11525 Background: Osteosarcoma is a highly malignant and aggressive tumor, predominantly occurring in children and adolescents under 20 years of age. It exhibits early metastatic potential, with 15%–20% of patients presenting with distant metastasis at diagnosis. Among these, pulmonary metastases account for 85% of cases. The 5-year survival rate after pulmonary metastasis is <20%. This study retrospectively analyzes the efficacy and safety of anlotinib combined with etoposide and ifosfamide in treating pediatric and adolescent patients with pulmonary metastatic osteosarcoma. Methods: This study retrospectively screened children and adolescent patients with pulmonary metastatic osteosarcoma who received etoposide + ifosfamide ± anlotinib at Northwest Women's and Children's Hospital from May 2018 to December 2024. The study was divided into a combination group (anlotinib + etoposide + ifosfamide) and a control group (etoposide + ifosfamide). The dosage of anlotinib: 8 mg for patients < 12 years old, qd, d1-d14, q3w, 12mg for patients ≥12 years old, qd, d1-d14, q3w. Treatment continued until disease progression or intolerable toxicity, with a maximum of 4 chemotherapy cycles. The primary endpoint of the study was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival rate (PFSR), and safety. Results: The data cut-off date was December 2024, The study enrolled 38 patients (combination group: n=18, control group: n=20). Efficacy analysis showed the combination group achieved higher ORR (22.2% vs 15%, p =0.057) and significantly better DCR (66.7% vs 45%, p =0.015), and 3-month progression-free survival rates (PFSR) of 44.0% versus 30%. Subgroup analysis indicated superior outcomes with 12 mg versus 8mg anlotinib ( p <0.05). Biomarker evaluation revealed patients with high BRCA1/VEGFR2 expression had lower 3-year survival than those with intermediate/low expression, while low PDGFR expression was associated with poorer survival compared to intermediate/high levels. The combination group exhibited higher incidence rates of treatment-related adverse events (TRAEs) compared to the control group, including epistaxis (44.4%), hand-foot syndrome (27.8%), abnormal thyroid function (22.2%), and proteinuria (16.7%). All reported adverse events were grade 1-2 in severity, with no grade 3-4 severe adverse reactions observed. Conclusions: The combination therapy of anlotinib with ifosfamide and etoposide demonstrated superior efficacy compared to chemotherapy alone in pediatric patients with pulmonary metastatic osteosarcoma, showing higher ORR, DCR, and 3-month PFSR. These results indicate that anlotinib combined with neoadjuvant chemotherapy can more effectively delay tumor progression and prolong progression-free survival in these patients.

PURPOSEHomoharringtonine (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 METHODSThis 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.RESULTSWe 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).CONCLUSIONHHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

目的 探讨安罗替尼对儿童及青少年骨肉瘤患者化疗后中性粒细胞减少的影响.方法 11例初诊并使用安罗替尼的骨肉瘤患儿为实验组,再按性别、年龄等选取对照组11例,回顾性收集实验组和对照组的临床资料,比较两组患儿中性粒细胞减少的程度、Ⅲ-Ⅳ级中性粒细胞减少的发生率、Ⅳ级中性粒细胞减少的持续时间等.结果 共计217例次化疗中(实验组110例次,对照组107例次),实验组和对照组化疗后中性粒细胞减少的例数无明显差异(P=0.661),实验组Ⅲ-Ⅳ级中性粒细胞减少的发生率较对照组明显升高(P＜0.01),实验组Ⅳ级中性粒细胞减少的持续时间明显增长(P =0.032).结论 安罗替尼可加重骨髓抑制程度,延长重度骨髓抑制时间.

目的 探讨急性淋巴细胞白血病(ALL)患儿儿童肿瘤协作组(CCCG)-ALL 2015方案化疗后早期微小残留病(MRD)检测及与预后的关系.方法 回顾性分析2017年6月—2019年12月收治的ALL患儿102例的临床资料,均采用CCCG-ALL 2015方案化疗,记录化疗后早期MRD发生情况,并探讨其与预后的关系.结果 随访3个月,3组在第15、33天MRD阴性率比较差异无统计学意义(P>0.05),但在第90天,3组间MRD阴性率比较差异有统计学意义(P<0.05).随访3年,102例3年总生存率为90.20％,3年无事件生存率为83.33％.经多因素Logistic回归分析发现,危险度分层高危、白细胞计数>50×109/L、33 d MRD≥1％、90 d MRD≥0.1％是影响ALL患儿3年OS及EFS的独立危险因素(P<0.05).结论 ALL患儿在应用CCCG-ALL2015方案化疗后对MRD进行动态监测十分关键,33 d及90 d MRD水平是提示预后的敏感指标.

