OBJECTIVE:To evaluate the efficacy and safety of blinatumomab in the treatment of children with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), and to explore the factors affecting the efficacy of blinatumomab. METHODS:The clinical data of 21 children with R/R B-ALL who received treatment with blinatumomab in the Department of Pediatrics, Peking University People's Hospital from April 2021 to December 2023 were retrospectively analyzed. RESULTS:Among the 21 children, there were 10 boys and 11 girls, with a median age of 4(2-17) years. There were 5 cases of isolated bone marrow relapse, 1 case of bone marrow combined with central nervous system relapse, 3 cases of isolated minimal residual disease (MRD) relapse, 5 cases of isolated molecular relapse, 2 cases of MRD combined with molecular relapse, and 5 cases of refractory disease. In 8 children with baseline blasts ≥5% before blinatumomab treatment, 7 cases (87.5%) achieved complete remission (CR) after treatment, and 3 cases (37.5%) achieved MRD negativity. There were 13 children with positive MRD and/or molecular markers (with bone marrow CR) before blinatumomab treatment, of whom 12 cases (92.3%) achieved MRD and/or molecular negativity after treatment. The median follow-up time of the 21 children was 13.1(6.5-34.9) months, with a 1-year overall survival (OS) rate of (92.3±7.4)%. The factors affecting the short-term efficacy of blinatumomab included the baseline blasts (P =0.026) and MRD level (P =0.026) before treatment. No grade 3 or higher cytokine release syndrome (CRS) occurred, and no neurological events were observed. CONCLUSION:The short-term efficacy of blinatumomab in pediatric R/R B-ALL is excellent, particularly in children with low tumor burden. The clinical adverse events are controllable, and the safety profile is favorable.

We measured dasatinib concentrations in paired plasma and cerebrospinal fluid (CSF) samples from children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Blood samples were collected from children at 0 h (pre-dasatinib) and 2 h post-dasatinib, along with CSF. After validating a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for dasatinib in both matrices, we quantified drug concentrations in plasma and CSF and expressed blood-brain barrier penetration as the plasma-to-CSF concentration ratio. Twenty children with Ph+ ALL, who received oral dasatinib (60-80 mg/m2·day), were included in this study. The median age was 10.8 (5-16) years, with 13 males (65%) and 7 females (35%). In plasma, the mean dasatinib concentrations were 1.3 ± 0.7 ng/mL at 0 h and 101.6 ± 42.1 ng/mL at 2 h. In CSF, the mean dasatinib concentration was 0.5 ± 0.2 ng/mL at 2 h. The median paired plasma/CSF concentration ratio was 225:1 (98:1-406:1). In conclusion, despite therapeutic systemic levels, dasatinib penetrates poorly into CSF in children with Ph+ALL.

Objective To explore the clinical characteristics and prognostic factors of pediatric acute myeloid leukemia(AML)with monosomy 7(-7)and deletion of the long arm of chromosome 7(7q-).Methods A retrospective study was conducted on the clinical data,treatment,and prognosis of children with-7/7q-AML who were admitted to the Department of Pediatrics at Peking University People's Hospital from January 2010 to December 2024.Results A total of 869 children with AML who had complete karyotype data were included,of whom 32(3.7%)had-7/7q-chromosomal abnormalities.There were 20 males and 12 females,and the median age at diagnosis was 6 years.Six children(19%)had isolated-7;2(6%)had isolated 7q-;and 24(75%)had additional chromosomal abnormalities.After induction chemotherapy,complete remission(CR)was achieved in 16 children(50%).At the last follow-up,15 children(47%)had died and 17(53%)were alive.The 3-year disease-free survival(DFS)rate was(54.1±0.1)%,and the 3-year overall survival(OS)rate was(52.6±0.1)%.The multivariable analysis showed that hematopoietic stem cell transplantation(HSCT)was an independent prognostic factor for DFS(HR=0.17,95%CI:0.04-0.62,P=0.008)and OS(HR=0.16,95%CI:0.04-0.59,P=0.006),with better outcomes in children who underwent HSCT.Conclusions The incidence of-7/7q-chromosomal abnormalities in children with AML is 3.7%.Additional chromosomal aberrations are common,and the CR rate after induction chemotherapy is low.HSCT is associated with improved prognosis and survival.

