Schmiegelow K, Schrøder H, Schmiegelow M
Department of Pediatrics, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Cancer Chemother Pharmacol. 1994;34(3):209-15. doi: 10.1007/BF00685079.
In a consecutive study of 14 boys and 17 girls with non-B-cell ALL who were > or = 1 year of age at diagnosis, the degree of myelosuppression during the last year of MTX/6MP maintenance therapy was analyzed in relation to the erythrocyte concentration of MTX polyglutamates and 6-thioguanine nucleotides (E-MTX and E-6TGN, the respective major cytotoxic metabolites of MTX and 6MP). For each patient, E-MTX and E-6TGN levels were measured 2-15 (median, 6) and 2-17 (median, 7) times, respectively. From these measurements, arithmetic means of E-MTX and E-6TGN were calculated (mE-MTX and mE-6TGN, respectively). Since MTX and 6MP probably work synergistically, the product of mE-MTX and mE-6TGN was calculated for each patient (mE-MTX x 6TGN). The degree of myelosuppression was registered as the mean WBC determined following cessation of the therapy minus the mean WBC measured during the therapy (mWBCshift). The mean WBCs measured on therapy (mWBC(on)) and off therapy were highly correlated (r = 0.48, P = 0.009). The median mWBCshift was 2.7 x 10(9)/l (range, 1.4-4.8 x 10(9)/l). In a multivariate regression analysis, the best-fit model to predict the mWBCshift included mE-MTX x 6TGN, age at drug withdrawal, and mWBC in the order given [mWBCshift = 4.3 + 0.00089 x (mE-MTX x 6TGN) - 0.097 x age - 0.41 x mWBC(on); global rs = 0.66, P = 0.0002]. Thus, the patients with higher mE-MTX x 6TGN values, the younger patients, and the patients with the lowest WBC during therapy had the most pronounced degree of myelosuppression as measured by mWBCshift. These results indicate that E-MTX and E-6TGN may give a better reflection of the treatment intensity than do the WBCs alone.
在一项针对14名男孩和17名女孩的连续性研究中，这些被诊断为非B细胞急性淋巴细胞白血病（ALL）且诊断时年龄≥1岁的患儿，对甲氨蝶呤（MTX）/6-巯基嘌呤（6MP）维持治疗最后一年期间的骨髓抑制程度，与MTX多聚谷氨酸盐和6-硫鸟嘌呤核苷酸的红细胞浓度（分别为E-MTX和E-6TGN，它们是MTX和6MP各自主要的细胞毒性代谢产物）进行了分析。对于每位患者，E-MTX和E-6TGN水平分别测量了2 - 15次（中位数为6次）和2 - 17次（中位数为7次）。根据这些测量值，计算出E-MTX和E-6TGN的算术平均值（分别为mE-MTX和mE-6TGN）。由于MTX和6MP可能具有协同作用，计算了每位患者的mE-MTX与mE-6TGN的乘积（mE-MTX×6TGN）。骨髓抑制程度记录为治疗停止后测定的平均白细胞计数减去治疗期间测量的平均白细胞计数（mWBCshift）。治疗期间（mWBC(on)）和治疗停止后测量的平均白细胞计数高度相关（r = 0.48，P = 0.009）。mWBCshift的中位数为2.7×10⁹/L（范围为1.4 - 4.8×10⁹/L）。在多变量回归分析中，预测mWBCshift的最佳拟合模型按给定顺序包括mE-MTX×6TGN、停药时年龄和mWBC（mWBCshift = 4.3 + 0.00089×(mE-MTX×6TGN) - 0.097×年龄 - 0.41×mWBC(on)；总体rs = 0.66，P = 0.0002）。因此，mE-MTX×6TGN值较高的患者、年龄较小的患者以及治疗期间白细胞计数最低的患者，以mWBCshift衡量的骨髓抑制程度最为明显。这些结果表明，与单独的白细胞计数相比，E-MTX和E-6TGN可能能更好地反映治疗强度。
