We sought to appraise the value of overall response and salvage chemotherapy, inclusive of allogeneic hematopoietic stem cell transplant (AHSCT), in primary refractory acute myeloid leukemia (prAML). For establishing consistency in clinical practice, the 2017 European LeukemiaNet (ELN) defines prAML as failure to attain CR after at least 2 courses of intensive induction chemotherapy. Among 60 consecutive patients (median age 63 years) correspondent with ELN-criteria for prAML, salvage was documented in 48 cases, 30/48 (63%) being administered intensive chemotherapy regimens and 2/48 consolidated with AHSCT as first line salvage. 13/48 (27%) attained response: CR, 7/13 (54%), CRi, 2/13 (15%), MLFS, 4/13 (31%). The CR/CRi rate was 9/48 (19%), with CR rate of 7/48 (15%). On univariate analysis, intermediate-risk karyotype was the only predictor of response (44% vs 17% in unfavorable karyotype; P = 0.04). Administration of any higher-dose (>1 g/m2) cytarabine intensive induction (P = 0.50), intensive salvage chemotherapy (P = 0.72), targeted salvage (FLT3 or IDH inhibitors) (P = 0.42), greater than 1 salvage regimen (P = 0.89), age < 60 years (P = 0.30), and de novo AML (P = 0.10) did not enhance response achievement, nor a survival advantage. AHSCT was performed in 12 patients with (n = 8) or without (n = 4) CR/CRi/MLFS. 1/2/5-year overall survival (OS) rates were 63%/38%/33% in patients who received AHSCT (n = 12) vs 27%/0%/0% in those who achieved CR/CRi/MLFS but were not transplanted (n = 5), vs 14%/0%/0% who were neither transplanted nor achieved CR/CRi/MLFS (n = 43; P < 0.001); the median OS was 18.6, 12.6 and 5.6 months, respectively. Although CR/CRi/MLFS bridged to AHSCT (n = 8), appeared to manifest a longer median OS (20 months), vs (13.4 months) for those with no response consolidated with AHSCT (n = 4), the difference was not significant P = 0.47. We conclude AHSCT as indispensable for securing long-term survival in prAML (p = 0.03 on multivariate analysis), irrespective of response achievement.
本研究旨在评估总体缓解情况及挽救性化疗（包括异基因造血干细胞移植[AHSCT]）对原发性难治性急性髓系白血病（prAML）的治疗价值。为统一临床实践标准，2017版欧洲白血病网（ELN）将prAML定义为至少接受2个疗程强化诱导化疗后仍未能达到完全缓解（CR）的疾病。在连续纳入的60例符合ELN标准的prAML患者（中位年龄63岁）中，48例接受了挽救治疗，其中30/48例（63%）采用强化化疗方案，2/48例将AHSCT作为一线挽救治疗方案。13/48例（27%）获得缓解：CR 7/13例（54%）、CRi 2/13例（15%）、MLFS 4/13例（31%）。CR/CRi率为9/48（19%），其中CR率为7/48（15%）。单变量分析显示，中危核型是唯一能预测治疗反应的指标（缓解率44% vs 不良核型17%；P=0.04）。而使用任何高剂量（>1 g/m²）阿糖胞苷强化诱导（P=0.50）、强化挽救化疗（P=0.72）、靶向挽救治疗（FLT3或IDH抑制剂）（P=0.42）、使用超过1种挽救方案（P=0.89）、年龄<60岁（P=0.30）以及原发初治AML（P=0.10）均未能提高缓解率或改善生存获益。共12例患者接受了AHSCT，其中8例达到CR/CRi/MLFS，4例未达到缓解。接受AHSCT的患者（n=12）1/2/5年总生存（OS）率分别为63%/38%/33%，达到CR/CRi/MLFS但未移植者（n=5）为27%/0%/0%，既未移植也未达到CR/CRi/MLFS者（n=43）为14%/0%/0%（P<0.001）；中位OS分别为18.6、12.6和5.6个月。虽然通过AHSCT实现CR/CRi/MLFS桥接治疗的患者（n=8）中位OS（20个月）较无缓解但接受AHSCT巩固治疗者（n=4，13.4个月）更长，但差异无统计学意义（P=0.47）。我们结论认为，无论是否达到缓解，AHSCT对确保prAML患者长期生存均不可或缺（多变量分析p=0.03）。
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