Longitudinal changes in body mass index, height, and weight in children with acute myeloid leukemia.

BACKGROUND: This study reported height prediction and longitudinal growth changes in Chinese pediatric patients with acute myeloid leukemia (AML) during and after treatment and their associations with outcomes. METHODS: Changes in 88 children with AML in percentages according to the growth percentile curve for Chinese boys/girls aged 2-18/0-2 years for body mass index (BMI), height, and weight from the time of diagnosis to 2 years off therapy were evaluated. The outcomes of AML were compared among patients with different BMI levels. RESULTS: The proportion of underweight children (weight < 5th percentile) increased significantly from the initial diagnosis to the end of consolidation treatment. The proportion of patients with low BMI (BMI < 5th percentile) was highest (23.08%) during the consolidation phase, and no children were underweight, but 20% were overweight (BMI > 75th percentile) after 2 years of drug withdrawal. Unhealthy BMI at the initial diagnosis and during intensive chemotherapy leads to poorer outcomes. For height, all patients were in the range of genetic height predicted based on their parents' height at final follow-up. CONCLUSIONS: Physicians should pay more attention to the changes in height and weight of children with AML at these crucial treatment stages and intervene in time.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

Case report of pediatric TTMV-related acute promyelocytic leukemia with central nervous system infiltration and rapid accumulation of RARA-LBD mutations.

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

Clinical characteristics of SARS-CoV-2 Omicron variant infection in children with acute leukemia.

Hematologic diseases and various therapeutic stages can impact the presentation of SARS-CoV-2 Omicron variant infection. This study retrospectively analyzed data on Omicron infection in children with acute leukemia treated at our hospital between January 16, 2023, and February 25, 2023, using questionnaires. The prevalence of Omicron infection in children undergoing consolidation chemotherapy, maintenance chemotherapy, drug withdrawal, and healthy children was 81.8%, 75.2%, 55.2%, and 61.9%, respectively. The observed differences were statistically significant (P < 0.05). During the course of infection, children with leukemia undergoing chemotherapy, including both the consolidation and maintenance chemotherapy groups, exhibited a prolonged time to achieve SARS-CoV-2 negativity compared to the drug withdrawal and healthy groups. However, there was no significant increase in the incidence of symptoms across all body systems, and no children experienced serious sequelae or death. Furthermore, our observations indicated that all manifestations of Omicron infection in children with leukemia after drug withdrawal were not significantly different from those in healthy children. This suggested, to a certain extent, that the immune function of children with leukemia recovers effectively after the cessation of drug treatment. These findings are crucial for guiding clinical management and alleviating concerns about infection for both children with leukemia and their parents.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Homoharringtonine-Based Induction Therapy Reduces the Recurrence Rate of Pediatric Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for acute myeloid leukemia (AML). Pediatric patients with AML who relapse after HSCT have an extremely poor prognosis. We performed a retrospective study of pediatric patients diagnosed with AML from August 2015 to October 2019 who were treated with HSCT. Kaplan-Meier analyses were used to evaluate overall survival (OS), event-free survival (EFS), and cumulative recurrence rate (CRR). Cox regression analysis was used to determine the association between the baseline characteristics and relapse. A total of 37 pediatric patients met the inclusion criteria. Twenty-eight (75.7%) patients survived, and 9 (24.3%) patients died. The OS rates of AML patients treated with HSCT were 89.2% ± 5.1%, 75.7% ± 7.1%, and 75.7% ± 7.1% at 1, 3, and 5 years, respectively, and the CRRs were 11.4% ± 5.4%, 24.7% ± 7.7%, and 33.1% ± 10.4% at 1, 3, and 5 years after HSCT, respectively; four of nine children who relapsed after transplantation died. Induction with etoposide rather than homoharringtonine and fungal infections could be high-risk factors for recurrence after transplantation. The association between homoharringtonine-based induction therapy and a low recurrence rate persisted after adjusting for age, sex, risk stratification, fusion genes, and fungal infections. This study clarifies the clinical features and poor prognosis of post-transplant relapse in pediatric AML and indicates the urgent need for effective therapy for patients who relapse after HSCT.

