Ratio of methotrexate to folate uptake by lymphoblasts in children with B-lineage acute lymphoblastic leukemia: a pilot study.
Ratio of methotrexate to folate uptake by lymphoblasts in children with B-lineage acute lymphoblastic leukemia: a pilot study.
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B 系急性淋巴细胞白血病儿童的淋巴细胞摄取甲氨蝶呤与叶酸的比率：一项初步研究。
DOI：
10.1097/00043426-200005000-00007
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Kamen,BA
中科院分区：
文献类型：
--
作者：
Mantadakis,E;Smith,AK;Kamen,BA
目的：甲氨蝶呤（MTX）是治疗儿童急性淋巴细胞白血病（ALL）的最有效药物之一。由于MTX和5-甲基四氢叶酸（5CH 3 THF）共享摄取和代谢途径，MTX的疗效可能不仅取决于其代谢，还取决于淋巴母细胞对叶酸的累积程度。作者的目标是比较在体外叶酸和抗叶酸吸收B-系淋巴母细胞的患者谁仍然在持续完全缓解（CCR）和复发occurred.Patients和方法：24例儿童B-系ALL进行了研究，在诊断（n= 20）或复发（n= 4）。结果：截至1999年7月，16例确诊的患者在缓解后中位随访时间为45个月，仍留在CCR中。在复发时研究的两名患者处于第二CCR中;其余两名死于疾病进展。在诊断时研究的16例首次CCR患者和复发时研究的4例患者之间，[3 H] MTX和5 CH 3 [3 H] THF的中位摄取量均无显著差异。然而，中位比值[3 H] MTX：5CH 3 [3 H] THF的摄取显着不同的患者谁仍然在第一CCR与研究的患者在relations.Conclusions：[3 H] MTX的摄取在体外白血病淋巴母细胞的5CH 3 [3 H] THF可能与治疗结果在儿童B系ALL呈正相关。有必要对均匀治疗的患者进行更大规模的研究以证实这些结果。
Purpose:Methotrexate (MTX) remains one of the most effective drugs for the treatment of children with acute lymphoblastic leukemia (ALL). Because MTX and 5-methyltetrahydrofolate (5CH 3 THF) share uptake and metabolic pathways, the efficacy of MTX is likely to depend not only on its metabolism but also on how well folate is accumulated by lymphoblasts. The authors' goal was to compare in vitro folate and antifolate uptake in B-lineage lymphoblasts from patients who remained in continuous complete remission (CCR) and those in whom relapse occurred.Patients and Methods:Twenty-four children with B-lineage ALL were studied at diagnosis (n= 20) or relapse (n= 4). Lymphoblasts obtained by bone marrow aspiration were incubated for 24 hours in vitro with 0.05 μM 5CH 3 [3 H] THF or 1 μM [3 H] MTX.Results:As of July 1999, 16 patients studied at diagnosis remained in CCR at a median follow-up of 45 months after achieving remission. Two of the patients studied at relapse are in second CCR; the remaining two died from progressive disease. The median uptake of neither [3 H] MTX nor 5CH 3 [3 H] THF differed significantly between the 16 patients in first CCR studied at diagnosis and the 4 patients studied at relapse. However, the median ratio of [3 H] MTX: 5CH 3 [3 H] THF uptake differed significantly for patients who remained in first CCR versus patients studied at relapse.Conclusions:The uptake of [3 H] MTX in relation to 5CH 3 [3 H] THF by leukemic lymphoblasts in vitro may correlate positively with treatment outcome in children with B-lineage ALL. A larger study of homogeneously treated patients is necessary to confirm these results.