Abstract：
Philadelphia chromosome positive (Ph+) acute lymphoblastic lymphoma (ALL) is an uncommon subtype of ALL in children, seen in 2-5% cases. Diagnostic evaluation includes conventional karyotyping and detection of BCR-ABL1 translocation by fluorescence in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR). For children, the frontline management includes combination of intensive chemotherapy along with imatinib (300-340 mg/m2/d) or dasatinib (60-80 mg/m2/d). Imatinib/dasatinib should be introduced in induction as soon as results for BCR-ABL are available. Minimal residual disease (MRD) monitoring is essential; multi-parametric flowcytometry and immunoglobulin/T-cell receptor rearrangement PCR are the preferred methods. Intrathecal therapy with at least 12 doses of methotrexate is adequate for central nervous system (CNS) prophylaxis, but cranial radiation is necessary for CNS3 involvement. Allogeneic hematopoietic stem cell transplantation (HSCT) in first remission may be considered in high-risk cases (persistent MRD positivity/induction failure). Maintenance therapy with tyrosine kinase inhibitors (TKI) in children is debatable, with potential concerns for long term adverse effects. At relapse, the choice of TKI is guided by the presence of BCR-ABL tyrosine kinase domain resistance mutations, although the frequency of resistance mutations in children are lower. Allogeneic HSCT is essential for consolidation in second remission, if not done. Ph-like ALL is a newly recognized molecular entity, with gene expression profile similar to Ph+ALL and poor survival outcomes. In resource-constrained settings, a stepwise cost-effective diagnostic evaluation should be considered among high-risk patients without recurrent genetic abnormalities. Current treatment strategies remain similar to Ph-negative ALL. Enrolment in clinical trials is encouraged for such children to evaluate potential targeted agents in this subtype.
摘要：
费城染色体阳性（Ph+）急性淋巴母细胞淋巴瘤（ALL）是儿童中罕见的ALL亚型，见于2-5%的病例。诊断评估包括常规核型分析和通过荧光原位杂交（FISH）或逆转录酶聚合酶链反应（RT-PCR）检测BCR-ABL1易位。对于孩子们来说,一线管理包括强化化疗联合伊马替尼(300-340mg/m2/d)或达沙替尼(60-80mg/m2/d).一旦获得BCR-ABL的结果，就应将伊马替尼/达沙替尼引入诱导。微小残留病（MRD）监测是必不可少的；多参数流式细胞术和免疫球蛋白/T细胞受体重排PCR是首选方法。鞘内治疗至少12剂甲氨蝶呤足以预防中枢神经系统（CNS），但CNS3受累需要头颅放射.首次缓解的异基因造血干细胞移植（HSCT）可在高危病例（持续MRD阳性/诱导失败）中考虑。酪氨酸激酶抑制剂（TKI）在儿童中的维持治疗是有争议的，对长期不利影响的潜在担忧。在复发时，TKI的选择以BCR-ABL酪氨酸激酶结构域抗性突变的存在为指导，尽管儿童耐药突变的频率较低。同种异体HSCT对于第二次缓解的巩固至关重要，如果没有完成。Ph-likeALL是一种新认识的分子实体，基因表达谱与Ph+ALL相似，生存结果较差。在资源受限的设置中，在没有复发遗传异常的高危患者中,应考虑逐步进行具有成本效益的诊断评估.目前的治疗策略仍然与Ph阴性ALL相似。鼓励此类儿童参加临床试验，以评估该亚型中潜在的靶向药物。