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy is a potent treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, patients harboring TP53 alterations experience disproportionately high relapse rates, and the underlying tumor-intrinsic mechanisms driving this resistance remain poorly understood.MethodsWe engineered isogenic TP53-wildtype and TP53-knockout NALM-6 B-ALL cell models using CRISPR/Cas9. The specific impact of p53 loss on CD19 CAR-T cell cytotoxicity, proliferation, and exhaustion was evaluated using in vitro co-culture assays. Associated molecular alterations and adaptive responses were profiled via RNA-sequencing (RNA-seq).ResultsIn in vitro assays, TP53-deficient B-ALL cells exhibited intrinsic resistance to CAR-T-mediated killing. Co-culturing with these TP53-null targets reduced CAR-T cell expansion, suppressed effector cytokine secretion, and accelerated a T-cell exhaustion phenotype, indicated by the co-expression of PD-1, TIM-3, and LAG-3. Transcriptomic profiling revealed that TP53 deficiency induces a low-adhesion signature, characterized by the coordinated downregulation of core extracellular matrix (ECM) and cell adhesion genes, including ITGB1 and LAMA5. This transcriptional profile suggests a structural remodeling that potentially deprives CAR-T cells of the mechanical anchoring requisite for establishing a stable immunological synapse (IS). Furthermore, TP53-deficient cells failed to activate immunogenic signaling pathways, such as IL-2/STAT5, under immune pressure.ConclusionsOur in vitro findings indicate that TP53 deficiency in B-ALL cells downregulates adhesion networks and impairs immunogenic signaling, which correlates with accelerated CAR-T cell exhaustion. These transcriptomic and cellular observations suggest a potential link between TP53-mediated adhesion loss and CAR-T resistance, warranting further in vivo validation and biophysical investigations.

NUP98 rearrangements define a high-risk, genetically heterogeneous subtype of paediatric acute myeloid leukaemia (AML), yet comprehensive clinicogenetic and survival data remain limited. This retrospective, single-centre study of 32 paediatric patients (2017-2025) found a median age of 8.7 years and predominance of the NUP98::NSD1 fusion (68.8%), frequently co-mutated with FLT3-ITD (50%) and WT1 (43.8%). Complete remission (CR) rates increased from 53.1% to 87.5% after first and second induction. With a median follow-up of 41.7 months, the estimated 3-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 81.2% (95% confidence interval [CI], 65.9%-96.5%), 62.8% (95% CI, 43.8%-81.8%) and 28.1% (95% CI, 12.9%-45.6%), respectively; corresponding rates among the 29 transplanted patients were 79.8% (95% CI, 63.5%-96.1%), 68.7% (95% CI, 50.3%-87.1%) and 26.0% (95% CI, 11.1%-43.9%) respectively. Exploratory multivariate analysis identified failure to achieve CR after induction 2 as a risk factor for OS, WT1 mutation for relapse in the entire cohort and pretransplant minimal residual disease (MRD) positivity for relapse in the transplant subgroup. This confirms that NUP98-rearranged AML necessitates intensive therapy including transplant and highlights WT1 and pretransplant MRD as key prognostic markers for risk-adapted strategies.

BACKGROUND:Pediatric chronic myeloid leukemia in the blast phase (CML-BP) is rare and high-risk, requiring early hematopoietic stem cell transplantation (HSCT). Tyrosine kinase inhibitor (TKI) combined with intensive chemotherapy prior to HSCT is associated with substantial toxicity, often causing complications that delay HSCT. Therefore, safer attenuated regimens are urgently needed. METHODS:We retrospectively analyzed CML-BP pediatric patients treated with TKI plus venetoclax and assessed treatment safety via hematological and non-hematological adverse events. RESULTS:Six pediatric patients (five males and one female) treated with TKI and venetoclax were retrospectively collected from September 2022 to September 2025, with a median age of 13 years. Four patients presented with the lymphoid blast phase (CML-LBP), one with the myeloid blast phase (CML-MBP) and one with central nervous system leukemia (CNSL). After one cycle of TKI combined with venetoclax, four patients showed a decrease in BCR::ABL1 international scales (BCR::ABL1IS) transcript ratio in bone marrow fluid was >1 log, and five patients achieved minimal residual disease (MRD)-negative. With a median follow-up of 17 months, five of the six patients were alive. The safety profile was excellent, with Grade-2-3 hematological toxicities and Grade 1 nausea in six patients, Grade 2 fever in one patient, and Grade 1 hyperbilirubinemia in one patient. All the adverse reactions were alleviated with symptomatic therapy. CONCLUSIONS:The combination of TKI and venetoclax may be a viable strategy for treating pediatric patients with CML-BP.

BackgroundDespite advances in therapy, 30%–40% of pediatric acute myeloid leukemia (AML) patients still experience treatment failure due to relapse or toxicity. Current risk stratification based on genetic features remains insufficient, and epigenetic biomarkers for pediatric AML are understudied. This study aimed to evaluate the prognostic and predictive value of PTGER4, SHOX2, and HOXA9 promoter methylation in pediatric AML.MethodsWe enrolled 69 newly diagnosed pediatric AML patients treated with standardized chemotherapy. Promoter methylation levels were measured by multiplex methylation-specific PCR. Associations between methylation status and clinical characteristics, survival outcomes, and response to hypomethylating agents (HMAs) were analyzed using univariate and multivariate Cox regression, sensitivity analyses, and subgroup validation.ResultsMethylation levels of all three genes were significantly associated with age and core binding factor abnormalities. PTGER4 methylation positivity was identified as an independent adverse prognostic factor for event-free survival (hazard ratio (HR) = 3.456, 95% CI 1.126–10.610, P = 0.030), with a significant dose-response relationship between methylation levels and survival. Subgroup analyses confirmed its prognostic value in patients with platelet count <50 × 109/L, those achieving complete remission (CR) after induction and patients within transplant group. Among PTGER4 methylation-positive patients, HMA-based therapy was associated with significantly improved 3-year overall survival (84.6% vs. 19.0%, P = 0.011).ConclusionPTGER4 promoter methylation is a promising prognostic biomarker for pediatric AML and correlates with improved response to HMAs. It could help refine risk stratification and guide individualized treatment decisions, particularly in patients with baseline thrombocytopenia and those achieving post-induction CR or receiving transplant.

OBJECTIVES:To evaluate the safety of blinatumomab combined with dasatinib in children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). METHODS:A retrospective review was conducted of clinical data for children with Ph+ ALL treated with blinatumomab plus dasatinib in the Department of Pediatrics, Peking University People's Hospital, from August 2023 to June 2025. Adverse events during therapy were recorded to assess safety. RESULTS:Ten children were included (7 boys, 3 girls), with a total of 13 instances of combination therapy. After treatment, BCR∶∶ABL1 transcript levels decreased from baseline or remained persistently negative. At a median follow-up of 13 months, all patients were alive without disease relapse. During treatment, dasatinib trough and peak plasma concentrations were not significantly affected (P>0.05). Major adverse events were as follows: hematologic toxicity (grade I-II: 77%; grade III-IV: 23%; median time to onset: 4 days; median duration: 7 days), cytokine release syndrome (all grade I; incidence: 61%; median time to onset: 3 days; duration: 2 days), neurotoxicity (grade I-II: 30%; grade III-IV: 7%; median time to onset: 3 days; duration: 1 day), and hypogammaglobulinemia (incidence: 90%; median time to onset: 13 days), with six patients requiring long-term intravenous immunoglobulin therapy. All adverse events resolved with supportive care, and no treatment-related deaths occurred. CONCLUSIONS:Blinatumomab combined with dasatinib is well tolerated in pediatric Ph+ ALL, and the adverse events are manageable.

BACKGROUND:B-cell lymphoblastic lymphoma (B-LBL) represents a rare variety of non-Hodgkin lymphoma, with limited research on its biology, progression, and management. METHODS:A retrospective analysis was performed on the clinical characteristics of 256 patients aged ≤18 years who received treatment under the China Net Childhood Lymphoma (CNCL)-NHL-2017-lymphoblastic lymphoma regimen from April 2017 to March 2023. RESULTS:Among the 256 patients, the median age at diagnosis was 5.0 years, with a slight male predominance. Subcutaneous tissues, skin, and osteolytic bone were the most common sites of the disease. More than 90% of patients exhibited disseminated disease (Stage III or IV). Approximately 19.9% of the diagnosed patients exhibited central nervous system involvement. Adverse events were observed in 33 patients (12.9%), with disease progression or relapse occurring in 10.2% of cases, particularly linked to unfavorable outcomes in instances of early relapse or progression. Salvage chemotherapy combined with immunotherapies, followed by bridging hematopoietic stem cell transplantation, significantly improved the prognosis of relapse and disease progression in children. Overall, the follow-up time was 37.6 (Q1-Q3, 28.9-38.0) months, and 3-year event-free survival rate and overall survivals were 86.3% ± 2.5% and 95.2% ± 1.5%, respectively, with a treatment-related mortality of 1.6%. Multivariate analysis showed that poor prednisone response and no complete remission on Day 33 of induction were risk factors for poor prognosis. CONCLUSION:The CNCL-NHL-2017-lymphoblastic lymphoma regimen was effective in children with B-LBL. The response to initial treatment is vital for improving prognosis in patients with B-LBL.

The incidence of paediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN) is extremely low, and little is known about the disease. This study aims to investigate its clinical course and optimal management. We retrospectively analysed the clinical manifestations, laboratory findings, treatment responses, and survival outcomes of 18 paediatric patients with BPDCN treated at our hospital. In this cohort, the male-to-female ratio was 2.6, and the median age of onset was 12 years. Bone marrow involvement was observed in 88.9

Myeloid sarcoma with erythroid differentiation represents a mass-forming presentation of acute erythroid leukemia. This entity is exceptionally rare in the pediatric population, with only sporadic reports of de novo cases predominantly involving the central nervous system or orbit. Diagnosing myeloid sarcoma with erythroid differentiation poses significant clinical and pathological challenges, particularly in cases without bone marrow involvement. Here, we report the case of a 1-year-old boy with myeloid sarcoma with erythroid differentiation exhibiting diffuse parenchymal brain infiltration without mass formation. Due to the patient’s critical condition, a tissue biopsy was unfeasible. However, cerebrospinal fluid (CSF) flow cytometry revealed a significant population of immature erythroid cells, and RNA sequencing identified an NFIA::CBFA2T3 fusion—a genetic alteration previously reported in multiple myeloid sarcoma with erythroid differentiation cases. Notably, molecular testing confirmed that the patient was negative for both TP53 mutation and chromosome 17 loss. Given the diagnostic complexity of this tumor, both flow cytometry and RNA sequencing played pivotal roles in establishing the definitive diagnosis.

Purpose To characterize relapse patterns, evaluate the prognostic value of flow cytometry minimal residual disease (FCM-MRD), and determine the optimal consolidation strategy (chemotherapy vs. allogeneic hematopoietic stem cell transplantation [allo-HSCT]) for children with first-relapsed ETV6-RUNX1 (E/R)-positive B-cell acute lymphoblastic leukemia (B-ALL). Methods We retrospectively analyzed 33 pediatric patients with first-relapsed E/R-positive B-ALL treated at our institution. Overall survival (OS) and cumulative incidence of relapse (CIR) were evaluated. Prognostic factors were identified using Kaplan-Meier methods and Cox proportional hazards models. Results Late relapse (≥ 36 months) occurred in 66.7% of patients. Following re-induction, the secondary complete remission rate was 87.9%, with 54.5% achieving FCM-MRD negativity (< 0.01%). The 5-year OS and CIR for the entire cohort were 66.2% and 45.2%, respectively. Patients achieving FCM-MRD negativity after re-induction had significantly superior 5-year OS compared to those with persistent MRD (83.1% vs. 35.7%, P = 0.003). Although the allo-HSCT cohort had a higher proportion of isolated bone marrow relapses and MRD positivity, multivariate analysis identified post-relapse allo-HSCT ( P = 0.044) and FCM-MRD negativity ( P = 0.005) as independent protective factors for OS. Notably, subgroup analysis revealed that among patients with persistent FCM-MRD positivity, allo-HSCT significantly improved OS compared to non-HSCT consolidation ( P = 0.017). Conclusion FCM-MRD clearance following re-induction is the most critical prognostic determinant for relapsed E/R-positive B-ALL. Allo-HSCT successfully mitigates the extremely high recurrence risk associated with failed MRD clearance. Bridging to allo-HSCT is strongly recommended for relapsed patients exhibiting persistent MRD positivity, as it offers a definitive survival advantage by overcoming chemotherapy resistance.

ObjectivesThis study aimed to investigate the prevalence, pattern of liver involvement at diagnosis of pediatric acute leukemia, and its associations with clinical features and prognosis.MethodsFrom January 2016 to December 2017, 304 consecutive children newly diagnosed with acute leukemia (190 pre-B acute lymphoblastic leukemia (ALL), 25 T-ALL, and 89 acute myeloid leukemia (AML)), were enrolled. Liver involvement was defined as hepatomegaly (HM), hepatocellular injury (HI), hepatic dysfunction (HD) and cholestasis.ResultsThe prevalence of liver involvement varied significantly across leukemia subtypes: T-ALL (80.0%), pre-B-ALL (64.0%), and AML (37.0%) (P<0.001). HM was the most common isolated manifestation in all subtypes. Lower platelet counts were significantly associated with HM and HI in pre-B-ALL, and with HD in T-ALL (all P < 0.05). HI was positively correlated with age in pre-B-ALL (median age: 9.0 vs. 4.0 years, P < 0.001), while HM was associated with higher white blood cell (WBC) counts in T-ALL (228.0 vs. 10×109/L, P = 0.035). HD showed a trend of association with elevated WBC counts in AML (P = 0.054). Liver involvement was not associated with early treatment response or long-term survival in ALL. In AML, however, complex hepatic injury and WBC count emerged as independent adverse prognostic factors: AML patients without liver involvement had the best 5-year overall survival (OS: 87.5 ± 4.4%) and event-free survival (EFS: 80.4 ± 5.3%), whereas those with complex hepatic injury had the poorest outcomes (5-year OS: 58.3 ± 14.2%, EFS:50.0 ± 14.4%).ConclusionsLiver involvement exhibits subtype-specific patterns in pediatric acute leukemia and is associated with age, WBC and platelet counts. Notably, complex hepatic injury may serve as a potential adverse prognostic marker for pediatric AML.

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3. Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher's exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P<0.05 was considered statistically significant. Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK + in 94.1% (16/17) and CD3 + in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m 2 methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2. Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1. Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