e23509 Background: The prognosis of advanced or early advanced osteosarcoma during neoadjuvant chemotherapy is unfavorable. Many patients can only accept brutal amputation without a new and reliable limb rescue solution. There are no clinical data on the efficacy and safety of anlotinib in the treatment of osteosarcoma in children and adolescents. We investigate the efficacy of anotinib plus first-line chemotherapy (platinum + doxorubicin liposome/ifosfamide) in the treatment of early advanced osteosarcoma in children and adolescents. Methods: Early advanced osteosarcoma in this study was defined as pathologically identified osteosarcoma that progressed within 6 months after radical surgery, with neoadjuvant chemotherapy or adjuvant chemotherapy. 11 cases of limb osteosarcoma with Enneking stage IIB (8 cases in the lower femur and 3 cases in the upper tibia), aged 8-15 years, were selected from February 2018 to December 2021. After 1 cycle of first-line neoadjuvant chemotherapy, patients locally advanced received anlotinib (12mg/d) combined with first-line chemotherapy for 1-2 cycles. The tumor shrinkage rate, limb salvage rate, disease-free survival time (DFS), progression-free survival time (PFS), disease control rate (DCR), and safety were analyzed. Results: 9 patients had locally advanced during neoadjuvant chemotherapy. After 2 cycles of anlotinib combined with first-line chemotherapy, the tumor shrunked and was well demarcated from surrounding tissue. All patients underwent limb salvage surgery Postoperative chemotherapy lasted for 4-6 cycles, with a median DFS of 12 months. 2 patients who developed recurrence or metastasis after radical surgery continued to complete at least 8 cycles of standard first-line chemotherapy combined with anlotinib, PFS showed separately 6 months and 8 months. The tumor shrinkage rate was 54.55% and the DCR was 72.73%. The adverse reactions associated with anlotinib were epistaxis (8 cases, 72.72%) and oral ulcer (1 case, 9.09%), which were controlled immediately after withdrawal. Conclusions: Combination of anlotinib with first-line chemotherapy can shrink the tumor, improve limb salvage rate for children with early advanced osteosarcoma, and delay disease progression for children with recurrence and metastasis after radical surgery. The toxicity of anlotinib combined with first-line chemotherapy were tolerated which is expected to be a new approach for the treatment of early advanced osteosarcoma.

Introduction Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancy. Classical induction therapy of DAE composed of etoposide (VP-16), cytarabine arabinoside (Ara-C) and anthracycline (DNR) is commonly applied in childhood AML, but etoposide has been reported to increase the risk of secondary cancer, especially for AML with MLL rearrangement. Although homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML. And whether survival of pediatric AML will benefit from maintenance therapy without increasing toxicity is a matter of debate. All-trans retinoic acid (ATRA)-based therapy has been less reported and verified among non-APL AML patients. Here, we seek to evaluate the efficacy and safety of HHT-based induction regimens combined ATRA-based maintenance therapy for Chinese childhood AML (Chinese Clinical Trial Registry: ChiCTR-IPR-15006816). Methods The 2015 open-label, multicenter, randomized Chinese Children's Leukemia Group (CCLG) study was performed across 35 centers in China between July 2015 and October 2019. Newly diagnosed 0- to 18-year-old children with AML were first randomly assigned to receive HHT-based (H arm) or etoposide-based (E arm) induction regimens [HHT (3 mg/m2 per day from days 1 to 5) or VP-16 (100 mg/m2 per day from days 1 to 5) combined with DA regimen (D: 40 mg/m2 per day on days 1, 3 and 5; A: 100 mg/m2 every 12 hours from day 1 to 7)] and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary endpoint is the complete remission (CR) rate after two courses of induction therapy between H arm and E arm. The secondary endpoints include the 3-year overall survival (OS) and 3-year event-free survival (EFS) of patients in the intent-to-treat population among four arms (H+AT arm, H+AC arm, E+AT arm and E+AC arm). What we should explained is that the study was initially designed as a multicenter randomized controlled trial, however, due to a shortage of HHT, which lasted for half a year in some local hospitals, we had to give priority to ensuring patient benefit and assign these patients to the E arm until HHT became available, and then patients in the H arm were supplemented in those hospitals. So patients were unevenly distributed among the four arms. Results We enrolled 1253 intent-to-treat de novo AML patients, of whom 895 were included in the induction therapy analysis, and 554 received maintenance therapy (Figure 1). The median age was 75.0 months (IQR 36.0-118.0), and 57% of the patients were male. The median follow-up time was 29.4 months (IQR 8.4-47.4). 185 of 1253 patients (14.8%) were lost to follow-up, of whom 70.0% patients have been followed for over 12 months. The CR rates were 88.3% in the H arm versus 83.3% in the E arm (p=0.03). The CR rate of patients with t(8;21)/AML1-ETO was higher in the H arm than in the E arm (94.7% vs. 87.5%, p=0.018). According to the intention-to-treat analysis, the 3-year OS and EFS were significantly higher in the H arm than in the E arm [3-year OS: 69.2% vs. 62.8%, p=0.025 (Figure 2); 3-year EFS 61.1% vs. 53.4%, p=0.022]. Among patients who were enrolled in maintenance therapy (per-protocol population), the 3-year EFS (H+AT arm: 70.7%, 95% CI 61.1-78.3; H+AC arm: 74.8%, 95% CI 67.0-81.0, p=0.933; E+AC arm: 72.9%, 95% CI 65.1-79.2, p=0.789; E+AT arm: 66.2%, 95% CI 56.8-74.0, p=0.336) did not differ significantly across the four arms. In subgroup analysis, patients with AML1-ETO positivity in the H+AT arm had significantly better OS (82.4% vs. 66.4%, p=0.043) and EFS (73.6% vs. 52.8%, p=0.013) than those in the E+AC arm. Conclusions Our study demonstrated, in childhood AML, HHT-based induction regimens (DAH) could significantly obtain higher complete remission rate compared with patients who received etoposide-based regimens, especially for those with AML1-ETO positive. And The HTT-based regimen resulted in a significantly improved 3-year OS and EFS compared with VP-16-based regimen. More patients with AML1-ETO positive who took DAH achieved complete remission, and these patients had longer overall survival and event-free survival, than those who took DAE. And ATRA-based maintenance has comparable effects to cytarabine-based maintenance in terms of OS and EFS. ATRA may be an alternative option for pediatric AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

