Division of Pediatric Blood Diseases Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Cancer Med. 2021 Feb;10(3):956-964. doi: 10.1002/cam4.3681. Epub 2021 Jan 24.
The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R-AML) remains unclear. The combination of cladribine/Ara-C/granulocyte-colony stimulating factor and mitoxantrone (CLAG-M) shown promising results in adult R/R-AML. We aim to investigate the efficacy and safety of CLAG-M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R-AML children.
Fifty-five R/R-AML children were analyzed. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) at 3-year were documented. Karyotype or mutations status were summarized as different risk groups.
The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one-cycle of CLAG-M and MEC/IEC treatment (p < 0.001). The CLAG-M group's OS (66.8% ± 16.2% vs. 40.4% ± 10.9%, p = 0.019) and PFS (52.6% ± 13.7% vs. 34.9% ± 9.1%, p = 0.036) at 3-year was significantly higher than the MEC/IEC group. In high-risk patients, 33.3% experienced progression of disease (PD) and 22.2% dead in CLAG-M group, while 50% experienced PD and 43.8% dead in MEC/IEC. When it comes to low-risk group, none of them in CLAG-M experienced PD or death, while up to 50% of patients received MEC/IEC suffered PD, and all of them died eventually. Similar results were also found in the intermediate-risk group. Surprisingly, the presence of FLT3-ITD was associated with poor outcome in both groups. The most common adverse events were hematologic toxicities, and the incidence was similar in both group.
CLAG-M group demonstrated effective palliation along with acceptable toxicity in R/R-AML patients. However, patients with FLT3-ITD may benefit less from CLAG-M, owing to higher PD rate and all-cause mortality than other patients.
对于复发/难治性急性髓系白血病（R/R-AML）患儿，首选的挽救治疗方法仍不明确。 cladribine/Ara-C/粒细胞集落刺激因子和米托蒽醌（CLAG-M）联合方案在成人 R/R-AML 中显示出良好的疗效。我们旨在研究 CLAG-M 与米托蒽醌/依托泊苷/阿糖胞苷（MEC）或柔红霉素/依托泊苷/阿糖胞苷（IEC）在 R/R-AML 患儿中的疗效和安全性。
分析了 55 例 R/R-AML 患儿。记录总缓解率（ORR）、总生存期（OS）和 3 年无进展生存期（PFS）。总结核型或突变状态为不同风险组。
1 个周期 CLAG-M 和 MEC/IEC 治疗后，ORR 分别为 80%（16/20）和 51%（18/35）（p<0.001）。CLAG-M 组的 OS（66.8%±16.2% vs. 40.4%±10.9%，p=0.019）和 3 年 PFS（52.6%±13.7% vs. 34.9%±9.1%，p=0.036）明显高于 MEC/IEC 组。在高危患者中，CLAG-M 组有 33.3%发生疾病进展（PD），22.2%死亡，而 MEC/IEC 组有 50%发生 PD，43.8%死亡。在低危组中，CLAG-M 组无 PD 或死亡，而接受 MEC/IEC 治疗的患者中高达 50%发生 PD，且全部死亡。在中危组中也发现了类似的结果。令人惊讶的是，FLT3-ITD 的存在与两组的不良预后相关。最常见的不良反应是血液学毒性，两组的发生率相似。
CLAG-M 组在 R/R-AML 患者中表现出有效的姑息治疗，同时具有可接受的毒性。然而，FLT3-ITD 患者可能从 CLAG-M 中获益较少，因为与其他患者相比，PD 发生率和全因死亡率更高。
