大剂量甲氨喋呤治疗小儿急性白血病时两种水化、碱化方法的比较

目的 进一步降低大剂量甲氨喋呤(HD-MTX)治疗小儿急性淋巴细胞白血病(ALL)时的毒副作用。方法 通过在HD-MTX治疗时应用两种不同的水化、碱化方法,观察其尿酸碱反应(pH值)、MTX的血清浓度、治疗效果及毒副作用的发生率。结果 (1)尿pH值的检测结果:A组共检测456例次,其中pH值<7为28例次,检出率为6.14％。B组共检测672例次,其中pH值<7为18例次,检出率为2.68％。两组相比较有显著性差异(X2=8.323,P<0.01)。(2)≥Ⅲ级毒副作用的发生率:A组:19例患儿共30例次,占29.7％。B组:28例患儿共16例次,占14.29％。两组相比较有显著性差异(X2=7.445,P<0.01)。(3)两组在用HD-MTX开始后44 h、68 h时MTX浓度异常者分别为7例次、5例次和5例次、2例次,两者相比较有差异(X244h=4.165,X268h=5.245,P<0.05)。(4)两组结果:A组:随访13-24个月,平均18.54±3.28月,13例(68.42％)处于完全缓解中且无髓处白血病的发生,复发4例,死亡1例,失访1例。B组:随访13-25个月,平均19.05±3.40月,22例(78.57％)处于完全缓解中且无髓外白血病的发生,失访1例,复发4例,1例因BUN升高改用HD-Ara-C。两组比较无显著性差异(X2=0.613,P<0.01)。结论 B组碱化、水化方法优于A组方法。

Comparative method on the difference of two different ways for hydration and alkalization in the treatment of childhood acute lymphoblastic leukemia with high - dose methotrexate

Objective To further reduce the toxic side - effects of the HD-MTX in the treatment of childhood acute lymphoblastic leukemia. Methods Two different ways for hydration and alkalization designed in the course of HD - MTX to evaluate the treatment results, Monitor the dynamic changes of the serum MTX level and occurrence of the toxic side - effects. Results The results showed (1) These are the results of pH value of urine; There were 456 samples tested in group A, Among them, those pH value less than 7 appear 28 times (4.16%). In contrast, 672 samples were tested in group B, it shows that 18 of 672 (2.68%) were pH value less than 7. These data given statistical test, shows a obvious difference exist. (X2= 8.323, P < 0.01) . (2) 101 episodes of the toxic side - effects were found in 19 patients in group A. of them, 25 times of leukocytopenia, 15 times of hemoglobin level decreasing. 12 times of thrombocytopenia, mucositis 24 times and skin rash 7 times. Over Ⅲ grade of severity in this group occurred in 30 times. Whereas in group B, 122 times of episodes happened in 28 cases. Leukocytopenia 18 times, hemoglobin level decreasing 13 times,thrombocytopenia 9 times, mucositis 30 times and skin rash 4 times. Over Ⅲ grade of severity, side - effects in this group happened in 16 times. So in comparison with the above toxic side - effects occurred in both groups, significant difference could be found (P < 0.01), (3) In group A. 10 times of liver function abnormalities and 8 times of gastro - intestinal side - effects occurred; Whereas in group B, 8 times and 19 times happened respectively with no significance existed in these two group (4) But, blood urea nitrogen (BUN) increased in 2 cases in group B with no one happened in group A: (5) The occurrence of the serum MTX level abnormalities in 44, and 68 hours of HD - MTX treatment appeared in both groups as following, in group A, 7 times and 5 times whereas in group B, 5 times and 2 times separately with some difference in these two groups (P < 0.05). (6) The results of the following- up in these two groups as following, in group A in addition to 1 case died, 1 case lost following- up and 4 case relapsed; other 13 case (68.42%) have kept on following - up for 13 - 24 months (the mean following- up time for 18.5±3.28 months) without any evidence of extramedullary involvement, whereas, in group B, 1 case lost follow - up, 4 cases relapsed and HD - MTX alterated with HD - Ara- c in one case who had BUN level increasing, 22 cases remained (78.57%) have kept on follow- up for 13-25 months (the mean follw- up time: 19.05±3.40 months with no evidence of extramedullary involevement) , so, there's no significant difference in comparison with the results from this two group (X2 = 0.613, P > 0.05) . