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.

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.

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.

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.

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%, 𝑥 2 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.

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.

背景 以周围性面瘫起病的儿童急性白血病国内外相关报道较少,临床易被误诊.目的 探讨以周围性面瘫为首发症状的急性白血病患儿的临床特点、治疗和预后.设计病例系列报告.方法 纳入2010年1月至2021年9月北京大学人民医院儿科收治的以周围性面瘫为首发症状的急性白血病患儿,分析其临床特征、辅助检查、治疗和预后.主要结局指标面瘫结局以及5年无事件生存(EFS)、总生存(OS).结果 研究期间共收治急性白血病患儿1018例,其中ALL 728例,AML 290例.16例(1.6％)患儿以周围性面瘫为首发症状起病,其中男7例、女9例,中位年龄5(2～14)岁,从面瘫起病至确诊白血病中位时间9.5(1～31)d;其中ALL B细胞型2例(12.5％),ALL T细胞型1例(6.2％),AML M2型13例(81.3％).16例均为单侧面瘫,左侧5例(31.2％),右侧11例(68.8％).15例行头颅MR检查,2例示硬脑膜、软脑膜增厚强化(其中1例伴面神经可疑损伤),1例示眼内直肌及视神经眶内段白血病浸润,3例示乳突炎.15例行脑脊液检查,其中1例脑脊液残留阳性,1例曾出现脑脊液蛋白升高.1例确诊白血病后放弃治疗,余15例予以化疗.8例规律化疗后骨髓持续缓解,6例行造血干细胞移植,1例化疗期间因合并多脏器功能不全而停止化疗,复发后死亡.13例在1个月内面瘫症状消失,2例在3个月内面瘫症状消失.中位随访时间44.5(0.23～111)月,5年EFS为(48.2±13.0)％,5年OS为(87.5±8.3)％.13例AML患儿5年EFS为(51.3±14.6)％,5年OS为(84.6±10.0)％,其中造血干细胞移植患儿5年OS为100％,仅化疗患儿5年OS为(87.5±11.7)％,差异无统计学意义(P=0.48).结论 以周围性面瘫为首发症状的急性白血病患儿早期易被误诊.对于儿童周围性面瘫,在类固醇激素治疗前应排除继发性病因.以面瘫起病的急性白血病类型以AML为主,需考虑强化中枢神经系统治疗.周围性面瘫起病的AML患儿总体生存率无明显影响,但更易复发.

The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.

目的 总结儿童门冬酰胺酶(Asp)相关性胰腺炎(AAP)的临床特征及预后.方法 纳入2012年1月至2019年12月初诊并接受Asp联合化疗后出现急性胰腺炎的21例急性淋巴细胞白血病(ALL)患儿,分析其临床特征、实验室检查、治疗情况和预后.结果 研究期间初诊并接受Asp治疗的ALL患儿共711例,21例患儿发生AAP,发生率为3.0％.21例患儿中,男10例、女11例,中位年龄8岁(3～18岁);7例AAP发生于诱导化疗期,L-asp中位次数7次(1～10次);14例发生于巩固化疗期,PEG-asp治疗后16.5天(2～22天),中位次数4.5次(1～9次).轻型AAP 14例,重型7例;腹痛、呕吐为最常见的症状.AAP诊断时,血清淀粉酶和脂肪酶中位数分别为471 U/L(范围25～1632 U/L)和287.1 U/L(范围4.6～2213.7 U/L).13例患儿行腹部超声,6例(46.2％)阳性;20例行腹部CT,17例(85.0％)阳性.4例AAP患儿出现胰腺假性囊肿.所有患儿均在早期予禁食、抑酸、抑制胰酶分泌、营养支持等治疗,3例采用经鼻空肠管喂养,5例行手术干预.4例轻型AAP患儿再次使用L-asp化疗,其中1例再发AAP.末次随访时,除1例患儿放弃治疗外,无胰腺炎相关死亡病例,1例发生慢性胰腺炎,其余19例胰腺炎已愈.结论 AAP是Asp治疗过程中的严重并发症,早期识别是关键,总体预后良好.

背景 儿童复发/难治性急性淋巴细胞白血病(ALL)临床治疗较困难、预后差.硼替佐米联合化疗显示出一定的有效性,目前国内相关报道较少.目的 探讨硼替佐米联合化疗对复发难治及高危儿童ALL的疗效及安全性.设计病例系列报告.方法 纳入2017年9月至2019年9月北京大学人民医院儿科收治的接受硼替佐米联合化疗的复发难治及高危ALL患儿,分析其临床特征、实验室检查、治疗情况和预后.主要结局指标总反应率(ORR)、2年无事件生存(EFS)、总生存(OS)、不良反应.结果 11例患儿纳入分析,男9例,女2例,诊断中位年龄10(3～15)岁.7例T-ALL,2例T淋巴母细胞淋巴瘤Ⅳ期,2例B-ALL.复发2例,难治4例,高危5例.经硼替佐米联合化疗1个疗程后,8例(B-ALL 1例,T-ALL 7例)治疗有反应,ORR 72.7％.治疗前骨髓形态未缓解3例,部分缓解4例,治疗后完全缓解率85.7％(6/7);治疗前骨髓微小残留病(MRD)阳性10例,治疗后均有下降,其中1例MRD转阴.不良反应总体可耐受,主要为骨髓抑制、感染、胃肠道反应、肝功能异常等,无化疗相关死亡病例.9例行异基因造血干细胞移植治疗,其中7例无病存活,2例死于移植后复发;2例患儿继续化疗,长期随访均死亡.中位随访时间15(2～29)个月,2年EFS为(45.5±15)％,OS为(63.6±14.5)％.结论 硼替佐米联合化疗是复发难治及高危ALL患儿的一种有效、耐受性良好的治疗选择.

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 ofRUNX1/RUNX1T1transcripts 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.

患儿女,12岁,因“间断发热伴乏力2周余”于2016年8月26日入院.患儿足月经阴道分娩,出生史无异常.家族史:患儿父母非近亲婚配史,父亲体健,母亲因甲状腺肿大行右侧甲状腺部分切除术,患儿外公有多发甲状腺结节,后因淋巴瘤(具体类型不详)病逝,患儿有1弟弟,体健.既往史:2岁时出现听力进行性下降,诊断为双侧感音神经性耳聋,佩戴助听器.6岁时左耳听力降为97 dBHL,右耳为85 dBHL,颞骨CT扫描显示前庭导水管增大(enlarged vestibular aqueduct,EVA).遂行人工耳蜗植入治疗后至今.7岁时被发现有多发甲状腺结节,每年检查甲状腺功能均正常,故未治疗.对患儿及其弟弟、父母抽取外周血进行医学全外显子基因检测,该患儿基因为来自父亲c.1174A＞ T(p.N392Y)和母亲c.2168A＞G(p.H723R)的杂合变异,见图1,患儿弟弟结果无变异.确诊为Pendred综合征(PDS).

目的:探讨形成性评估在综合医院儿科技能训练教学中的作用.方法:在儿科见习技能训练中,将43名八年制医学生随机分成实验组和对照组,在临床技能操作训练中,对照组22名学生采用实时纠错终结性评估教学方法,实验组21名学生采用回放纠错形成性评估教学法.教学结束后进行客观结构化临床考试,统计分析两组学生成绩,并调查实验组学生对回放纠错形成性评估的认可程度.结果:实验组学生的客观结构化临床考试的得分均高于对照组学生,差异具有统计学意义.大多数实验组学生对该教学评估方法予以肯定.结论:在八年制医学生儿科见习技能训练中,引入回放纠错形成性评估可提高学生的技能操作能力,适合应用.

通过问卷调查方式,了解学生对儿童白血病教学内容的了解程度、学习中的重点及难点、对现有教学方式的满意程度、期望的教学方式等情况,提出构建典型病例、开展病案讨论式教学、联系基础医学内容、扩展教学内容、应用高仿真模拟装置等改善教学的策略.

Objective To investigate the correlation between hypoglycemia and brain injury of newborns.Methods Medical records and follow-up data of 110 newborns with hypoglycemia (blood glucose level≤2.2 mmol/L) who admitted into neonatal department of Peking University First Hospital from December 2006 to December 2009 were studied.All patients were divided into 3 groups:no brain injury group,mild and severe brain injury group according to their clinical manifestation,cerebral radiological characteristics and cerebral functional tests.By using receiver operating characteristic (ROC) curve and x2 test,the potential optimal blood glucose level and duration of hypoglycemia for predicting brain injury were confirmed.Multivariate Logistic regression was taken to determine independent predictors for brain injury.The analyzed factors included gender,preterm/small for gestational age,hyperbillirubinemia,fetal distress,asphyxia,infection,seizures and maternal hypertensive disorder complicating pregnancy and hyperglycemia.Results Among the 110 hypoglycemia newborns,33 (30.0％) infants suffered from brain injury,of which 23 were mild and 10 were severe.Blood glucose ≤1.7 mmol/L had high specificity (73％) and sensitivity (60％)for predicting brain injury.When blood glucose≤ 1.7 mmol/L,the incidence of brain injury and severe brain injury was 43.6％ (24/55) and 18.2％ (10/55),which was higher than those [16.4％(9/55) and 0.0％ (0/55)] of patients whose glucose level ＞1.7 mmol/L(x2 =9.74 and 11.00,P＜0.01 respectively).Blood glucose ≤ 1.2 mmol/L had high specificity (100％) and sensitivity (81％) for predicting severe brain injury.When blood glucose ≤1.2 mmol/L,the incidence of severe brain injury was higher than that of the patients whose glucose level was higher than 1.2 mmol/L [34.5％ (10/29) vs 0.0％ (0/81),x2 =30.72,P＜0.01].Duration of hypoglycemia ≥12 h had specificity (100％) and sensitivity (36 ％) for predicting brain injury.When duration of hypoglycemia ＜12 h,the incidence of brain injury was lower than that of the patients whose duration of hypoglycemia≥12 h [21.4％ (21/98) vs 6/6,x2 =27.69,P＜0.01].Multivariate Logistic regression showed that fetal distress (OR=4.69,95％CI:1.47-14.97,P=0.009),glucose level≤1.2 mmol/L (OR =5.16,95％CI:1.56-17.03,P=0.007),duration of hypoglycemia≥12 h (OR=8 885 220 297.12,95％CI:0.00-∞,P =0.000) and maternal hyperglycemia (OR =3.34,95％CI:1.01-11.02,P=0.048) were independent risk factors for neonatal brain injury.Conclusions Low blood glucose level and prolonged hypoglycemia might induce injury of neurol system.Fetal distress and maternal hyperglycemia might increase the incidence of brain injury in newborns with hypoglycemia.

新生儿血糖检查开始于:1910年,1937年Hartmann和Jaudon首次提出低血糖是新生儿常见疾病,该病开始受到关注.低血糖带来的最大危害是造成神经系统损伤,1959年Cornblath和助手首先提出低血糖可致严重神经系统后遗症.