Starý Jan, Hrušák Ondřej
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
F1000Res. 2016 Nov 4;5:2635. doi: 10.12688/f1000research.9548.1. eCollection 2016.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Despite enormous improvement of prognosis during the last half century, ALL remains a major cause of childhood cancer-related mortality. During the past decade, whole genomic methods have enhanced our knowledge of disease biology. Stratification of therapy according to early treatment response measured by minimal residual disease allows risk group assignment into different treatment arms, ranging from reduction to intensification of treatment. Progress has been achieved in academic clinical trials by optimization of combined chemotherapy, which continues to be the mainstay of contemporary treatment. The availability of suitable volunteer main histocompatibility antigen-matched unrelated donors has increased the rates of hematopoietic stem cell transplantation (HSCT) over the past two decades. Allogeneic HSCT has become an alternative treatment for selected, very-high-risk patients. However, intensive treatment burdens children with severe acute toxic effects that can cause permanent organ damage and even toxic death. Immunotherapeutic approaches have recently come to the forefront in ALL therapy. Monoclonal antibodies blinatumomab and inotuzumab ozogamicin as well as gene-modified T cells directed to specific target antigens have shown efficacy against resistant/relapsed leukemia in phase I/II studies. Integration of these newer modalities into combined regimens with chemotherapy may rescue a subset of children not curable by contemporary therapy. Another major challenge will be to incorporate less toxic regimens into the therapy of patients with low-risk disease who have a nearly 100% chance of being cured, and the ultimate goal is to improve their quality of life while maintaining a high cure rate.
急性淋巴细胞白血病（ALL）是儿童期最常见的恶性肿瘤。尽管在过去半个世纪里预后有了巨大改善，但ALL仍然是儿童癌症相关死亡的主要原因。在过去十年中，全基因组方法增进了我们对疾病生物学的了解。根据微小残留病测量的早期治疗反应对治疗进行分层，可将风险组分配到不同的治疗方案中，从减少治疗到强化治疗。通过优化联合化疗，学术临床试验已取得进展，联合化疗仍是当代治疗的主要手段。在过去二十年中，合适的志愿主要组织相容性抗原匹配的无关供体的可获得性提高了造血干细胞移植（HSCT）的比例。异基因HSCT已成为选定的极高风险患者的替代治疗方法。然而，强化治疗给儿童带来了严重的急性毒性作用，可导致永久性器官损伤甚至中毒死亡。免疫治疗方法最近在ALL治疗中占据了前沿位置。单克隆抗体贝林妥欧单抗和奥英妥珠单抗以及针对特定靶抗原的基因修饰T细胞在I/II期研究中已显示出对耐药/复发白血病的疗效。将这些较新的治疗方式与化疗联合方案相结合，可能挽救一部分当代治疗无法治愈的儿童患者。另一个主要挑战将是把毒性较小的方案纳入低风险疾病患者的治疗中，这些患者几乎有100%的治愈机会，最终目标是在保持高治愈率的同时提高他们的生活质量。
