Styczynski J, Pieters R, Huismans D R, Schuurhuis G J, Wysocki M, Veerman A J
Department of Paediatric Haematology and Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Br J Haematol. 2000 Sep;110(4):813-8. doi: 10.1046/j.1365-2141.2000.02211.x.
The difference in the current cure rates between adult and childhood acute lymphoblastic leukaemia (ALL) may be caused by differences in drug resistance. Earlier studies showed that in vitro cellular drug resistance is a strong independent adverse risk factor in childhood ALL. Knowledge about cellular drug resistance in adult ALL is still limited. The present study compared the in vitro drug resistance profiles of 23 adult ALL patients with that of 395 childhood ALL patients. The lymphoblasts were tested by the MTT assay. The group of adult ALL samples was significantly more resistant to cytosine arabinoside, L-asparaginase, daunorubicin, dexamethasone and prednisolone. The resistance ratio (RR) was highest for prednisolone (31.7-fold) followed by dexamethasone (6.9-fold), L-asparaginase (6. 1-fold), cytosine arabinoside (2.9-fold), daunorubicin (2.5-fold) and vincristine (2.2-fold). Lymphoblasts from adult patients were not more resistant to mercaptopurine, thioguanine, 4-HOO-ifosfamide, mitoxantrone and teniposide. There were no significant differences in drug resistance between adult T-cell (T-) ALL (n = 11) and adult common/pre-B-cell (B-) ALL (n = 10). Additionally, adult T-ALL did not differ from childhood T-ALL (n = 69). There were significant differences between adult common/pre-B-ALL and childhood common/pre-B-ALL (n = 310) for prednisolone (RR = 302, P = 0.008), dexamethasone (RR = 20.9, P = 0.017) and daunorubicin (RR = 2.7, P = 0.009). Lymphoblasts from adults proved to be relatively resistant to drugs commonly used in therapy. This might contribute to the difference in outcome between children and adults with ALL.
成人与儿童急性淋巴细胞白血病（ALL）当前治愈率的差异可能是由耐药性差异所致。早期研究表明，体外细胞耐药性是儿童ALL中一个强大的独立不良风险因素。关于成人ALL细胞耐药性的知识仍然有限。本研究比较了23例成人ALL患者与395例儿童ALL患者的体外耐药谱。通过MTT法检测淋巴母细胞。成人ALL样本组对阿糖胞苷、L-天冬酰胺酶、柔红霉素、地塞米松和泼尼松龙的耐药性明显更高。泼尼松龙的耐药比（RR）最高（31.7倍），其次是地塞米松（6.9倍）、L-天冬酰胺酶（6.1倍）、阿糖胞苷（2.9倍）、柔红霉素（2.5倍）和长春新碱（2.2倍）。成人患者的淋巴母细胞对巯嘌呤、硫鸟嘌呤、4 - HOO - 异环磷酰胺、米托蒽醌和替尼泊苷的耐药性并不更高。成人T细胞（T -）ALL（n = 11）和成人普通/前B细胞（B -）ALL（n = 10）之间在耐药性方面无显著差异。此外，成人T - ALL与儿童T - ALL（n = 69）也无差异。成人普通/前B - ALL与儿童普通/前B - ALL（n = 310）在泼尼松龙（RR = 302，P = 0.008）、地塞米松（RR = 20.9，P = 0.017）和柔红霉素（RR = 2.7，P = 0.009）方面存在显著差异。事实证明，成人的淋巴母细胞对治疗中常用药物具有相对耐药性。这可能导致ALL儿童和成人在治疗结果上存在差异。