Tracing back of relapse clones by Ig/TCR gene rearrangements reveals complex patterns of recurrence in pediatric acute lymphoblastic leukemia.

INTRODUCTION: Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of Ig/TCR gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse. METHODS: Clonal Ig/TCR gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ-PCR approach targeting the patient-specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back-traced to diagnostic and follow-up BM samples from 12 patients. RESULTS: Comparison of Ig/TCR gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B-ALL and 5 (33.3%) T-ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B-ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ-PCR, with a median level of 5.26 × 10-2 . The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back-tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre-existing subclones but also through an ongoing clonal evolution during remission and relapse. CONCLUSION: Backtracking Ig/TCR gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse.

Effects of waterlogging at different growth stages on the photosynthetic characteristics and grain yield of sorghum (Sorghum bicolor L.).

Various plants, including sorghum (Sorghum bicolor L.), are exposed to waterlogging; however, little is known about the effects of waterlogging at different growth stages on sorghum. A pot experiment was conducted using two sorghum hybrids, Jinuoliang 01 (JN01) and Jinza 31 (JZ31), to investigate the effects of waterlogging at different growth stages on the photosynthesis enzyme activity, chlorophyll content, malondialdehyde (MDA) content, photosynthetic parameters, dry matter accumulation, and grain yield. The experiment was conducted using waterlogging treatments implemented at the five-leaf stage (T1), flowering stage (T2), and filling stage (T3), using standard management (no waterlogging) as a control (CK). The adverse effects of waterlogging on sorghum growth varied with the waterlogging timing, with the maximum impact at T1, followed by T2 and T3. JZ31 was more sensitive to waterlogging compared to JN01. Waterlogged conditions inhibited the photosynthetic enzyme activity and reduced the chlorophyll content and photosynthesis, ultimately lowering the biomass yield and grain yield. The maximum yield loss was observed with the T1 waterlogging treatment; the grain yield of JN01 and JZ31 decreased by 52.01-54.58% and 69.52-71.97%, respectively, compared with CK. Furthermore, the decline in grain yield in T1 was associated with reducing grain number per panicle. These findings indicate that sorghum is sensitive to waterlogging at the five-leaf stage and JZ31 is more sensitive to waterlogging than JN01, which may provide a basis for selecting genotypes and management measures to cope with waterlogging in sorghum.

Current Anesthesia Practices of Pediatric Cardiac Surgeries in Tertiary Maternity and Children's Hospitals in China: A National Survey.

OBJECTIVES: To describe the current development of Chinese pediatric cardiac anesthesia practices. DESIGN: Descriptive research study. SETTING: This study used electronic questionnaires. The authors searched the official website of the National Health Commission of the People's Republic of China for tertiary maternity and children's hospitals across the country. PARTICIPANTS: Tertiary maternity and children's hospitals. INTERVENTIONS: All representatives of the invited hospitals were asked to report the official statistics of their hospitals whenever possible. MEASUREMENTS AND MAIN RESULTS: The survey questions were related to the geographic distribution and caseloads of pediatric cardiac surgical resources, technical capacities, anesthetic regimens, monitoring practices, and qualification requirements of anesthesiologists. A total of 130 hospitals were confirmed, using the registration information of the National Health Commission of the People's Republic of China, and 108 hospitals agreed to participate in this study. All enrolled hospitals completed the questionnaires, of which 52 could perform cardiac surgeries and were located in provinces, autonomous regions, and municipalities across the country, except for the Inner Mongolia Autonomous Region, Ningxia Hui Autonomous Region, and Tibet Autonomous Region. The authors found that most hospitals' caseload of pediatric cardiac surgeries was relatively small (<500 cases per year). Hospitals capable of performing high-risk pediatric cardiac surgeries are mainly located in Eastern China. Most hospitals prefer total intravenous anesthesia in cardiac surgeries, and commonly used anesthetics include propofol, sufentanil, rocuronium, and cisatracurium. Except for the basic intraoperative monitoring items (including electrocardiography, invasive blood pressure, central venous pressure, pulse oxygen saturation, intake-output volume, and body temperature), bispectral index and near-infrared spectroscopy are relatively commonly used in some hospitals. Postoperative analgesia for children undergoing cardiac surgeries was provided in 38 hospitals, and an intravenous analgesia pump was the most widely used analgesia measure. In addition, the most frequently mentioned qualification requirements for pediatric cardiac anesthesiologists in these hospitals specializing in cardiac surgeries were a further study in domestic hospitals specializing in cardiac surgeries and the professional titles of the attending doctors. CONCLUSIONS: Pediatric cardiac medical resources are mainly concentrated in Eastern China, and most hospitals capable of performing high-risk cardiac surgeries are located in the eastern part of the country. The authors found that pediatric cardiac anesthesia practices varied widely among the hospitals, and the main problem with pediatric cardiac anesthesia in China is that there is no systemic fellowship training curriculum at present; therefore, there is an urgent need to develop a fellowship training curriculum to further improve the quality of Chinese pediatric cardiac anesthesia.

