Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset.
背景：费城染色体样急性淋巴细胞白血病（Ph样ALL）是B细胞ALL的一种高危亚型，其特征为基因表达谱与BCR::ABL1阳性白血病相似，但缺乏BCR::ABL1融合基因。该亚型常伴随激酶激活变异，如CRLF2重排、JAK-STAT通路突变及ABL类融合基因。Ph样ALL患者在接受常规化疗时通常预后较差，这凸显了强化及靶向治疗策略的必要性。 方法：本综述总结了当前关于造血干细胞移植（HSCT）在Ph样ALL患者中作用的证据。我们分析了回顾性队列研究、注册数据库及正在进行的临床试验，重点关注移植适应症、分子风险分层、可测量残留病（MRD）状态、移植时机及移植后策略。 结果：回顾性数据表明，对于存在高危分子学异常或诱导治疗结束时MRD阳性的患者，在首次完全缓解期（CR1）进行HSCT可能改善生存。然而，缺乏针对Ph样ALL的前瞻性数据限制了明确结论的得出。移植后复发仍是临床挑战，目前正在探索包括使用酪氨酸激酶抑制剂或JAK抑制剂作为移植后维持治疗在内的新型策略。新兴的免疫疗法，如嵌合抗原受体（CAR）T细胞疗法，可能重塑治疗格局并潜在改变移植适应症。 结论：对于特定Ph样ALL患者，尤其是具有不良分子风险特征或持续MRD阳性的患者，HSCT仍是关键治疗选择。然而，仍需进一步前瞻性研究来评估CR1期HSCT的适应症，以及移植与靶向和免疫治疗策略的潜在整合。基于基因组分析和MRD评估的个体化治疗方案对于改善这一高危亚型患者的预后至关重要。
肿瘤(癌症)患者之家