Nygren P, Kristensen J, Jonsson B, Sundström C, Lönnerholm G, Kreuger A, Larsson R
Department of Oncology, University Hospital, University of Uppsala, Sweden.
Leukemia. 1992 Nov;6(11):1121-8.
The automated fluorometric microculture cytotoxicity assay (FMCA) was used for chemotherapeutic drug sensitivity testing of fresh and cryopreserved tumor cells from patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse. The technique success rate was 87% for fresh and 81% for cryopreserved samples. Up to 16 different cytotoxic drugs were routinely tested, but neither asparaginase nor methotrexate produced dose-response related cell kill. FMCA data showed good correlation to the well established Disc assay and the drug sensitivity reported by the FMCA was in good agreement with known clinical activity. Samples from children and initial ALL tended to be more drug sensitive than those from adults and ALL at relapse, respectively. For 36 samples clinical outcome was correlated to the quartile position in comparison to all other samples for the most in vitro active drug actually given to the patient. For patients with samples in the first, second, third, and fourth quartiles, the probabilities of complete remission were 89, 57, 38, and 0%, respectively. Using the median value as cut-off line, the sensitivity and specificity of the assay were 87 and 62%, respectively. It is concluded that the FMCA with a minimum of effort and with high success rate report clinically relevant drug sensitivity profiles for ALL.
采用自动荧光微量培养细胞毒性试验（FMCA）对急性淋巴细胞白血病（ALL）患者诊断及复发时的新鲜和冻存肿瘤细胞进行化疗药物敏感性检测。新鲜样本的技术成功率为87%，冻存样本为81%。常规检测多达16种不同的细胞毒性药物，但门冬酰胺酶和甲氨蝶呤均未产生与剂量相关的细胞杀伤作用。FMCA数据与成熟的纸片扩散法显示出良好的相关性，且FMCA报告的药物敏感性与已知临床活性高度一致。儿童ALL初发时的样本往往比成人ALL复发时的样本对药物更敏感。对于36份样本，将临床结局与给予患者的实际体外活性最高的药物相比，与所有其他样本的四分位数位置相关。对于四分位数处于第一、第二、第三和第四位的患者，完全缓解的概率分别为89%、57%、38%和0%。以中位数作为截断值，该试验的敏感性和特异性分别为87%和62%。结论是，FMCA只需付出最少努力且成功率高，可为ALL报告具有临床相关性的药物敏感性概况。
