急性混合细胞白血病24例临床和生物学特征

Clinical and biological features of mixed-phenotype acute leukemia:an analysis of 24 cases

目的探讨急性混合细胞白血病(MPAL)的临床和生物学特征.方法回顾性分析福建医科大学附属协和医院2012年1月至2018年10月收治的24例初治MPAL患者的临床资料,所有患者均满足世界卫生组织(WHO)2016诊断标准.通过形态学及细胞化学染色、免疫分型、细胞遗传学、分子生物学检测,分析患者临床和生物学特征.结果24例患者中,男性16例,女性8例,中位年龄27岁(5~66岁);骨髓幼稚细胞占有核细胞(57.41±23.20)%;13例(54.2%)形态学诊断为MPAL,5例(20.8%)为急性髓系白血病(AML),5例(20.8%)为急性淋巴细胞白血病(ALL),1例(4.2%)分型不明.24例免疫分型检查均诊断为MPAL,其中18例(75.0%)表达髓系和B系抗原,5例(20.8%)表达髓系和T系抗原,1例(4.2%)表达T、B系抗原;CD38、HLA﹣DR和CD34阳性率分别为90.5%(0.1%~99.7%)、90.1%(1.1%~98.8%)和81.3%(0.1%~97.8%).18例行染色体检查,其中5例伴t(9;22)(q34;q11),3例伴t(v;11q23.3),2例合并复杂核型,2例合并t(9;22)(q34;q11)和复杂核型.21例行基因检查,其中6例BCR﹣ABL阳性,3例MLL阳性,1例MLL和BCR﹣ABL阳性,1例BCR﹣ABL和TP53阳性,1例PHF6和ASXL1阳性.24例中,7例拒绝化疗,17例接受诱导化疗;接受化疗者中,9例完全缓解(CR),1例部分缓解(PR),7例未缓解(NR);淋系方案治疗组11例和兼顾淋系、髓系方案治疗组6例中,达CR者分别有8例和1例,CR率差异有统计学意义(P<0.05);费城染色体(Ph)阳性6例和Ph阴性组11例中,达CR者分别有1例和8例,CR率差异有统计学意义(P<0.05).24例MPAL患者中位随访时间为5.5个月(0~36个月),3年总生存(OS)率为17.5%,中位OS时间为6个月.异基因造血干细胞移植和未移植组3年OS率分别为75.2%和0,中位OS时间分别为未达到和4个月(P<0.05).结论MPAL较罕见,以髓系和淋系抗原共表达为主,CD38、CD34、HLA﹣DR阳性率高,常伴Ph阳性和复杂核型.MPAL缓解率低,预后差,应进一步探讨合理有效的治疗方案.

Objective To investigate the clinical and biological features of patients with mixed-phenotype acute leukemia(MPAL).Methods The clinical data of 24 de novo adult patients with MPAL who were admitted to Fujian Medical University Union Hospital from January 2012 to October 2018 were retrospectively analyzed.These patients were diagnosed according to the World Health Organization(WHO)2016 criteria.The clinical and biological characteristics of the patients were analyzed by morphological and cytochemical staining,immunophenotyping,cytogenetics and molecular biology.Results Of the 24 patients,16 were male and 8 were female,and the median age of the patients at diagnosis was 27 years old(5-66 years old).The average blasts of bone marrow were(57.41±23.20)%.Thirteen cases(54.2%)were diagnosed as MPAL morphologically,while 5 cases(20.8%)were diagnosed as acute myeloid leukemia(AML),5 cases(20.8%)were diagnosed as acute lymphoblastic leukemia(ALL)and 1 case(4.2%)was inconclusive.Eighteen patients(75.0%)co-expressed B-lymphoid and myeloid markers,while 5 patients(20.8%)with T-lymphoid and myeloid markers and 1 patient(4.2%)with B-lymphoid and T-lymphoid markers,respectively.The positive rate[median(range)]of CD38,HLA-DR and CD34 was 90.5%(0.1%-99.7%),90.1%(1.1%-98.8%)and 81.3%(0.1%-97.8%),respectively.Eighteen cases underwent chromosome examination,of which 5 cases carried with t(9;22)(q34;q11),3 cases with t(v;11q23.3),2 cases with complex karyotypes,and 2 cases with t(9;22)(q34;q11)and complex karyotypes,respectively.Twenty-one cases underwent genetic examination,of which 6 cases were positive for BCR-ABL,3 cases were positive for MLL,1 case was positive for MLL and BCR-ABL,1 case was positive for BCR-ABL and TP53,and 1 case was positive for PHF6 and ASXL1 respectively.Of the 24 patients,7 refused chemotherapy and 17 received induction chemotherapy.Of the patients receiving chemotherapy,9 cases achieved complete remission(CR),1 case was partial remission(PR),and 7 cases were not relieved(NR).In 11 patients treated by ALL-type induction regimen and 6 patients treated by ALL and AML-type induction regimen,8 cases and 1 case achieved CR,the difference in CR rate was statistically significant(P<0.05).In 6 patients with Philadelphia chromosome(Ph)positive and 11 patients with Ph negative,1 case and 8 cases achieved CR,the difference in CR rate was statistically significant(P<0.05).The median follow-up time was 5.5 months(0-36 months).The 3-year overall survival(OS)rate was 17.5%and the median OS time was 6 months.The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation and non-transplanted groups were 75.2%and 0,respectively,and the median OS time was not reached and 4 months(P<0.05).Conclusions MPAL is rare,it mostly co-expresses lymphoid and myeloid antigens and shows a much higher incidence of CD34,CD38 and HLA-DR.MPAL is often associated with Ph positive and complex karyotypes.MPAL has a low remission rate and poor prognosis,and a reasonable and effective treatment plan should be further explored.