【摘要】 目的:分析伴PAX5 P80R突变的急性B淋巴细胞白血病(B-ALL)的临床和分子遗传学特征，探索该亚型患者治疗方案与预后的关系。方法:回顾性研究2019年9月—2024年11月苏州大学附属第一医院和苏州弘慈血液病医院收治的B-ALL患者中，伴PAX5 P80R突变患者的临床资料。结果:936例B-ALL患者中，10例(1.1%)伴PAX5 P80R。其中，男性占80%,初诊中位年龄为35.5(14.0～59.0)岁。10例患者均表达CD10、CD19,其中7例患者还表达CD34和CD38。4例患者合并染色体异常，所有患者融合基因均阴性。7例患者合并22个共突变，其中NRAS最为常见(5/7)。异常核型患者伴有2个以上共突变比例明显高于正常核型患者(100.0%vs 16.6%,P=0.02)。经过基于VP(长春地辛+地塞米松)方案的多药联合诱导化疗后，10例患者均达到形态学完全缓解(CR),其中5例(50%)流式微小残留病(MFC-MRD)阴性(<0.01%);巩固治疗期间，4例在CR1期间行异基因造血干细胞移植(allo-HSCT)的患者存活，3例患者化疗期间出现复发(2例死亡，1例经移植、嵌合抗原受体T细胞治疗后存活),2例化疗患者无复发生存[1例儿童患者已完成中国儿童白血病协作组-2015化疗方案(CCCG-ALL-2015),1例拟行allo-HSCT],其余1例患者失访。中位随访时间42(2～63)个月，5年总生存率(OS)及无复发生存率(PFS)分别为75%(95%CI 0.153～0.503)和62.5%(95%CI 0.171～0.365),中位OS和PFS均未达到。结论:PAX5 P80R突变的B-ALL对诱导化疗敏感，总体预后良好，但合并其他高危遗传学异常对预后的影响有待进一步探索。更多还原

【Abstract】 Objective: To analyze the clinical and molecular genetic features of B-cell acute lymphoblastic leukemia(B-ALL) with PAX5 P80R and explore the correlation between treatment approaches and clinical outcomes. Methods: A retrospective study was conducted on clinical data of B-ALL patients with PAX5 P80R mutation admitted to the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital from September 2019 to November 2024. Results: In a cohort of 936 patients diagnosed with B-ALL, 10 cases(1.1%) were identified PAX5 P80R mutation. Among these cases, 80% were male, with a median age of 35.5 years at diagnosis(range 14-59 years). All 10 patients expressed CD10 and CD19, with 7 of them also expressing CD34 and CD38. Four patients had chromosomal abnormalities, while all patients tested negative for fusion genes. Seven patients had 22 co-mutations, with NRAS being the most common(5/7). The proportion of patients with more than two co-mutations was significantly higher in those with abnormal karyotypes compared to those with normal karyotypes(100.0% vs 16.6%, P=0.02). Following induction chemotherapy based with VP regimen, all patients achieved complete remission(CR), with a 50% rate of minimal residual disease(MRD) negativity by flow cytometry. During consolidation therapy, 4 patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT) in CR1. Of the remaining patients, 3 experienced relapse(2 deaths, 1 survived after allo-HSCT and chimeric antigen receptor T cell therapy), while 2 were still alive without recurrence(1 pediatric patient completed the CCCG-ALL-2015 protocol, and 1 was planning for allo-HSCT). One patient was lost to follow-up. The median follow-up was 42 months(range 2-63 months), with 5-year overall survival(OS) and progression-free survival(PFS) rates of 75%(95%CI 0.153-0.503) and 62.5%(95%CI 0.171-0.365), respectively. The median OS and PFS were not reached. Conclusion: B-ALL with PAX5 P80R shows positive responses to induction chemotherapy, with an overall good prognosis. However, the impact of concomitant high-risk genetic abnormalities on prognosis remains to be further explored.更多还原