Zając-Spychała Olga, Wachowiak Jacek
Klinika Onkologii, Hematologii i Transplantologii Pediatrycznej UM w Poznaniu, ul. Szpitalna 27/33, 60-572 Poznań, Poland.
Med Wieku Rozwoj. 2012 Apr-Jun;16(2):128-37.
Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in combination with high doses of intravenous methotrexate.
急性淋巴细胞白血病是儿童中最常见的恶性肿瘤。目前用于治疗儿童急性淋巴细胞白血病的所有治疗方案都包括中枢神经系统预防。最初人们认为中枢神经系统预防的最佳方法是放射治疗。但尽管这种方法有效，但可能会导致晚期后遗症和并发症。在波兰目前用于治疗急性淋巴细胞白血病的方案中，预防性放射治疗剂量已减少50%（至12 Gy），仅用于分层为高危组的患者以及诊断为T细胞急性淋巴细胞白血病（T-ALL）的患者。作为放射治疗的补充，鞘内注射甲氨蝶呤单独使用或与阿糖胞苷联合使用，并给予氢化可的松，同时还给予高剂量或中剂量的静脉注射甲氨蝶呤进行全身化疗（取决于风险组和白血病免疫表型）。最近的研究表明，中枢神经系统的高剂量照射会损害认知发展，导致记忆力减退、视觉运动协调障碍、注意力紊乱和智商降低。已经证明，认知障碍的程度取决于针对内侧颞叶结构，特别是海马体及其周围皮质的辐射剂量。此外，高剂量静脉使用的甲氨蝶呤会干扰叶酸代谢，而叶酸是中枢神经系统中神经元正常发育和最佳功能所必需的。已经证明，接受高剂量甲氨蝶呤治疗的患者具有记忆技能下降和智商较低的特征。关于长期神经解剖学异常和神经心理学缺陷的文献数据并不明确，目前仍没有关于低剂量照射与高剂量静脉甲氨蝶呤联合进行中枢神经系统预防方法的数据。