To analyze the clinical features of early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in pediatric patients and to summarize the efficacy evaluation of the 2017 protocol by the China Net Childhood Lymphoma (CNCL) Non-Hodgkin Lymphoma (NHL) 2017-LBL for ETP-LBL. Methods Clinical data of 19 children with ETP-LBL admitted to CNCL from May 2017 to August 2023 were retrospectively collected. Results The median age of onset was 10 years (4.5-13 years), including 16 males (84.2%). All patients were in stage IV and were treated with high-risk chemotherapy regimen. 11 of them (57.9%) underwent hematopoietic stem cell transplantation (HSCT). The proportion of leukemia stage in the HSCT group was significantly higher than that in the chemotherapy group (72.7% vs. 25.0%), and the central nervous system (CNS) status was CNS2/3 in the HSCT group (100% vs. 50%).The 3-year overall survival (OS) and event free survival (EFS) were (93.8±0.61) % and (88.2±0.78) %, respectively. Conclusion Over 50% of pediatric ETP-LBL patients received HSCT, with their long-term survival rates comparable to the chemotherapy group.

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive lymphoma that primarily affects children and young adults, and a comprehensive understanding of its molecular features is crucial for improving patient outcomes. In this study, 552 patients were included, with targeted next-generation sequencing of 262 lymphoma-associated genes performed on tumour samples from 119 patients. The associations between mutations and survival rates, as well as relapse and other clinical factors, were analysed. The results demonstrated that pleural effusion (PE) invasion was significantly associated with adverse event-free survival (EFS) and overall survival (OS) (p < 0.05). Additionally, we identified 92 genes with recurrent mutations, among which NOTCH1 (44%), FBXW7 (28%), PHF6 (11%), KRAS (10%) and NRAS (10%) were the most frequently altered. Patients with NOTCH1 mutations exhibited improved EFS and OS (p < 0.01), whereas those carrying CREBBP, PTEN and LYST mutations exhibited worse prognosis (p < 0.05). In conclusion, NOTCH1 mutations are associated with a favourable prognosis in paediatric T-LBL, while CREBBP, PTEN and LYST mutations, as well as PE invasion, are linked to poor prognosis. This study identifies key molecular and clinical factors in paediatric T-LBL progression, aiding high-risk patient identification and personalized treatment strategies.

Background:While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy demonstrates remarkable efficacy in relapsed/refractory (R/R) ALL, its application in earlier treatment lines requires further investigation. This study aimed to evaluate the efficacy, safety, and cellular kinetics of CD19 CAR-T therapy in pediatric B-cell ALL (B-ALL) patients with minimal residual disease (MRD) positivity or chemotherapy intolerance. Methods:Between 2017 and 2021, 50 eligible pediatric B-ALL patients (with positive MRD or chemotherapy intolerance) received CD19 CAR-T therapy. Efficacy endpoints included complete remission (CR), MRD-negative CR (MRD-CR), overall survival (OS), and leukemia-free survival (LFS). CAR-T cellular kinetics parameters (Cmax, AUC0-28d, persistence) were quantified via qPCR and correlated with clinical outcomes. Safety assessment covered cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Results:At day 28 post-infusion, the CR and MRD-CR rates were 98% and 96%, respectively. With a median follow-up of 68.7 months, the 5-year OS and LFS rates were 74.9% and 67.8%. Multivariate analysis identified prolonged B-cell aplasia (BCA) duration (HR = 0.969, p = 0.021) and female sex (HR = 0.235, p = 0.032) as independent protective factors for LFS. Cellular kinetics analysis showed effective in vivo expansion in 98% of patients, with a median Cmax of 30,860 copies/μg DNA and a median time-to-peak of 10.5 days. The MRD-CR group at day 28 exhibited significantly higher Cmax and AUC0-28d (p = 0.017; p = 0.029) and superior CAR-T persistence (p = 0.030) compared to the non-MRD-CR group. Pre-infusion tumor burden levels did not significantly impact CAR-T expansion or duration. BCA duration positively correlated with CAR-T persistence (r=0.570, p < 0.001), but CAR-T expansion parameters (Cmax and AUC0-28d) did not significantly influence BCA. Regarding safety, grade ≥3 CRS occurred in 16% of patients, and ICANS in 10%. Pre-infusion MRD ≥ 10-3 was an independent predictor of severe CRS. Conclusion:CD19 CAR-T therapy demonstrates highly effective MRD clearance and provides long-term survival benefits with a manageable safety profile in pediatric B-ALL patients with MRD positivity or chemotherapy intolerance. Effective CAR-T expansion occurs even at low tumor burdens. These findings support the potential for advancing CAR-T therapy into earlier treatment lines, although its value requires further validation in prospective studies.

