34例同时伴FLT3-ITD突变及MLL基因异常的急性髓系白血病患者的临床特征及转归

Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tan- dem duplication and MLL gene rearrangement

目的探讨同时伴FLT3-ITD突变及MLL基因异常的急性髓系白血病（AML）患者的临床特征及转归。方法回顾性分析34例同时伴FLT3-ITD突变及MLL基因异常的AML患者的临床资料，比较化疗、化疗加靶向药物治疗及allo—HSCT的疗效及影响因素。结果34例同时伴FLT3-ITD突变及MLL基因异常的AML患者占同期住院AML患者的2．02％。入院时WBC〉30×109／L的患者占63．6％，其中WBC〉50×109／L者占39．4％。FAB亚型中以M，比例最高，占3513％，染色体核型异常者达63．6％，其中复杂异常占12．1％。34例患者中仅有FLT3-ITD及MLL基因异常（双基因异常）者11例（32．4％），具FLT3及MLL以外的1种及1种以上的基因异常（多基因异常）者23例（67．6％）。34例患者2个疗程完全缓解（CR）率为29．4％，7例（20．6％）化疗≥3个疗程后CR，CR患者的早期复发率为52．9％。WBC〉50×109／L以及多基因异常的患者2个疗程CR率较低（7．7％、5．4％），其中具有3种以上基因异常的患者无一例CR。34例患者2年总生存（OS）率为28．8％（95％CI 13．5％～46．0％），2年无病生存（DFS）率为27．1％（95％CI 12．5％～44．0％）。18例仅使用化疗或化疗加靶向药物治疗的患者，17例在2年内死亡，1例放弃治疗后失访。接受allo—HSCT治疗的患者3年OS率为43．4％（95％CI 13．7％～70．4％），3年DFS率为42．7％（95％CI 13．4％～69．7％）。结论同时伴FLT3-ITD突变及MLL基因异常的AML患者FAB分型以M5多见，常伴高白细胞血症、细胞遗传学异常及多基因异常。患者化疗缓解率低，早期复发率高，长期生存率低。高白细胞血症、多基因异常可能是此类患者疗效差的重要原因，allo-HSCT可改善患者的转归。

Objective To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia （AML） with FLT3 internal tandem duplication （FLT3-ITD） and MLL gene rearrangement. Methods The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stern cell transplantation （allo-HSCT）. Results Of the thirty-four cases with median age 41 （4-71） years old, 63.6% presented with white blood cells （WBC） greater than 30×109/L, 39.4% greater than 50 × 109/L respectively on admission. M5 （35.3%） made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients （32.35%） had both FLT3- ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients （67.6%） had one or more other gene abnormalities （multiple gene abnormalities）. Of the 34 cases, 29.4% patients went into complete remission （CR） after two courses of chemotherapy. 20.6% （7 patients） went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC 〉 50 × 109/L or multiple gene abnormalities had a lower remission rate （7.7%, 5.4%） after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival （OS） in the 34 patients was 28.8% （95% CI 13.5%-46.0%） and the disease-free survival （DFS） was 27.1% （95% CI 12.5%-44.0% ）. Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% （95% CI 13.7%- 70.4%） and DFS 42.7% （95% CI 13.4%-69.7%）. Conclusion AML patients with FLT3-ITD and MLL gene rearrangement often presented with Ms, accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.