comparison with those with WT1 downexpression (P<0.05). Discussion: Therefore, pediatric BCP-ALL with WT1 overexpression had unique clinico-pathological characteristics and poor treatment response. In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.

[Clinical features and etiological spectrum in children with pancytopenia].

OBJECTIVE: To study the clinical features and etiological spectrum of pancytopenia in children. METHODS: The clinical data of 174 children with pancytopenia between September 2003 and January 2010 were retrospectively reviewed. RESULTS: Pale face was the most common clinical manifestation (147 cases, 84.5%), followed by bleeding (87 cases, 50.0%) and fever (41 cases, 23.6%). Mild to moderate anemia, severe thrombocytopenia and mild leucopenia were common in complete blood count. Of the 174 children, pancytopenia was attributed to hematopoietic system diseases in 155 cases (89.1%) and non-hematopoietic system diseases (virus infections, systemic lupus erythematosus, hypersplenism and neuroblastoma) in 6 cases (3.4%). Aplastic anemia (91 cases, 52.3%) was the most common cause of pancytopenia, followed by myelodysplastic syndrome (37 cases, 21.3%), acute leukemia and other hematological tumours (11 cases, 6.3%) and hemophagocytic syndrome (6 cases, 3.4%). The cause of pancytopenia was not identified in 13 cases (7.5%). CONCLUSIONS: Anemia, bleeding and fever are the main clinical manifestations of pancytopenia in children. Pancytopenia is mostly caused by aplastic anemia in children. Myelodysplastic syndrome, hematological tumours and hemophagocytic syndrome are also the common causes.

[Clinical features and prognosis of t (8; 21)/AML1-ETO-positive childhood acute myeloid leukemia].

UNLABELLED: OBJECTIVE To study the clinical and biological characteristics and prognosis of t(8;21)/AML1-ETO-positive childhood acute myeloid leukemia (AML). METHODS: The clinical data of 55 children who were diagnosed as t (8; 21)/AML1-ETO-positive AML were retrospectively studied. Event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis software. RESULTS: Of the 55 patients, 4 patients gave up treatment after the diagnosis was confirmed and 4 patients were lost to follow-up after the first chemotherapy course. The remaining 47 patients received a double-induction therapy. The total complete remission (CR) rate was 71% and 94% after the first and second chemotherapy course, respectively. The disease was relapsed in 10 patients (21%). The 5-year EFS, DFS and OS rates were (56.1 ± 7.9)%, (59.8 ± 8.1)%, and (72.0 ± 8.1)%, respectively. Multivariate analysis showed that age was an independent risk factor for the long-term prognosis. The older children had a greater risk of experiencing an accident or death (P<0.05). The 5-year OS rate in 27 patients with regular consolidation chemotherapy was significantly higher than 13 patients with irregular chemotherapy after CRz [(47.5 ± 17.1)% vs (38.9 ± 17.3)%; P<0.01]. CONCLUSIONS: Childhood t(8;21)/AML1-ETO-positive AML is a highly heterogeneous disease, with a high CR rate and a good long-term prognosis. Age is one of the important factors affecting the long-term therapeutic effect. Regular consolidation chemotherapy applied after CR usually is helpful.