DNMT3A low-expression is correlated to poor prognosis in childhood B-ALL and confers resistance to daunorubicin on leukemic cells.

BACKGROUND: Little is known about DNMT3A expression and its prognostic significance in childhood B cell acute lymphoblastic leukemia (B-ALL). METHODS: We determined DNMT3A mRNA expression in 102 children with B-ALL. Correlations with relapse-free survival (RFS) and common clinical characteristics were analyzed. DNMT3A was stably knocked out by CRISPR/Cas9 gene editing technology in Reh and 697 B-ALL cell lines. Cell proliferation activity after treated with daunorubicin (DNR) was determined by CCK8 assay in DNMT3A KO Reh and 697 cell lines. RESULTS: DNMT3A expression in B-ALL patients who were in continuous complete remission (CCR) was higher than in those who got relapse (P = 0.0111). Receiver operating characteristic curve showed prognostic significance of DNMT3A expression (P = 0.003). Low expression of DNMT3A (≤ 0.197) was significantly correlated with poor RFS (P < 0.001) in children with B-ALL. Knock-out of DNMT3A in Reh and 697 cell lines significantly increased IC50 of DNR (P = 0.0201 and 0.0022 respectively), indicating elevated resistance to DNR. CONCLUSION: Low expression of DNMT3A associates with poor prognosis in children with B-ALL. Knock-out of DNMT3A confers resistance to DNR on leukemic cells.

USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis.

The effect of aerobic glycolysis remains elusive in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Increasing evidence has revealed that dysregulation of deubiquitination is involved in glycolysis, by targeting glycolytic rate-limiting enzymes. Here, we demonstrated that upregulated deubiquitinase ubiquitin-specific peptidase 1 (USP1) expression correlated with poor prognosis in pediatric primary T-ALL samples. USP1 depletion abolished cellular proliferation and attenuated glycolytic metabolism. In vivo experiments showed that USP1 suppression decreased leukemia progression in nude mice. Inhibition of USP1 caused a decrease in both mRNA and protein levels in lactate dehydrogenase A (LDHA), a critical glycolytic enzyme. Moreover, USP1 interacted with and deubiquitinated polo-like kinase 1 (PLK1), a critical regulator of glycolysis. Overexpression of USP1 with upregulated PLK1 was observed in most samples of patients with T-ALL. In addition, PLK1 inhibition reduced LDHA expression and abrogated the USP1-mediated increase of cell proliferation and lactate level. Ectopic expression of LDHA can rescue the suppressive effect of USP1 silencing on cell growth and lactate production. Pharmacological inhibition of USP1 by ML323 exhibited cell cytotoxicity in human T-ALL cells. Taken together, our results demonstrated that USP1 may be a promising therapeutic target in pediatric T-ALL.

Study on predictive factors of blood culture results in leukemia patients with fever during chemotherapy.

