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.

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.

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.

[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.

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.

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.

Characteristics and prognosis of pediatric myeloid sarcoma in the cytogenetic context of t(8;21).

The prognosis of myeloid sarcoma (MS) is controversial. Many reports indicated that orbital-MS has a good prognosis and is closely related to t(8;21), but the prognostic role of MS in pediatric t(8;21) AML is unclear. We retrospectively analyzed data from 127 patients with pediatric t(8;21) AML diagnosed between January 2010 and June 2018. We compared patients with (n = 30) and without MS (n = 97). The median follow-up time was 52.6 months. The proportion of t(8;21) AML patients with MS was 23.6%. Males were more likely to have MS than females. The complete remission rate after the first course of induction chemotherapy and the 3-year relapse-free survival (RFS) among patients with MS were lower than those among patients without MS (60% vs. 78.4%, p = 0.045) (68.8 ± 8.8% vs. 88.0 ± 3.4%, p = 0.004). The female sex and a higher level of RUNX1/RUNX1T1 transcripts after consolidation were risk factors for poor RFS among patients with MS. Our data showed that MS was an independent risk factor in pediatric t(8;21) AML. Close monitoring of measurable residual disease of the bone marrow and extramedullary lesions is needed to guide stratified treatment.

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.

Wide-field optical design for a 60 m submillimeter telescope.

We present a practical wide-field optical design for a 60 m aperture submillimeter telescope, which is currently under conceptual design study in China. The telescope is specified to operate over a wavelength range of 0.65-3 mm and provide a wide field of view (FOV) of 1° in diameter. We designed an F/6 Ritchey Chrétien (RC) system with a quasi-planar tertiary corrector, which cancels all spherical, coma, and astigmatism aberrations. It also achieves a good balance among the mirror sizes, central obscuration, and focal-plane curvature. The problems of focal surface curvature and nontelecentricity are treated in the subfield instrumental design, which employs a simple silicon wedge prism to obtain flat and telecentric focal planes for each subfield instrument module. Our studies show that by such a design, more than ${{10}^5}$105 detector pixels can be efficiently and uniformly fed at the shortest wavelength band with Strehl ratios above 0.85 across the entire 1° FOV. Several practical issues related to the telescope optics are also discussed.

[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.

Research on elastic modes of circular deformable mirror for adaptive optics and active optics corrections.

In this paper, an elastic mode method of deformable mirror is proposed to decompose arbitrary wave-front errors of adaptive optics system. The elastic modes are derived with an analytical method of linear piezoelectricity based on a bimorph piezoelectric deformable mirror (BPDM), and the three-dimensional formulas of elastic modes are presented. Here a BPDM with an aperture of 165 mm as an example is numerically studied. Two different kinds of dynamic boundary conditions are considered, and the dependence of the elastic modes aberrations upon the orders and rotational symmetries is evaluated. Besides, a comparative study for elastic mode and Zernike polynomials is presented in the numerical analysis. The results have demonstrated that the elastic mode method can be not only used instead of Zernike polynomials, but also more effective to decompose arbitrary wave-front errors of a deformable mirror. Furthermore, finite element analysis method is used to validate the analytic method. The conclusions have shown reasonably consistent results between the two methods.

Multi-variable H-ß optimization approach for the lateral support design of a wide field survey telescope.

We have proposed a multi-variable H-ß optimization approach (MHOA). Compared with the conventional push-pull-shear lateral support optimization (CPLSO), which has only one design variable, ß, MHOA adds another design variable, H, which is the support position height. By contrast, the support position height of CPLSO is usually fixed at mid-thickness, Hm (or at H0, the height of the center of gravity for the mirror), on the outer rim of the mirror blank. In addition, hybrid optimization with the sub-problem approximation method and first order method is also applied in MHOA. To verify the feasibility and the advancement, the optimization of the lateral support of the 2.5 m-wide field survey telescope (WFST) is performed with MHOA in this paper. Three designs with different supporting points, including 18 supporting points, 24 supporting points, and 36 supporting points, are obtained, and the residual half path length errors are 23.71 nm, 19.60 nm, and 17.79 nm, respectively. Furthermore, other things being equal, CPLSO with H=H0 as well as CPLSO with H=Hm are used separately to validate the H-ß design idea quantitatively. The results have suggested that limiting the value of the residual half path length error, obtained by MHOA, has improved almost 20 nm compared to that of CPLSO with H=H0, and almost 10 nm compared with that of CPLSO with H=Hm.

[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.

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.

[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.