Clinical diagnostics and treatment strategies for Philadelphia chromosome like acute lymphoblastic leukemia
Clinical diagnostics and treatment strategies for Philadelphia chromosome like acute lymphoblastic leukemia
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DOI：
10.1182/bloodadvances.2019000163
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发表时间：
2020-01-14
期刊：
影响因子：
7.5
通讯作者：
Tasian, Sarah K.
中科院分区：
文献类型：
--
作者：
Harvey, Richard C.;Tasian, Sarah K.
费城染色体样b细胞急性淋巴母细胞白血病（ph样ALL）占大龄儿童、青少年和成人b细胞急性淋巴母细胞白血病的15%至30%，并与常规治疗失败率和复发率高相关。目前的临床试验正在评估将酪氨酸激酶抑制剂（TKIs）添加到含有ABL类易位或CRLF2重排以及其他JAK通路改变的ph样ALL的儿童和成人化疗中的疗效。然而，考虑到这种疾病的遗传异质性和ph样all相关改变的细胞遗传学隐匿性，患者的实时诊断可能相当具有挑战性。在这篇综述中，我们讨论了ph样ALL复杂的生物学和临床特征，跨年龄谱，可用的诊断测试方式，以及目前对这些高危患者的临床治疗策略。我们进一步提出了一种实用的、循序渐进的ph样ALL基因检测方法，以促进患者的识别和分配，以进行基于tki的治疗或市售药物的适当临床试验。虽然大多数ph样ALL患者在诱导化疗结束时可以通过目前的临床检测成功识别，但提高诊断效率和敏感性以及减少检测结果的时间将有助于早期治疗干预，并可能改善这些高危患者的临床结果。
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children, adolescents, and adults and is associated with high rates of conventional treatment failure and relapse. Current clinical trials are assessing the efficacy of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy for children and adults with Ph-like ALL harboring ABL class translocations or CRLF2 rearrangements and other JAK pathway alterations. However, realtime diagnosis of patients can be quite challenging given the genetic heterogeneity of this disease and the often cytogenetically cryptic nature of Ph-like ALL-associated alterations. In this review, we discuss the complex biologic and clinical features of Ph-like ALL across the age spectrum, available diagnostic testing modalities, and current clinical treatment strategies for these high-risk patients. We further propose a practical and step-wise approach to Ph-like ALL genetic testing to facilitate the identification and allocation of patients to appropriate clinical trials of TKI-based therapies or commercially available drugs. Although the majority of patients with Ph-like ALL can be successfully identified via current clinical assays by the end of induction chemotherapy, increasing diagnostic efficiency and sensitivity and decreasing time to test resulting will facilitate earlier therapeutic intervention and may improve clinical outcomes for these high-risk patients.