INTRODUCTION:This study investigated the efficacy and survival of pediatric refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) treated with a venetoclax (VEN)-based regimen. METHODS:Children with R/R ALL treated with a VEN-based regimen at Peking University People's Hospital from December 1, 2018, to January 15, 2024, were included in this study. Complete remission (CR) or complete remission with incomplete recovery of blood count (CRi) rates and objective response rates (ORRs) were analyzed. RESULTS:Twenty-two children with R/R ALL were included in this study. The median duration of VEN treatment per cycle was 21 (7-28) days, and the median VEN dose was 100 (50-300) mg/day. Following a cycle of VEN-based therapy, 17 children (77.3%) achieved CR/CRi/morphological leukemia-free state (MLFS), including 8 cases (8/17) with negative MRD. The ORR in the children with B-cell acute lymphoblastic leukemia (B-ALL) (n = 9) and T-cell acute lymphoblastic leukemia (T-ALL) (n = 8) was 75% and 80%, respectively. Patients with early T-cell precursor (ETP) ALL (n = 6) achieved MRD-negative remission, and one KMT2A::USP2-positive child achieved MLFS after receiving a VEN-based regimen. For the relapsed patients, the median overall survival (OS) was 1,371 days. For the refractory patients, the median OS was unreached. For T-ALL patients, the median OS was 1,371 days. For the patients with B-ALL, the median OS was 543 days. All patients had hematologic adverse reactions within an acceptable range. CONCLUSION:Children with R/R ALL who received the VEN-based regimen achieved a high remission rate with an acceptable safety profile. Significantly, the VEN-based regimen was effective in patients with R/R ETP with MRD-negative results while also proving beneficial for KMT2A-rearranged, highlighting VEN-chemotherapy as a treatment option for remission.

Erythroblastic sarcoma (ES), the mass-forming presentation of acute erythroid leukemia, is a rare and challenging diagnosis. Given the limited number of published cases, the diagnostic criteria, immunophenotype, and molecular characteristics are not well defined. We describe 56 cases of ES (36 adult and 11 pediatric cases from our cohort, and 9 pediatric cases from the literature). The median age was 60 years among adults and 1.8 years among children. An association with prior cytotoxic therapy or myeloid neoplasm was documented in 10/36 (28%) and 25/36 (69%) adults, respectively, but was not reported in children. Bones were the most common site of involvement among adults (16/36, 44%), whereas soft tissue or central nervous system involvement was most common among children (each 9/20, 45%). Adult and pediatric ES shared similar morphologic features with all cases showing mass formation of erythroblasts and/or involvement of body fluids. Immunophenotypic analysis showed that blasts were positive for CD71 (49/49, 100%), GLUT1 (12/12, 100%), CD43 (37/39, 95%), E-cadherin (38/44, 86%), and CD117 (39/51, 76%) but were mostly negative for CD45 (15/48, 31% positive). Strong and diffuse P53 expression was common among adults (21/24, 88%) and absent among children (3/10, 30% with dim/subset positivity). Although a complex karyotype was common in adult (15/17, 88%) and pediatric ES (8/12, 68%), TP53 mutations were exclusively seen in adult ES (17/19, 89%), at least 11 of which (65%) were biallelic. Instead, pediatric ES was enriched for gene fusions; specific fusions were identified in 10 cases, 7 of which involved NFIA rearrangement. The prognosis was poor among both age groups; 29/37 (78%) patients died from disease with a median overall survival of 3 months. Overall, these results show that adult and pediatric ES have overlapping morphologic and immunophenotypic features but distinct molecular profiles suggesting diverging pathogenesis.