Thomas Angela
Royal Hospital for Sick Children, Edinburgh, UK.
Hematology Am Soc Hematol Educ Program. 2015;2015:414-9. doi: 10.1182/asheducation-2015.1.414.
The past 70 years have seen childhood acute lymphoblastic leukemia move from a fatal disease with a survival of barely 4 months to a curable disease in >85% of patients. It has become clear that as treatment has intensified, more children are cured but at the expense of increased toxicity which for some can cause significant long-term morbidity and even mortality. The drive in more recent years has been to identify sensitive markers of disease and response to treatment to allow a reduction in therapy in those who do not require it and more intensive treatment in those who do. Clinical characteristics have been used to stratify patients into different risk groups and this, coupled with following response at a molecular level, has done much to tailor treatment to the patient. Considerable research has been focused on the molecular characteristics of the leukemia itself to elucidate the biologic mechanisms underlying both the disease and the comparative or absolute resistance of some types of leukemia. These molecular markers can also act as targets for novel therapies, which require newer trial methodologies to prove their utility. There has been less focus on the biology of the patient but it is clear that some patients are more susceptible to adverse events and toxicities than others. Through the use of pharmacogenomics, modification to therapy may be appropriate in certain patients based on their genetic profile. As novel therapies become available, suitable controlled trials in children are essential for their safe use in this population and will ensure that children are not denied timely access to advances in treatment.
在过去的70年里，儿童急性淋巴细胞白血病已从一种生存率仅为4个月的致命疾病转变为一种85%以上患者可治愈的疾病。很明显，随着治疗强度的增加，更多的儿童被治愈，但代价是毒性增加，这对一些儿童来说可能会导致严重的长期发病甚至死亡。近年来的努力方向是识别疾病和治疗反应的敏感标志物，以便在不需要治疗的患者中减少治疗，而在需要治疗的患者中加强治疗。临床特征已被用于将患者分为不同的风险组，再加上在分子水平上跟踪反应，这在很大程度上实现了针对患者的个性化治疗。大量研究集中在白血病本身的分子特征上，以阐明该疾病以及某些类型白血病的相对或绝对耐药性背后的生物学机制。这些分子标志物还可以作为新疗法的靶点，而新疗法需要更新的试验方法来证明其效用。对患者生物学的关注较少，但很明显，一些患者比其他患者更容易受到不良事件和毒性的影响。通过使用药物基因组学，根据某些患者的基因特征对治疗进行调整可能是合适的。随着新疗法的出现，在儿童中进行适当的对照试验对于在该人群中安全使用这些疗法至关重要，并且将确保儿童不会被剥夺及时获得治疗进展的机会。
