摘要目的:探讨急性未分化白血病(AUL)的临床特点、诊断与治疗方法，并进行相关文献复习。方法:选择2020年8月24日、2021年7月20日威海市立医院收治的2例AUL患者为研究对象。根据2例患者入院时间，将其依次编号为患者1、2。患者1～2均为男性，年龄分别为62、76岁。采用回顾性分析方法，收集其临床病例资料，包括临床特征及外周血常规、生化、凝血、骨髓细胞形态学、骨髓细胞免疫分型检查结果，诊断、治疗及预后。根据患者1～2临床症状及实验室检查结果，对其进行诊断及治疗。对患者1～2的随访分别截至2020年10月31日与2021年9月30日。本研究以"急性未分化白血病""系列不明急性白血病""急性髓细胞白血病""急性髓细胞白血病微分化型""acute undifferentiated leukemia""acute leukemia of ambiguous lineage""acute myeloid leukemia""acute myeloid leukemia with minimal differentiation""AUL""ALAL""AML"为中、英文关键词，检索中国知网数据库、万方数据知识服务平台和PubMed数据库中AUL相关文献，总结与本研究患者1～2相关的诊疗资料。文献检索时间为上述数据库建库至2022年8月30日。本研究获得威海市立医院伦理委员会审批(批准文号：2023042)，并与患者签署临床研究知情同意书。结果:①患者1因"乏力2个月，发热2 d，伴胸闷、憋气1 d"入本院治疗，患者1既往有"2型糖尿病"病史；曾于当地医院就诊，疗效不佳，遂转入本院进一步治疗。患者2因"发现颈部右侧肿物10 ＋ d"入本院治疗，同时右侧颈部疼痛，转颈吞咽时加重，伴发热，偶有胸闷、憋气，伴咳嗽；无其他疾病史和家族史。②入院后，患者1相关检查结果示，白细胞计数(WBC)为108.34×10 9/L，红细胞计数为2.86×10 12/L，血红蛋白(Hb)值为92 g/L，血小板计数为7×10 9/L；B型钠尿肽前体、降钙素原、C反应蛋白水平进行性升高；骨髓细胞形态学检查结果示，原始细胞比例为97.00%；骨髓细胞免疫分型结果示，异常原始细胞占有核细胞比例为98.12%，表达CD34、CD38、CD13、CD123，部分表达CD9，弱表达人类白细胞抗原(HLA)-DR，除表达CD13外，不表达其他髓系、B系和T系相关和特异性抗原。患者2相关检查结果示，WBC为18.05×10 9/L，红细胞计数为4.88×10 12/L，Hb值为141 g/L，血小板计数为49×10 9/L；C反应蛋白值升高；骨髓细胞形态学检查结果示，粒系原始细胞比例为84.00%；骨髓细胞免疫分型结果示，异常原始细胞占有核细胞比例为87.55%，表达CD7、CD38、CD99，小部分表达HLA-DR，部分表达CD34、CD33、CD123，小部分表达cCD3(阳性率为3.87%，细胞质抗体阳性率<10.00%)，其余相关抗原均不表达。③患者1于2020年8月27日被诊断为AUL，遂于9月1日对其采取VDCP[长春新碱1.5 mg/(m 2·d)，d1～8＋柔红霉素45 mg/(m 2·d)，d1～3＋环磷酰胺750 mg/(m 2·d)，d1＋泼尼松1 mg/(kg·d)，d1～4、8～11]方案化疗，28 d为1个疗程。其接受2个疗程VDCP方案化疗后，由于年龄大且基础疾病较重，病情迅速复发恶化，患者家属放弃治疗。患者1出院后，血小板计数呈下降趋势，并于2020年10月10日合并严重感染死亡。患者2于2021年7月28日被诊断为AUL。由于患者2年龄大，遂于7月30日对其采取减低剂量VAP[长春新碱1.5 mg/(m 2·d)，d1～8＋阿糖胞苷100 mg/(m 2·d)，d1～6＋泼尼松1 mg/(kg·d)，d1～7]方案化疗，28 d为1个疗程。其接受1个疗程减低剂量VAP方案化疗后，疗效较差，家属放弃治疗。患者2出院后，病情恶化严重，并于2021年9月10日大出血死亡。④根据文献检索策略，共纳入6篇报道8例AUL患者相关文献，加上本研究患者1～2共10例AUL患者。对这10例患者的研究结果显示，>60岁患者为4例，9例患者无合并症，4例患者初诊时伴淋巴结大，2例接受造血干细胞移植(HSCT)后缓解，1例接受DAVP(柔红霉素＋阿糖胞苷＋长春新碱＋泼尼松)方案化疗后缓解，1例接受CAVD(环磷酰胺＋阿糖胞苷＋长春新碱＋柔红霉素)方案化疗后缓解，1例接受DA(柔红霉素＋阿糖胞苷)＋依维替尼方案化疗后缓解，5例患者死亡。 结论:AUL患者临床少见，该病以急性髓细胞白血病(AML)的临床表现为主，诊断主要依据骨髓细胞形态学与免疫分型检查，目前尚无统一治疗方案，患者预后较差。

abstractsObjective:To investigate the clinical features, diagnosis and treatment of acute undifferentiated leukemia (AUL), and review relevant literature.Methods:On August 24, 2020 and July 20, 2021, 2 patients with AUL admitted to Weihai Municipal Hospital were selected as study subjects, and numbered as patient 1 and 2 according to the time of admission. These 2 male patients were aged 62 and 76 years, respectively. A retrospective study was conducted to collect clinical data of 2 patients, including clinical features, peripheral blood routine examination, biochemical and coagulation examination, bone marrow cell morphology examination, bone marrow immune typing examination, diagnosis, treatment and prognosis. According to the clinical symptoms and laboratory results, the patients were diagnosed and treated. Patient 1 and 2 in the study were followed up until October 31, 2020 and September 30, 2021, respectively. China National Knowledge Infrastructure database, Wanfang Data Knowledge Service platform and PubMed database were searched using " acute undifferentiated leukemia" " acute leukemia of ambiguous lineage" " acute myeloid leukemia" " acute myeloid leukemia with minimal differentiation" " AUL" " ALAL" and " AML" as keywords in Chinese and English. Related literature were summarized and reviewed. Literature search period was from the establishment of the database to August 30, 2022. This study was approved by the Ethics Committee of Weihai Municipal Hospital (Approval No. 2023042)and clinical research informed consent was signed with the patients.Results:① Patient 1 was admitted due to " fatigue for 2 months, fever for 2 d, and chest tightness and suffocation for 1 d". Patient 1 had a history of type 2 diabetes. He was treated in a local hospital, but the effect was not well, so he was transferred to our hospital for further treatment. Patient 2 