Infection is a common complication of leukemia patients undergoing chemotherapy. Blood culture results are often needed to guide clinical use, but repeated sampling is often necessary to improve the positive rate and eliminate contamination. The purpose of this paper is to find predictive factors of blood culture results among clinical and laboratory indicators and try to establish a prediction model, so as to better choose the time of blood culture examination, predict the results, and better guide clinical treatment. We retrospectively collected clinical and laboratory data of febrile acute leukemia patients undergoing chemotherapy. The samples were randomly assigned to the training set and the validation set, and the prediction model was constructed from the training set. The calibration curve was made in the validation set and the Hosmer-Lemeshow test was performed to evaluate the prediction performance of the prediction model. A total of 229 patients were included. Univariate and multivariate analyses suggested that temperature at fever and procalcitonin were variables of significant difference between positive and negative blood culture patients. The sensitivity of the 2 variables for predicting blood culture results was high, but the specificity was low. In the process of external validation, the predictive ability of the constructed prediction model to the blood culture results was low. This study identified clinical and laboratory parameters associated with blood culture outcomes, but the predictive model established has low predictive accuracy in external validation.

Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia during remission induction chemotherapy: a single-center retrospective study.

BACKGROUND: This study investigated the clinical characteristics, cranial magnetic resonance imaging (MRI) features, MRI follow-up, and prognosis of children with acute lymphoblastic leukemia (ALL) who developed posterior reversible encephalopathy syndrome (PRES) during remission induction chemotherapy. METHODS: We analyzed the age, gender, PRES symptoms and signs, cranial MRI findings, therapeutic effect, and prognosis of children with ALL who developed PRES during chemotherapy from January 2010 to December 2013 at the Hematology Oncology Center of Beijing Children's Hospital. Changes in cranial MRI findings were analyzed, and intelligence (IQ) and cognitive function were evaluated using the Wechsler Scale and the Wisconsin Card Score Test after the children completed chemotherapy. RESULTS: There were 850 children with newly diagnosed ALL in this period; 13 (1.5%), 6 boys and 7 girls, developed PRES. All were diagnosed as B-cell ALL. The median age at PRES onset was 7 years (2-11 years). The median day of PRES onset was day 28 (day 17-34) of remission induction chemotherapy. Of the 13 children with PRES onset and seizures, 4 had visual disturbances and 2 had consciousness disturbances. Cranial MRI showed hyperintensity in the subcortical white matter on T2-weighted axial and fluid-attenuated inversion recovery (FLAIR) images. The lesion locations were as follows: occipital lobe, 12 (92.3%) patients; frontal lobe, 7 (53.8%) patients; temporal lobe, 5 (38.4%) patients; parietal lobe, 3 (23.1%) patients; and cerebellum, 1 (7.7%) patient. There were 8 (61.5%) patients with vasogenic edema and 5 (38.5%) with cytotoxic edema. After treatment, all children recovered within one month, when their PRES symptoms were relieved, they continued to receive chemotherapy. However, 1 child (1.07%) died of severe central nervous system infection one year after PRES treatment, and 3 (25%) had recurrent seizures and were diagnosed with epilepsy after three months of PRES treatment. Their cranial MRIs showed cytotoxic edema, which was acute stage on day 15, with aggravated lesions on cranial MRI. The cranial MRI lesions returned to normal at one month in 3 (23.1%) patients, at three months in 6 (46.1%) patients, at one year in 8 (61.5%) patients, and at two years in 12 (92.3%) patients. The 12 surviving children all returned to school, and their full-scale, verbal, and performance IQs were normal, with no significant differences in intelligence or cognitive function compared with children with ALL without PRES during the same period. CONCLUSIONS: PRES can occur during remission induction chemotherapy treatment of children with ALL, but the incidence is low. Cranial MRI can be used for diagnosis and to characterize lesions. The children recover about a month after treatment, and cranial MRI lesions return to normal within two years. The time for complete resolution of MRI lesions differs, and children with cytotoxic edema have worse prognosis with sequelae, such as epilepsy, which requires close monitoring. PRES does not affect intelligence or cognitive development.

