Gong X Y, Wang Y, Liu B C, Wei H, Li C W, Li Q H, Zhao J W, Zhou C L, Lin D, Liu K Q, Wei S N, Gong B F, Zhang G J, Liu Y T, Zhao X L, Li Y, Gu R X, Qiu S W, Mi Y C, Wang J X
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2018 Jan 14;39(1):9-14. doi: 10.3760/cma.j.issn.0253-2727.2018.01.003.
To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (=0.688). Multivariate analysis revealed that high WBC (=1.825, 95% 1.022-3.259, =0.042), one cycle to achieve CR (=0.130, 95% 0.063-0.267, <0.001), post-remission treatment with allo-HSCT (=0.169, 95% 0.079-0.362, <0.001) were independent prognostic factors affecting OS. AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.
分析成人急性髓系白血病(AML)伴MLL基因重排患者的临床、实验室特征及预后。回顾性分析2010年1月至2016年12月92例成人AML伴MLL基因重排患者的病历资料。在1417例成人AML(非M3型)患者中,共识别出92例(6.5%)伴MLL基因重排,患者年龄中位数为35.5岁(15至64岁),男女比例均等,白细胞计数中位数为21.00(0.42 - 404.76)×10⁹/L,根据FAB分类,78例(84.8%)为急性单核细胞白血病。在32例患者中检测到11种常见伙伴基因,9例(28.1%)为MLL/AF9(+),5例(15.6%)为MLL/AF6(+),5例(15.6%)为MLL/ELL(+),2例(6.3%)为MLL/AF10(+),1例(3.1%)为MLL/SETP6(+),其余10例患者的伙伴基因未被识别。92例患者中,83例纳入预后分析,中位随访时间为10.3(0.3 - 74.0)个月,完全缓解(CR)率为85.5%(71/83),中位总生存期(OS)和无复发生存期(RFS)分别为15.4个月和13.1个月。两年OS率和RFS率分别为36.6%和29.5%。31例接受异基因造血干细胞移植(allo - HSCT)的患者中,接受和未接受allo - HSCT患者的两年OS率和RFS率分别为57.9%和21.4%、52.7%和14.9%(P < 0.001)。在检测伙伴基因的患者中,32例中有9例(28.1%)为MLL/AF9(+),中位随访时间为6.0(4.1 - 20.7)个月。3例MLL/AF9患者接受了allo - HSCT。23例(71.9%)为非MLL/AF9(+),中位随访时间为7.8(0.3 - 26.6)个月。14例(60.1%)非MLL/AF9患者接受了allo - HSCT。MLL/AF9和非MLL/AF9患者的一年OS率分别为38.1%和55.5%(P = 0.688)。多因素分析显示,高白细胞计数(P = 0.042,95%CI 1.022 - 3.259)、达到CR需1个周期(P < 0.001,95%CI 0.063 - 0.267)、缓解后接受allo - HSCT治疗(P < 0.001,95%CI 0.079 - 0.362)是影响OS的独立预后因素。AML伴MLL基因重排与单核细胞分化密切相关,MLL/AF9是最常见的伙伴基因。传统化疗缓解率高,但易复发,allo - HSCT可能有进一步改善该组患者预后的潜力。