was admitted due to " the tumor which was found on the right side of the neck for 10 + d", which was aggravated when the neck was swallowed, accompanied by fever, occasional chest tightness, suffrage and cough. ② After admission, related examination results of patient 1 showed, white blood cell count (WBC) was 108.34×10 9/L, red blood cell count was 2.86×10 12/L, hemoglobin (Hb) was 92 g/L, and platelet count was 7×10 9/L. B-type natriuretic peptide precursor, procalcitonin and C-reactive protein were increased progressively. Results of bone marrow cell morphology showed primitive cells accounted for 97.00%. Bone marrow immunotyping results showed that abnormal primitive cells accounted for 98.12% of the nuclear cells, these cells expressed CD34, CD38, CD13, CD123, partially expressed CD9, weakly expressed human leukocyte antigen (HLA)-DR, and did not express other myeloid, B-line or T-line related and specific antigens except CD13. Related examination results of patient 2 showed WBC was 18.05×10 9/L, red blood cell count was 4.88×10 12/L, Hb value was 141 g/L, and platelet count was 49×10 9/L. Value of C-reactive protein was high. Results of bone marrow cell morphology showed that the proportion of myeloid blast cells was 84.00%. Bone marrow immunotyping showed that abnormal primitive cells accounted for 87.55% of nuclear cells, expressing CD7, CD38 and CD99, a small part expressed HLA-DR, partially expressed CD34, CD33, CD123, and a small part of cCD3 (positive rate was 3.87%, cytoplasmic antibody positive rate<10.00%), and the remaining series of related antigens were not expressed. ③ Patient 1 was diagnosed as AUL on August 27, 2020, and received VDCP (vincristine+ daunorubicin+ cyclophosphamide+ prednisone) regimen on September 1. Specific regimen was vincristine 1.5 mg/ (m 2·d), d1-8; daunorubicin 45 mg/ (m 2·d), d1-3; cyclophosphamide 750 mg/ (m 2·d), d1; prednisone 1 mg/ (kg·d), d1-4, 8-11. And 28 d was 1 course of treatment. After 2 courses of VDAP chemotherapy regimens, due to the older age of patient 1 and the severity of the underlying disease, the disease quickly recurred and worsened. His family members gave up treatment. After discharge, the platelet count showed a decreasing trend, and patient 1 died due to severe infection on October 10, 2020. Patient 2 was diagnosed as AUL on July 28, 2021 and received low-dose VAP (vincristine+ cytarabine+ prednisone) regimen on July 30 due to older age. Specific regimen was vincristine 1.5 mg/ (m 2·d), d1-8; cytarabine 100 mg/ (m 2·d), d1-6; prednisone 1 mg/ (kg·d), d1-7. And 28 d was 1 course of treatment. After 1 course of low-dose VAP regimen, patient′s the effect was poor, so his family members gave up on continuing treatment. After discharge, the condition of the patient deteriorated seriously. The patient died due to massive bleeding on September 10, 2021. ④ According to the literature search strategy, 6 related articles with 8 AUL patients were searched, and a total of 10 AUL patients were involved including patient 1 and 2 in this study. Results of literature review showed that there were 4 patients over 60 years old, 9 patients with no complications, 4 patients with large lymph nodes at first diagnosis, 2 patients in remission after hematopoietic stem cell transplantation (HSCT), 1 case in remission after DAVP (daunorubicin+ cytarabine+ vincristine+ prednisone) chemotherapy regimen, 1 case in remission after CAVD (cyclophosphamide+ cytarabine+ vincristine+ daunorubicin) chemotherapy regimen, 1 case in remission after DA (daunorubicin+ cytarabine)+ ivosidenib chemotherapy regimen, and 5 patients died. Conclusions:AUL is a rare clinical disease, mainly characterized by acute myeloid leukemia (AML), and the diagnosis is mainly based on bone marrow cell morphology and immunophenotyping. There is no unified treatment plan for AUL patients and their prognosis are very poor.