Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.
目的： 分析儿童伯基特淋巴瘤（BL）化疗延迟的影响因素及其对预后的影响。 方法： 回顾性队列研究。收集中国儿童淋巴瘤协作组（CNCL）2017年5月至2022年12月收治的591例年龄≤18岁BL患儿临床资料，治疗均采用CNCL-BL-2017方案。依据临床特征，治疗方案分为A组、B组、C组。根据化疗总时间是否延迟分为化疗延迟组和非化疗延迟组。治疗方案C组患儿根据化疗总延迟时间分为非延迟组、1~7 d化疗延迟组和>7 d化疗延迟组。分析化疗延迟与性别、年龄、化疗前合并肿瘤溶解综合征、骨髓受累、治疗分组、血清乳酸脱氢酶（LDH）>正常4倍、化疗后合并Ⅲ~Ⅳ级骨髓抑制、中期评估有残留、重症感染（包括重症肺炎、败血症、脑膜炎、水痘等）等因素的关系。应用Logistic回归分析影响化疗延迟的因素，采用Kaplan-Meier及Log-Rank检验绘制生存曲线并组间比较。 结果： 591例患儿中男504例、女87例，随访时间34.8（18.6，50.1）个月，3年总生存率（OS）为（92.5±1.1）%，3年无事件生存率（EFS）为（90.5±1.2）%。化疗延迟组73例（12.4%），非化疗延迟组518例（87.6%）。化疗延迟的原因包含重症感染72例（98.6%）、骨髓抑制65例（89.0%）、脏器功能损伤35例（47.9%）、肿瘤溶解综合征22例（30.1%）等。治疗方案B组7例化疗延迟中COPADM（长春新碱+环磷酰胺+泼尼松+柔红霉素+甲氨蝶呤+鞘内注射）阶段4例，CYM（甲氨蝶呤+阿糖胞苷+鞘内注射）阶段3例，治疗方案C组66例化疗延迟常见于COPADM（28例）和CYVE1（小剂量阿糖胞苷+大剂量阿糖胞苷+依托泊苷+甲氨蝶呤，12例）两阶段。多因素Logistic回归分析显示年龄>10岁（OR=0.54，95%CI 0.30~0.93）、化疗前合并肿瘤溶解综合征（OR=0.48，95%CI 0.27~0.84）、化疗后合并Ⅲ~Ⅳ级骨髓抑制（OR=0.55，95%CI 0.33~0.91）为化疗延迟的独立危险因素。化疗延迟组患儿3年OS、EFS均低于非化疗延迟组［（79.4±4.9）%比（94.2±1.1）%，（80.2±4.8）%比（92.0±1.2）%，均P<0.05］。治疗方案C组患儿>7 d化疗延迟组（42例）的3年OS低于1~7 d化疗延迟组（22例）、非化疗延迟组（399例）［（76.7±6.9）%比（81.8±8.2）%比（92.7±1.3）%，P=0.002］。治疗方案C组患儿中COP（长春新碱+环磷酰胺+泼尼松）阶段化疗延迟组（9例）3年OS低于非化疗延迟组（454例）［（66.7±15.7）%比（91.3±1.4）%，P=0.005］。COPADM1阶段化疗延迟组（11例）3年OS低于非化疗延迟组（452例）［（63.6±14.5）%比（91.5±1.3）%，P=0.001］。 结论： 儿童BL诊治过程中，化疗延迟与年龄>10岁、化疗前合并肿瘤溶解综合征、化疗后合并Ⅲ~Ⅳ级骨髓抑制有关，一旦发生化疗延迟，影响疾病预后。.