Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities. Currently, it is advisable to use less intensive induction regimens for Ph+ ALL. These regimens can achieve high rates of complete remission while causing fewer induction deaths. For consolidation therapy, chemotherapy should remain relatively intensive, with careful monitoring of the BCR-ABL1 molecular transcript and minimal residual disease. AlloSCT may be considered, especially for patients who do not achieve complete molecular remission or have high-risk genetic abnormalities, such as IKZF1-plus. If there is a loss of molecular response, it is essential to screen patients for ABL mutations and, ideally, change the TKI therapy. The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.
近期研究表明，超过半数新诊断的费城染色体阳性急性淋巴细胞白血病成年患者现可获得治愈。然而，在资源有限的环境中确定最合适的治疗方案仍具挑战性。在此类情况下，我们必须考虑治疗毒性风险、新型药物可及性不足以及异基因造血干细胞移植设施受限等问题。目前建议对费城染色体阳性急性淋巴细胞白血病采用较低强度的诱导方案，这类方案能在减少诱导期死亡的同时实现较高的完全缓解率。巩固治疗阶段应维持相对强化的化疗方案，并密切监测BCR-ABL1分子转录本及微小残留病。对于未达到完全分子学缓解或携带高危遗传异常（如IKZF1-plus）的患者，可考虑异基因造血干细胞移植。若出现分子学反应丢失，必须进行ABL突变筛查，并尽可能更换酪氨酸激酶抑制剂治疗方案。其中T315I突变是最常见的耐药机制，可针对性使用普纳替尼进行治疗。双特异性抗体药物贝林妥欧单抗与酪氨酸激酶抑制剂在该疾病治疗中展现出显著协同作用，除在一线治疗中取得卓越疗效外，亦是理想的挽救治疗方案。
How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings
肿瘤(癌症)患者之家