急性髓系白血病诱导缓解所需疗程与预后的关系

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探讨急性髓系白血病(AML)患者诱导治疗达完全缓解(CR)所需疗程与预后的关系。

回顾性分析2004年4月至2013年12月收治的397例成人初发AML（急性早幼粒细胞白血病除外）患者的治疗反应、复发和生存情况，初始诱导治疗应用去甲氧柔红霉素联合阿糖胞苷(IA“3+7”)方案，CR后给予巩固化疗，有移植条件的患者在第1次缓解期行异基因造血干细胞移植(allo-HSCT)。

在397例患者中可评估的CR患者为347例，存活的CR患者中位随访时间18.0(2.4~115.4)个月，CR患者3年累积复发率(CIR)、无病生存(DFS)率和总生存(OS)率分别为33.0%、58.6%和67.1%。多因素分析显示：细胞遗传学危险度高、达CR所需疗程数多、未行allo-HSCT是影响DFS和OS的共同危险因素，FLT3-ITD突变阳性是影响DFS的独立危险因素。1个疗程达CR（255例）和2个疗程达CR（73例）的患者之间DFS和OS率差异均无统计学意义（P>0.05），而两组患者的DFS（P值分别为0.002和0.030）和OS率（P值分别为0.006和0.061）均优于≥3个疗程达CR组（19例）。在183例持续化疗患者中，多因素分析显示：2个疗程内达CR是改善DFS和OS的共同独立预后因素（P值分别为0.001和0.035）。

IA方案初始诱导治疗AML，2个疗程内获得CR有利于改善CR患者的DFS和OS。

To explore the relationship between induction chemotherapy cycles to achieve complete remission (CR) and prognosis in patients with acute myeloid leukemia (AML).

From April 2004 to December 2013, 397 adult patients with newly diagnosed AML (acute promyelocytic leukemia excluded) received the idarubicin combined with cytarabine (IA) “3+ 7” regimen as the first induction chemotherapy were enrolled in the study. Therapeutic effect, relapse and survival of these patients were discussed. Patients underwent continuous consolidation chemotherapy, and some eligible patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first complete remission.

Of 397 patients, 347 evaluable patients achieved CR after 1–4 cycles induction chemotherapy. The median follow-up was 18.0 (2.4–115.4) months in survivors, the cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) at 3 years were 33.0%, 58.6% and 67.1%, respectively. Multivariate analysis revealed that unfavorable cytogenetics, more cycles to achieve CR and post-remission treatment without allo-HSCT were independent risk factors affecting DFS and OS. FLT3-ITD mutation positive was another independent risk factor affecting DFS. There was no statistic difference between patients who achieved CR after one cycle (n=255) and two cycles (n=73) treatment in DFS and OS (P>0.05). DFS and OS in patients who achieved CR after 3 or 4 cycles (n=19) were significantly lower than the above two groups (P影响急性髓系白血病CR患者DFS和OS的多因素分析结果因素DFSOS相对危险度95%CIP值相对危险度95%CIP值细胞遗传学预后（良好/中等/不良）1.5211.054～2.1950.0251.8191.161～2.8500.009达CR所需疗程数（1个疗程/2个疗程/≥ 3个疗程）1.6031.147～2.2400.0061.5931.083～2.3450.018缓解后治疗模式（化疗/allo-HSCT）0.3340.222～0.5041、2、≥3个疗程达完全缓解(CR)3组急性髓系白血病患者发病时疾病特征比较项目1个疗程达CR（255例）2个疗程达CR（73例）≥3个疗程达CR（19例）P值性别［例（%）］0.221 男126（49.4）43（58.9）12（63.2） 女129（50.6）30（41.1）7（36.8）年龄 M（范围）（岁）38（18～62）34（18～59）39（18～61）0.741 达完全缓解(CR)所需不同疗程数患者无病生存(A)和总生存(B)的比较

4．持续化疗患者的复发和生存：在持续化疗的183例CR患者中，复发78例，死亡54例，其中47例死于复发，非复发死亡7例。3年CIR、DFS率、OS率分别为(58.9±5.0)%、（38.2±4.9）%和(50.9± 5.5)%。2个疗程内达CR（170例）与≥3个疗程CR（13例）存活患者中位随访时间分别为12和14个月，中位复发时间分别为5.9和2.9个月（P=0.001），中位DFS时间分别为17.9和3.3个月（P=0.004），中位OS时间分别为39.6和16.1个月（P=0.029）。多因素分析显示：2个疗程内达CR（HR 0.259, 95%CI 0.116~0.575,P=0.001)、FLT3-ITD基因突变阴性（HR 0.377, 95%CI 0.221~0.645,P 0.05)；预后中等组2个疗程内达CR患者2年DFS率和OS率均高于≥3个疗程CR患者（P值分别持续化疗患者中2个疗程内达完全缓解（CR组）与≥3个疗程达CR组生存的比较组别例数2年DFS率（%）2年OS率（%）预后良好组 2个疗程内达CR4850.8±8.971.9±8.3 ≥3个疗程达CR644.4±22.260.0±21.9预后中等组 2个疗程内达CR9442.5±6.866.8±6.5 ≥3个疗程达CR728.6±17.1a35.7±19.8bFLT3突变阴性 2个疗程内达CR14150.7±6.366.8±5.2 ≥3个疗程达CR833.3±18.0b30.0±23.1bNPM1突变阴性 2个疗程内达CR13443.2±5.562.4±5.7 ≥3个疗程达CR1237.5±15.3b47.6±17.7IDA初始剂量10 mg/m2 2个疗程内达CR10449.7±6.769.1±7.0 ≥3个疗程达CR616.7±15.2a50.0±20.4bIDA初始剂量8 mg/m2 2个疗程内达CR6640.3±6.655.3±6.9 ≥3个疗程达CR743.6±20.144.4±22.2Open in a separate window

注：DFS：无病生存；OS：总生存；IDA：去甲氧柔红霉素；与2个疗程内达CR组比较，aP