Efficacy and Safety of Children With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia After Anti-CD19 CAR T-Cell Therapy Without Bridging Transplantation.

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, a considerable number of patients experience relapse within 1 year after CAR T-cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation. MATERIALS AND METHODS: In our study, we investigated 42 children with R/R B-ALL who underwent anti-CD19 CAR T-cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity. RESULTS: The cohort that received the CAR T-cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% ± 8.5%, and the event-free survival (EFS) was 55.9% ± 7.9%, with a median follow-up duration of 50.1 months. Minimal residual disease (MRD) ≥1% was associated with inferior outcomes, resulting in lower 4-year OS (P = .033) and EFS (P = .014) compared to MRD<1%. The incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD≥1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity. CONCLUSION: These findings suggest that reducing the pre-infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T-cell therapy.

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: Oure 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 CR, and within one 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 HSCT or not. Conclusion: CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

[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.

Neural-network-based wavefront solution algorithm for a wide field survey telescope.

The wide field survey telescope (WFST) is a 2.5 m optical survey telescope currently under construction in China. The telescope employs a primary-focus optical design to achieve a wide field of view of 3 deg, and its focal plane is equipped with four pairs of curvature sensors to perform wavefront sensing and active optics. Currently, there are several wavefront solution algorithms available for curvature sensors, including the iterative fast Fourier transform method, orthogonal series expansion method, Green's function method, and sensitivity matrix method. However, each of these methods has limitations in practical use. This study proposes a solution method based on a convolutional neural network model with a U-Net structure for the curvature wavefront sensing of the WFST. Numerical simulations show that the model, when properly trained, has a high accuracy and performs a curvature wavefront solution effectively. Upon a comparison with the sensitivity matrix method, this new method demonstrates its superiority. Finally, the study is summarized, and the drawbacks of the proposed method are discussed, which leads to direction for future optimizations.

Diagnostic Value and Prognosis Significance of Cerebrospinal Fluid Examination by Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia.

Purpose: To explore the diagnostic value and the prognostic significance of cerebrospinal fluid (CSF) examination by flow cytometry (FC) in children with central nervous system leukemia (CNSL). Method: This is a retrospective observational study. We select 986 pediatric patients with newly diagnosed acute lymphoblastic leukemia from January 2012 to December 2018 as the research objects and analyze the sensitivity and specificity of different methods for diagnosing CNSL. The recurrence rate and survival rate of CNSL in different groups were compared. Results: Among the 986 cases, 31 cases (positive rate of 3.14%) were positive by FC, and the cytospin-based cytomorphology (CC) test was positive in 6 cases (positive rate of 0.61%). CC combined with FC might improve the diagnostic sensitivity (from 30% to 65%, 𝑥2 value was 5.143, P = .016). The 2-year event-free survival (EFS) of 31 FC + children was 59.5% ± 9.2%, and that of 955 FC - children was 74.1% ± 1.8% (P = .004). The 2-year overall survival (OS) of the 2 groups were 63.6% ± 9.7% and 80.2% ± 1.5%, respectively (P = .004). In order to exclude the influence of CNSL, we divided the patients into 3 groups: CNSL group and non-CNSL group with CSF FC + , FC - group. There was no significant difference in EFS between FC - group and non-CNSL group with FC + (2-year EFS were 74.1% ± 1.8% and 68.7% ± 9.8%, respectively, P = .142), and there was a significant difference in OS (2-year OS were 80.2% ± 1.5% and 67.5% ± 10.3%, respectively, P = .029). Conclusion: The test of FC combined with CC may improve the diagnostic sensitivity of CNSL. The EFS and OS of children with FC + are worse than those of children with FC -. However, for those patients with non-CNSL, but only FC + at the initial diagnosis, the EFS is not significantly affected by strengthening systemic chemotherapy and increasing the number of intrathecal injections.

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.

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.

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 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.

Comparisons of Long-Term Survival and Safety of Haploidentical Hematopoietic Stem Cell Transplantation After CAR-T Cell Therapy or Chemotherapy in Pediatric Patients With First Relapse of B-Cell Acute Lymphoblastic Leukemia Based on MRD-Guided Treatment.

