Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Cancer Med. 2020 Jun;9(11):3647-3655. doi: 10.1002/cam4.3023. Epub 2020 Mar 26.
The prognosis of children with acute monocytic leukemia (AML-M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML-M5 children.
We included 132 children with AML-M5. Overall survival (OS) and progression-free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis.
The 5-year-OS was 46.0% (95% confidence intervals, 41.6%-50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P = .009) and hyperleukocytosis (P < .001). The FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) and MLL-rearrangement carriers were associated with fewer survivors in all patients (37.1% and 36.7%) and chemotherapy-only group (19.0% and 35.0%). Notably, the number of survivor with MLL-rearrangement did not increase in hematopoietic stem cell transplant (HSCT) group. According to the Cox regression analysis, HSCT was a significantly favorable factor (P = .001), while hyperleukocytosis, age ≤ 3 years old, and BM blast ≥ 70% adversely affected the OS in all patients (all P < .05). Additionally, FLT3-ITD was a risk factor for OS in the chemotherapy-only group (P = .023), while hyperleukocytosis and age ≤ 3 years independently contributed to poor PFS (both P < .05). In comparison to the standard-risk group, significant poorer outcome was found in the high-risk group (both P < .005).
We propose that AML-M5 children with any of MLL-rearrangement, FLT3-ITD, hyperleukocytosis, BM blast ≥ 70%, or age ≤ 3 years old are classified into the high-risk group, and HSCT is beneficial especially in patients with FLT3-ITD mutation, hyperleukocytosis, and age ≤ 3 years old. Importantly, the choice of HSCT should be made more carefully in children with MLL-rearrangement for its suboptimal performance.
儿童急性单核细胞白血病（AML-M5）的预后仍不理想，风险分层仍存在争议。我们旨在探讨临床和细胞遗传学特征的预后价值，并提出一种新的 AML-M5 儿童风险分层方法。
纳入 132 例 AML-M5 患儿。记录总生存（OS）和无进展生存（PFS）。采用 Cox 回归分析评估预后的潜在危险因素。
所有患者的 5 年 OS 为 46.0%（95%置信区间，41.6%-50.4%）。年龄≤3 岁（P=0.009）和白细胞增多（P<0.001）患者的 OS 显著降低。FLT3 内部串联重复（ITD）和 MLL 重排携带者在所有患者（37.1%和 36.7%）和仅化疗组（19.0%和 35.0%）中幸存者比例较低。值得注意的是，在造血干细胞移植（HSCT）组中，MLL 重排患者的幸存者数量并未增加。根据 Cox 回归分析，HSCT 是一个显著有利的因素（P=0.001），而白细胞增多、年龄≤3 岁和骨髓原始细胞≥70%均对所有患者的 OS 产生不良影响（均 P<0.05）。此外，FLT3-ITD 是仅化疗组 OS 的危险因素（P=0.023），而白细胞增多和年龄≤3 岁独立导致较差的 PFS（均 P<0.05）。与标准风险组相比，高危组的结局明显较差（均 P<0.005）。
我们提出，任何 MLL 重排、FLT3-ITD、白细胞增多、骨髓原始细胞≥70%或年龄≤3 岁的 AML-M5 患儿均归入高危组，HSCT 特别有利于 FLT3-ITD 突变、白细胞增多和年龄≤3 岁的患者。重要的是，由于 MLL 重排患儿的表现不佳，应更谨慎地选择 HSCT。
