Styczynski Jan, Gil Lidia, Derwich Katarzyna, Wachowiak Jacek, Balwierz Walentyna, Badowska Wanda, Krawczuk-Rybak Maryna, Matysiak Michal, Wieczorek Maria, Balcerska Anna, Sonta-Jakimczyk Danuta, Stefaniak Jolanta, Kowalczyk Jerzy, Urasinski Tomasz, Sobol Grazyna, Komarnicki Mieczyslaw, Wysocki Mariusz
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland.
Anticancer Res. 2009 May;29(5):1643-50.
Clofarabine is a second-generation nucleoside analogue. The aim of the study was the analysis of ex vivo activity of clofarabine and 14 other anticancer drugs in pediatric and adult acute lymphoblastic (ALL) and myeloid (AML) leukemia.
The ex vivo drug resistance profile was analyzed in 282 patients, including 201 children with ALL de novo, 24 children with relapsed ALL, 25 children with AML de novo and 32 adults with AML. Cellular ex vivo drug resistance was tested by means of the MTT assay.
Clofarabine had comparable ex vivo activity against lymphoblasts and myeloblasts, both on initial diagnosis and at relapse, both in children and in adults. Its activity in acute myeloid leukemia was independent of patient age. No significant differences in drug resistance to clofarabine between pediatric age-based subgroups of ALL were detected, while it was observed for most of other drugs. An activity of clofarabine in relapsed pediatric ALL patients was as good as in newly-diagnosed ones.
In comparison to childhood acute lymphoblastic leukemia, lack of differences in ex vivo activity gives rationale for use of clofarabine in refractory and relapsed pediatric and adult patients with acute myeloid leukemia.
氯法拉滨是第二代核苷类似物。本研究旨在分析氯法拉滨及其他14种抗癌药物对儿童和成人急性淋巴细胞白血病（ALL）及急性髓细胞白血病（AML）的体外活性。
对282例患者的体外耐药情况进行分析，其中包括201例初发ALL儿童、24例复发ALL儿童、25例初发AML儿童及32例AML成人患者。采用MTT法检测细胞的体外耐药性。
氯法拉滨对淋巴细胞和髓细胞的体外活性在初诊及复发时，无论儿童还是成人，均具有可比性。其在急性髓细胞白血病中的活性与患者年龄无关。未检测到ALL不同儿童年龄亚组对氯法拉滨耐药性的显著差异，而其他大多数药物则有此差异。氯法拉滨在复发儿童ALL患者中的活性与新诊断患者相当。
与儿童急性淋巴细胞白血病相比，体外活性无差异为氯法拉滨用于难治性及复发的儿童和成人急性髓细胞白血病患者提供了依据。