Cost-effectiveness analysis of dasatinib versus imatinib in pediatric philadelphia chromosome-positive acute lymphoblastic leukemia patients in China.

BACKGROUND: Dasatinib and imatinib are the recommended tyrosine kinase inhibitors (TKIs) for treating pediatric Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), and the one which has been approved indication in China is imatinib. Recently, clinical demand for Ph + ALL treatment is becoming unmet gradually with the increasing resistance of imatinib. There are some studies reporting the better efficacy and comparative safety of dasatinib compared with imatinib, but no economic comparison has been published. This study aims to supplement economic evidence by comparing the cost-effectiveness between imatinib and dasatinib in treating pediatric patients with Ph+ ALL in China, and to help clinical rational drug use via multi-dimensional value assessment. METHODS: A decision tree model combined with a 10-year Markov model were established based on the disease progression. The parameters were collected from published literatures and our hospital's electronic medical records. From the health system perspective, the incremental cost-effectiveness ratio (ICER) between the two treatment groups was calculated through cost-effectiveness analysis and then compared with the willingness-to-pay (WTP) threshold. The set WTP threshold in this study was 1 times per capita gross domestic product (GDP) of China, as recommended by the World Health Organization. Direct medical costs and quality-adjusted life years (QALYs) were calculated and discounted at 5%. The sensitivity analyses were conducted to assess the uncertainty and robustness of the results. RESULTS: The total costs were CNY 1,020,995.35 and CNY 1,035,788.50 in imatinib group and dasatinib group during the 10-year simulation, and the total QALYs were 2.59 and 4.84. Compared with the imatinib treatment group, the ICER was around CNY 6,575.78/ QALY, which was less than the set threshold CNY 70,892/ QALY. The sensitive analyses indicated the robustness of the results. CONCLUSIONS: The cost-effectiveness analysis shows the potential cost-effective advantages of adding dasatinib comparing with adding imatinib for pediatric Ph + ALL patients in China under the set WTP threshold, which indicates that those patients could achieve more QALYs by paying acceptable fee.

Corrigendum: Blinatumomab for treating pediatric B-lineage acute lymphoblastic leukemia: A retrospective real-world study.

[This corrects the article DOI: 10.3389/fped.2022.1034373.].

Blinatumomab for treating pediatric B-lineage acute lymphoblastic leukemia: A retrospective real-world study.

Objectives: Blinatumomab was shown to be safe and effective for consolidation therapy in B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the effectiveness and safety of blinatumomab in pediatric B-ALL patients in a real-world setting. Methods: This was a retrospective, observational study that included patients who initiated blinatumomab treatment between October 1, 2020 and June 20, 2022. Patients with B-ALL diagnosis, age below 18 years, and at least one blinatumomab treatment cycle were included. Treatment-related toxicities were assessed. Result: Totally 23 pediatric patients were included in this study, with a median age of 6 years (range, 2 to 11 years). Blinatumomab therapy was applied for MRD-positive (disease ≥0.01%, n = 3) or chemotherapy-ineligible (n = 20) B-ALL cases. The median follow-up time was 9 months, and all evaluable patients achieved complete molecular remission with undetectable MRD. Four relapsed B-ALL cases proceeded to hematopoietic stem cell transplantation (HSCT) without further bridging therapy, while the others underwent maintenance chemotherapy after blinatumomab treatment. Grade ≥3 febrile neutropenia, white blood cell decrease and seizure were observed in 57%, 48% and 4.3% of patients, respectively. One case discontinued therapy due to neurologic toxicities. Elevated cytokine levels were observed in 4 patients. In all 23 patients, increased T-cell and low B-cell counts (<10/µl) were detected during blinatumomab therapy. Conclusion: These encouraging results suggest blinatumomab in pediatric B-ALL patients with MRD+ or chemotherapy-related toxicities is effective and safe in the short run, although long-term follow-up is still needed.