Department of Pediatric Hematology, Caihong Hospital of Xianyang, Xi'an, People's Republic of China.
Department of Hematology, Chengdu Women and Children's Central Hospital, Chengdu, People's Republic of China.
BMC Cancer. 2022 Aug 6;22(1):859. doi: 10.1186/s12885-022-09804-w.
The KMT2A gene, formerly named the MLL gene, is rearranged (KMT2Ar) in 70-75% of infants, 5-6% of children and 10-15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations.
A total of 48 B-ALL children with KMT2Ar were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy.
The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 × 10/L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group (P < 0.05). 11q23 was detected in 18 patients; KMT2Ar was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT-PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2Ar were identified. KMT2A-AFF1, KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate (P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 ± 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 ± 8.48% or 40.84 ± 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 × 10/L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2Ar (P < 0.05).
KMT2A 基因（以前称为 MLL 基因）在 70-75%的婴儿、5-6%的儿童和 10-15%的成年 B 细胞急性淋巴细胞白血病（B-ALL）患者中发生重排（KMT2Ar）。儿科病例化疗后的预后仍然较差，只有少数研究调查了中国人群的临床和实验室特征、治疗反应和预后。
共纳入 48 例 KMT2Ar B-ALL 患儿，按年龄分组收集和分析临床和实验室数据。对接受化疗的这些患者进行了预后与传统危险因素和治疗反应的关系研究。
纳入的 48 例患者包括 28 例男性和 20 例女性；18 例（37.50%）或 30 例（62.50%）患者年龄小于 12 个月（婴儿 B-ALL）或发病时年龄大于 12 个月。7 例（14.58%）患者初始白细胞计数为 300×10/L；5 例（10.41%）或 3 例（6.25%）患者分别出现睾丸白血病（TL）或中枢神经系统受累。年龄组在性别或初始白细胞计数方面无统计学差异，而婴儿组 TL 更为常见（P<0.05）。18 例患者检测到 11q23；FISH 或多重 RT-PCR 技术分别检测到 46 例（95.83%）或 45 例（93.75%）患者 KMT2Ar；18 例患者获得 RNA-seq 数据，鉴定出 3 例罕见的 KMT2Ar。KMT2A-AFF1、KMT2A-MLLT3 和 KMT2A-MLLT1 是最常见的转录本。年龄组之间在地塞米松诱导、骨髓（BM）涂片状态和不同时间点（TP）的微小残留病（MRD）水平、治疗相关死亡率（TRM）或完全缓解（CR）率方面无治疗反应差异（P>0.05）；同一 TP 监测的 FCM 或 PCR 的 MRD 水平不等。4 例患者因治疗死亡，TRM 为 8.33%；40 例患者获得 CR，队列的 CR 率为 83.33%。7 例患者退出，15 例患者复发，5 年累积复发率为 59.16±9.16%；包括和排除 TRM 组的患者 5 年前瞻性无事件生存（pEFS）分别为 36.86±8.48%或 40.84±9.16%。对无 TRM 的 37 例患者进行预后和风险比的多变量分析，结果表明初始白细胞计数>300×10/L 和 FCM-MRD 阳性水平与 KMT2Ar 阳性 B-ALL 患者的不良预后密切相关（P<0.05）。
