Skärby T V Ch, Anderson H, Heldrup J, Kanerva J A, Seidel H, Schmiegelow K
Department of Pediatrics, Lund University Hospital, Lund, Sweden.
Leukemia. 2006 Nov;20(11):1955-62. doi: 10.1038/sj.leu.2404404. Epub 2006 Sep 21.
We explored the relationship between time to relapse and different exposure variables (serum methotrexate (S-MTX) 23, 36 and 42 h after start of administration, MTX elimination time and leucovorin (LV) dose) during high-dose MTX (HDM) treatment of 445 children with acute lymphoblastic leukemia. MTX was infused at 5 g/m2 (non-high risk) or 8 g/m2 (high risk) over 24 h, 2-9 times per patient. LV rescue dose was adjusted according to the S-MTX concentration. Time from end of the last HDM to relapse was analyzed by Cox regression analysis with the logarithms of S-MTX and LV dose as exposures. The combined results from all risk groups suggest that high LV dose is related to higher risk for relapse. Doubling of the LV dose increased the relapse risk by 22% (95% confidence interval 1-49%, P = 0.037). High LV doses correlated with high MTX levels at 23, 36 and 42 h and longer elimination time. The results suggest that high doses of LV increase the risk for relapse despite the fact that they were correlated with high MTX levels and longer MTX elimination time. The choice of MTX and LV doses may be regarded as an intricate balance between effect and counter-effect.
我们在445例急性淋巴细胞白血病患儿的大剂量甲氨蝶呤（HDM）治疗期间，探讨了复发时间与不同暴露变量（给药开始后23、36和42小时的血清甲氨蝶呤（S-MTX）、甲氨蝶呤消除时间和亚叶酸钙（LV）剂量）之间的关系。甲氨蝶呤以5 g/m²（低危）或8 g/m²（高危）的剂量在24小时内输注，每位患者输注2 - 9次。LV解救剂量根据S-MTX浓度进行调整。以S-MTX和LV剂量的对数作为暴露因素，通过Cox回归分析对从最后一次HDM结束到复发的时间进行分析。所有风险组的综合结果表明，高剂量LV与更高的复发风险相关。LV剂量翻倍使复发风险增加22%（95%置信区间1 - 49%，P = 0.037）。高剂量LV与23、36和42小时时的高甲氨蝶呤水平以及更长的消除时间相关。结果表明，尽管高剂量LV与高甲氨蝶呤水平和更长的甲氨蝶呤消除时间相关，但仍会增加复发风险。甲氨蝶呤和LV剂量的选择可被视为效应与反效应之间的一种复杂平衡。
