Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Sydney, New South Wales, Australia.
Genes Chromosomes Cancer. 2024 Sep;63(9):e23269. doi: 10.1002/gcc.23269.
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is a high risk form of ALL associated with dismal outcomes in the pre-tyrosine kinase inhibitor (TKI) era. Addition of a TKI to chemotherapy improves outcomes. Therefore, testing for the presence of the Philadelphia chromosome by at least two methods at the time of diagnosis is critical. Diagnostic testing may include karyotype, fluorescent in situ hybridisation (FISH), and RT-PCR for the BCR::ABL1 transcript. The significance of low-level BCR::ABL1 transcript by RT-PCR in the absence of the Philadelphia chromosome on karyotype or by FISH is unknown.
This is a retrospective review of children diagnosed with acute leukemia at our institution from 2010 to 2020. Those positive for the BCR::ABL1 transcript by qualitative RT-PCR, and negative for t(9;22) by karyotype or FISH were analyzed for demographics, cytogenetic and molecular features at diagnosis and relapse, treatment and outcomes. The Kaplan-Meier method was used to estimate event-free and overall survival.
Forty-seven of 306 (15%) patients with Ph- ALL had low-level BCR::ABL1 detected by RT-PCR. Most (77%) had B-cell ALL. The e1a2 transcript was detected most frequently, in 43 (91%) patients. BCR::ABL1 was quantifiable in 12/43 (28%) patients, with a median of 0.0008% (range 0.0003-0.095%). Seven patients (15%) relapsed. No patient with low-level BCR::ABL1 at diagnosis developed Ph + ALL at relapse. There was no difference in 5-year event-free (77% versus 81%, p = 0.407) or overall survival (86% versus 91%, p = 0.3) between children with low-level BCR::ABL1 (n = 47) and those without (n = 259).
BCR::ABL1 low-level positivity in children with newly diagnosed Ph- ALL is a relatively common finding and did not adversely affect outcome for patients treated using a contemporary risk-adapted approach.
费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）是一种高风险形式的 ALL，在酪氨酸激酶抑制剂（TKI）时代之前与预后不良相关。在化疗中加入 TKI 可改善预后。因此，在诊断时至少使用两种方法检测费城染色体的存在至关重要。诊断检测可能包括核型、荧光原位杂交（FISH）和 BCR::ABL1 转录本的实时聚合酶链反应（RT-PCR）。在核型或 FISH 无费城染色体的情况下，通过 RT-PCR 检测到低水平的 BCR::ABL1 转录本的意义尚不清楚。
这是对 2010 年至 2020 年在我们机构诊断为急性白血病的儿童进行的回顾性研究。通过定性 RT-PCR 检测到 BCR::ABL1 转录本阳性，且核型或 FISH 检测不到 t(9;22)的患者，分析其诊断时和复发时的人口统计学、细胞遗传学和分子特征、治疗和结果。采用 Kaplan-Meier 法估计无事件生存率和总生存率。
306 例 Ph-ALL 患者中有 47 例（15%）通过 RT-PCR 检测到低水平的 BCR::ABL1。大多数（77%）为 B 细胞 ALL。在 43 例（91%）患者中检测到最常见的 e1a2 转录本。在 12/43（28%）例患者中可定量检测到 BCR::ABL1，中位数为 0.0008%（范围 0.0003-0.095%）。7 例患者（15%）复发。在诊断时存在低水平 BCR::ABL1 的患者中，无一例在复发时发展为 Ph+ALL。低水平 BCR::ABL1 组（n=47）与无低水平 BCR::ABL1 组（n=259）的 5 年无事件生存率（77%对 81%，p=0.407）和总生存率（86%对 91%，p=0.3）无差异。
在新诊断的 Ph-ALL 患儿中，BCR::ABL1 低水平阳性是一种较为常见的发现，采用现代风险适应治疗方法治疗的患者，其结局未受不利影响。
