Aldoss Ibrahim, Advani Anjali S
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
Department of Leukemia, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
Best Pract Res Clin Haematol. 2021 Mar;34(1):101242. doi: 10.1016/j.beha.2021.101242. Epub 2021 Jan 11.
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subset of B-cell ALL characterized by high rates of treatment failure. Unsatisfactory outcomes with frontline therapy in adults with Ph-like ALL have been observed irrespective of the employed regimen, including modern pediatric-inspired regimens. Notably, Ph-like ALL is not an uncommon entity in adults, and it's prevalence extends to older patients with B-cell ALL. As the majority of Ph-like ALL cases harbor genetic alterations in kinases and/or cytokine receptors, the integration of tyrosine kinase inhibitors in newly diagnosed patients and poor early responders with Ph-like ALL has emerged as an area of active research with several ongoing clinical trials. Furthermore, the encouraging activity of novel therapies such as inotuzumab and blinatumomab in chemo-refractory B-cell ALL has promoted an interest in introducing these agents early in Ph-like ALL management, which may lead to improved cure rates with frontline therapies, sparing more adults from undergoing early allogeneic hematopoietic cell transplantation (HCT). Finally, the high relapse rate in patients with Ph-like ALL, does not necessary correlate with early minimal residual disease (MRD) response, raising the question of consolidation with allogenic HCT in all adults with Ph-like ALL in first complete remission irrespective of MRD response.
费城样(Ph样)急性淋巴细胞白血病(ALL)是B细胞ALL的一个高危亚组,其特征是治疗失败率高。无论采用何种治疗方案,包括现代儿科启发的方案,在成人Ph样ALL患者中,一线治疗的效果都不尽人意。值得注意的是,Ph样ALL在成人中并非罕见实体,其患病率延伸至老年B细胞ALL患者。由于大多数Ph样ALL病例存在激酶和/或细胞因子受体的基因改变,在新诊断患者和Ph样ALL早期反应不佳者中整合酪氨酸激酶抑制剂已成为一个活跃的研究领域,有多项正在进行的临床试验。此外,诸如伊尼妥单抗和博纳吐单抗等新型疗法在化疗难治性B细胞ALL中的令人鼓舞的活性,促使人们有兴趣在Ph样ALL治疗早期引入这些药物,这可能会提高一线治疗的治愈率,使更多成人不必过早接受异基因造血细胞移植(HCT)。最后,Ph样ALL患者的高复发率与早期微小残留病(MRD)反应不一定相关,这就提出了一个问题,即对于所有首次完全缓解的成人Ph样ALL患者,无论MRD反应如何,是否都需要进行异基因HCT巩固治疗。