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.

Hemophagocytic Lymphohistiocytosis Secondary to Juvenile Myelomonocytic Leukemia: A Case Report and Review of the Literature.

RATIONALE: Juvenile myelomonocytic leukemia (JMML) is a rare hematopoietic disorder, which is more rarely accompanied by monosomy 5 or deletion of the long arm of chromosome 5q (-5/5q-) or monosomy 5 (5q-/-5), and hemophagocytic lymphohistiocytosis (HLH) is a rare, uncontrolled hyperinflammation condition, which is more rarely secondary to JMML. Up to now, only a few cases of JMML with -5/5q- and HLH secondary to JMML were described. Here we described an extremely rare case of HLH second to JMML with 5q-. PATIENT CONCERNS: The patient had multiple cafe-au-lait-spots at birth and was found that NF1 gene mutation was positive. At his 6 years old, he developed hepatosplenomegaly, anemia, thrombocytopenia, monocyte count 4.12×109/L in peripheral blood, 13% blasts in peripheral blood, and 11% blasts in bone marrow, without BCR/ABL rearrangement, combining with positive NF1 gene mutation, he was diagnosed as JMML. In the bone marrow, there was chromosomal abnormalities with -5/5q-. In the treatment, HLH occurred. DIAGNOSES: The patient was diagnosed as secondary HLH to JMML. INTERVENTIONS: The patient received the chemotherapy treatment of the improved diffuse alveolar hemorrhage protocol, and meanwhile, he prepared for hematopoietic stem cell transplantation. Then on the basis of anti-infection, symptomatic and supportive therapy, he was commenced the treatment according to the HLH-2004 protocol. OUTCOMES: He had a partial response, manifesting that his fever resolved, but the blood coagulation function did not improve, and the severe thrombocytopenia remained. Then, the parents refused the continual treatment, and the child died of intracranial hemorrhage 3 months after the diagnosis of JMML. LESSONS: JMML and HLH were relatively easy to diagnose based on clinical and laboratory results. Due to the low incidence of JMML with -5/5q- and HLH secondary to JMML, no clinical practice guidelines for the treatment of the disease have been established yet. The clinical data of a case of HLH secondary to JMML with 5q- were analyzed, and relevant studies were studied.

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.

Adolescents experienced more treatment failure than children with chronic myeloid leukemia receiving imatinib as frontline therapy: a retrospective multicenter study.

To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0-8 years for girls and 0-10 years for boys), adolescents (9-19 years for girls and 11-19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20-39 years, n = 305; cohort 4: age 40-59 years, n = 270; and cohort 5: age 60-83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3-161 months) in children, 33 months (range, 3-152 months) in adolescents, and 48 months (range, 3-157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response4.5. Notably, compared with not only adults (cohort 3 vs. cohort 1: HR = 2.03 [1.03, 3.98], P = 0.040; cohort 4 vs. cohort 1: HR = 2.15 [1.07, 4.33], P = 0.033; cohort 5 vs. cohort 1: HR = 4.22 [1.94, 9.15], P < 0.001) but also adolescents (cohort 2 vs. cohort 1: HR = 2.36 [1.18, 4.72], P = 0.015), children had significantly longer failure-free survival. Age was not associated with progression-free survival or overall survival. Although they exhibited more aggressive clinical features at diagnosis, both children and adolescents achieved superior treatment responses than adults. Adolescents showed even more adverse features and a poor FFS than children.

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.

[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.

[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.

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: 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.

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.

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.