目的 分析大剂量甲氨蝶呤(HD-MTX)的不同起始剂量治疗儿童急性淋巴细胞白血病(ALL)的毒副反应.方法 回顾性选取2015年4月到2019年5月本院收治的60例ALL患儿作为研究对象,根据CCCG-ALL-2015方案,将其分为低危组(28例)和中高危组(32例).在行VDLP和CAM化疗后,根据Ccr调节起始MTX的剂量,足量应用为中高危组给予5 g/m2,低危组给予3 g/m2.比较不同MTX治疗剂量下患儿排泄延迟及素毒副反应的发生情况.结果 足量用药组排泄延迟人数占比高于其他剂量组.中高危组排泄延迟发生率高于低危组(P<0.05).排泄延迟组毒副反应发生率均高于排泄正常组(P<0.05).结论 MTX使用剂量越大,延迟排泄及毒副反应发生率越高.

目的 总结我科10例婴儿急性淋巴细胞白血病(IALL)临床及实验室特点,探讨其治疗及预后的相关因素.方法 回顾性分析2014年12月至2020年10月我院收治的10例IALL患儿的临床表现、实验室检查结果、治疗及预后情况.结果 10例患儿中,2例为高危,8例为中危.在诱导治疗I评估点时,有6例患儿微小残留病(MRD)<0.01％,缓解率为60.0％;在诱导治疗Ⅱ评估点时,4号患儿因化疗并发症死亡,剩余9例患儿MRD<0.01％,缓解率为90.0％;1号患儿于规律化疗1.5年后,在进行维持治疗时复发,放弃治疗后死亡;余8例患儿均存活至今,存活时间最长46个月,最短5个月.结论 IALL为罕见病例,发病率低,因其特殊的生物学特征,预后差.本研究中1号患儿缓解后复发,4号患儿因化疗并发症死亡,8例存活至今.

目的:探讨陕西省商州区0～6岁儿童缺铁性贫血(IDA)患病现状及发病相关风险因素.方法:选取陕西省商州区2215例0～6岁儿童作为研究对象,通过问卷调查、常规体格检查,以及血常规、血清铁、铁蛋白含量检测和流行病学数据(孕周、出生体重、喂养情况、家庭收入等)采集,分析IDA发生的影响因素.结果:2215例0～6岁学龄前儿童IDA发病率为19.86％,其中6月龄至1岁为IDA高发年龄阶段.商州区0～6岁儿童IDA发生的影响因素有家庭收入、出生体重、辅食添加时间、饮食偏好、喂养方式及母孕期是否贫血;IDA发生的独立危险因素包括母亲生育年龄、家庭收入、出生体重、喂养方式及母孕期贫血(均P<0.05).结论:陕西省商州区0～6岁儿童IDA患病率仍处于较高水平,需加强母孕期健康宣教,提高家庭收入,积极母乳喂养,按时添加辅食,以降低该地区0～6岁儿童IDA患病率,提高儿童健康水平.