Measurable residual disease (MRD) positivity before haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an independent prognostic factor in determining outcomes in patients with B-cell acute lymphoblastic leukemia (ALL). In this study, we conducted a parallel comparison of the efficacy and safety in patients with suboptimal MRD response after reinduction who underwent haplo-HSCT after chimeric antigen receptor T-cell (CAR-T) therapy or chemotherapy. Forty B-cell ALL patients who relapsed after first-line chemotherapy and with an MRD ≥0.1% after reinduction were analyzed. The median pre-HSCT MRD in the CAR-T group (n = 26) was significantly lower than that in the chemotherapy group (n = 14) (0.009% vs. 0.3%, p = 0.006). The CAR-T group exhibited a trend toward improved 3-year leukemia-free survival and a significantly improved 3-year overall survival compared to the chemotherapy group [71.8% (95% confidence interval (CI): 53.9-89.6) vs. 44.4% (95% CI: 15.4-73.4), p = 0.19 and 84.6% (95% CI: 70.6-98.5) vs. 40.0% (95% CI: 12.7-67.2), p = 0.008; respectively]. Furthermore, no increased risk of graft-versus-host disease, treatment-related mortality, or infection was observed in the CAR-T group. Our study suggests that CAR-T therapy effectively eliminates pre-HSCT MRD, resulting in better survival in the context of haplo-HSCT.

Haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission.

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT. METHODS: A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed. RESULTS: Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR. CONCLUSION: Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

Quantitative analysis of IKZF1 gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia: higher levels are associated with a poorer prognosis.

To assess the prognostic effect of different levels of IKZF1 gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 Δ2-8/ALB deletions were quantified using multiplex real-time quantitative PCR in newly diagnosed pediatric BCP-ALL patients. Seventy-four patients with IKZF1 deletions ≥ 0.01% were included. Clinical characteristics, laboratory data, and treatment outcomes were analyzed. The patients were divided into two groups: IKZF1 deletions <1% (group A) and ≥1% (group B). Group B patients had a higher BCR-ABL1 positive rate than group A patients. The proportions of patients who had an age at onset ≥10 years old, and white blood cell count ≥50 × 109/L were significantly higher in group B than in group A. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates in group B were 79 ± 8.8% and 62.4 ± 9.7%, respectively, being significantly lower than those in group A (97.7 ± 2.2% and 83.2 ± 5.8%, respectively). The level of IKZF1 deletions ≥1% and the central nervous system leukemia were independent risk factors of EFS. Pediatric BCP-ALL patients with high levels of IKZF1 gene deletions have a poorer prognosis than those with low levels.

Outcomes of Adolescent Patients with Acute Lymphoblastic Leukemia: Long-term Follow-up of 335 Patients.

BACKGROUND: Adolescents (aged 10-17 years) with acute lymphoblastic leukemia (ALL) represent a unique patient population, with a disproportionate survival disadvantage compared with younger patients. We aimed to determine the outcomes and prognostic factors of adolescent patients treated at our institution. PATIENTS AND METHODS: Between 2005 and 2017, 335 adolescents with ALL were enrolled; clinical characteristics and treatment outcomes were analyzed and compared between adolescents and younger children (1-9 years old, n = 704). RESULTS: Adolescents were more likely to have high-risk factors such as hyperleukocytosis, a T-cell immunophenotype, BCR-ABL1, and/or poor early treatment responses. Compared with younger children, adolescents had significantly worse 5-year event-free survival (EFS) (73.0% ± 2.5% vs. 82.6% ± 1.5%; P < .001) and overall survival (OS) (77.1% ± 2.3% vs. 87.7% ± 1.3%; P < .001). Furthermore, younger adolescents (10-14 years) tended to have better outcomes compared with those older than 15 years (5-year OS: 79.3% ± 2.5% vs. 68.4% ± 5.7%; P = .042), mainly because of the lower frequencies of toxicities. On multivariate analysis, white blood count ≥ 50 × 109/L and extramedullary involvement at diagnosis were the most powerful prognostic factors for both OS and EFS. CONCLUSION: The outcomes among adolescent patients were not as good as that of younger children. Further studies are required to define optimal treatment strategies for adolescents, particularly those aged 15 to 17 years.

