Carobolante Francesca, Chiaretti Sabina, Skert Cristina, Bassan Renato
UOC Ematologia, Ospedale dell'Angelo, Venezia, Mestre, Italy.
Division of Hematology, 'Sapienza' University, Rome, Italy.
Ther Adv Hematol. 2020 Feb 3;11:2040620720903531. doi: 10.1177/2040620720903531. eCollection 2020.
The outstanding therapeutic progress achieved with modern pediatric regimens in childhood acute lymphoblastic leukemia (ALL) led efforts to explore whether a similar treatment approach could be equally effective and safe in older patients, starting initially with older adolescents and young adults (AYA), variably defined in different studies by an age between 15-18 and 25-39 years. Several comparative and noncomparative trials of this type have been carried out during the last two decades, enrolling thousands of patients. Almost without exception, the new strategy improved patients' outcomes compared with traditional adult treatments in B-lineage and T-lineage Philadelphia (Ph) chromosome-negative B-ALL, while the use of tyrosine kinase inhibitors (TKI) led to comparative progress in Ph+ ALL, a former high-risk subset more typically observed in older age groups. At present, highly effective pediatric-based regimens warrant 5-year survival rates of 60-70% in AYA patients. In view of these data, the same approach was progressively extended to older patients, improving the results up to 55 years of age. Issues of treatment compliance and drug-related toxicity have thus far prevented a comparable therapeutic advancement in patients aged >55 years. This critical review updates and summarizes with pertinent examples this global, positive therapeutic change, and examines how to promote further progress with new targeted therapies that include novel immuno-therapeutics and other agents developed against the many molecular dysfunctions detectable in various ALL subsets. Substantial progress is expected to occur soon, bringing AYA survival figures very close to that of children, and also to improve the outcome of ALL at all ages.
现代儿科方案在儿童急性淋巴细胞白血病（ALL）治疗方面取得的显著进展，促使人们探索类似的治疗方法在年龄较大的患者中是否同样有效和安全，最初是从年龄较大的青少年和青年成人（AYA）开始，在不同研究中对其年龄范围的定义有所不同，为15至18岁以及25至39岁之间。在过去二十年中开展了几项此类比较性和非比较性试验，纳入了数千名患者。几乎毫无例外，与传统成人治疗相比，新策略改善了B系和T系费城（Ph）染色体阴性B-ALL患者的预后，而酪氨酸激酶抑制剂（TKI）的使用在Ph+ ALL中带来了相当的进展，Ph+ ALL是一个以前在年龄较大的人群中更常见的高风险亚组。目前，基于儿科的高效方案使AYA患者的5年生存率达到60%至70%。鉴于这些数据，相同的方法逐渐扩展到年龄更大的患者，将结果改善至55岁。迄今为止，治疗依从性和药物相关毒性问题阻碍了年龄>55岁患者取得类似的治疗进展。这篇批判性综述用相关实例更新并总结了这一全球性的积极治疗变革，并探讨如何通过新的靶向治疗促进进一步进展，这些新的靶向治疗包括新型免疫治疗和针对各种ALL亚组中可检测到的多种分子功能障碍开发的其他药物。预计很快会取得实质性进展，使AYA的生存率非常接近儿童，并改善所有年龄段ALL的预后。