Predictive impact of residual disease detected using multiparametric flow cytometry on risk stratification of paediatric acute myeloid leukaemia with normal karyotype.

INTRODUCTION: Residual disease (RD) detected using multiparametric flow cytometry (MFC) is an independent predictive variable of relapse in acute myeloid leukaemia (AML). However, RD thresholds and optimal assessment time points remain to be validated. MATERIAL AND METHODS: We investigated the significance of RD after induction therapy in paediatric AML with normal karyotype between June 2008 and June 2018. Bone marrow samples from 73 patients were collected at the end of the first (BMA-1) and second (BMA-2) induction courses to monitor RD using MFC. RESULTS: Presence of RD after BMA-1 and/or BMA-2 correlated with poor relapse-free (RFS) and overall survival at 0.1% RD cutoff level. Receiver operating characteristic curve showed that RD cutoff levels of 1.3% and 0.5% after BMA-1 and BMA-2, respectively, predicted events with the highest sensitivity and specificity. In multivariable analysis, RD after BMA-2 was the strongest independent risk predictor for poor RFS (hazard ratio 2.934; 95% confidence interval: 1.106-7.782; P = .031). CONCLUSIONS: Our study therefore suggests that an RD level ≥0.5% after BMA-2 has a significant predictive impact on the prognosis of AML patients having normal karyotype and thus guide the stratification of treatment strategies.

Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy.

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.

Method of combining thermal homology theory with a genetic algorithm for the design and optimization of precise submillimeter-wave antennas.

It is a common problem in precise submillimeter-wave telescopes that thermal deformation coupling between major subsystems results from materials with different coefficients of thermal expansion or at different temperatures. Here, the method of combining thermal homology theory with a genetic algorithm (CTHTGA) is proposed for the design and optimization of large precise submillimeter-wave antennas. The CTHTGA method has two key steps: (1) design of the structure of the antenna according to thermal homology theory; and (2) structural optimization based on the genetic algorithm. It has the ability to solve the problem of thermal deformation coupling well and to ensure sufficient rigidity. As an application, CTHTGA was used in the design and optimization of a 1.2 m submillimeter-wave telescope. The results showed that the CTHTGA method, compared to the previous design of a 1.2 m antenna, not only dramatically decreases the impact of thermal deformation coupling but gives the designed antenna sufficient stiffness and smaller gravity deformation. Moreover, other things being equal, a method of combining thermal homology theory with zero-order and a first-order compound optimization algorithm is used to quantitatively validate the CTHTGA method. As the results suggest, the overall performance of the CTHTGA is, to the best of our knowledge, better than that of the latter method.

Applications of the elastic modes of a circular plate in wavefront correction of the adaptive optics and the active optics.

The elastic modes of a general circular thin plate (EMCTP), reflecting the natural deformation of the resonance, are applied to the diffraction theory of the optical aberrations in this paper. Our work has shown that the mode shapes of the EMCTP resemble those of the Zernike polynomials. As an application example, the compensations of some low order aberrations of the 2.5 m-wide field survey telescope (WFST) have been performed with the EMCTP. Moreover, a quantitative comparative study of the active optics corrections for the EMCTP and the Zernike polynomials is presented in the numerical analysis. The quantitative analysis results have demonstrated that the efficiency of the EMCTP is superior to the standard Zernike polynomials as well as the annular Zernike polynomials.

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy in Children With Central Nervous System Leukemia.

BACKGROUND: chimeric antigen receptor-modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment. PATIENTS AND METHODS: We enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid. RESULTS: After CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease-negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care. CONCLUSION: CAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.

[The Impact of Induction Treatment Response on the Prognosis of Pediatric Core Binding Factor-Acute Myeloid Leukemia Patients].

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed．The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION: NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.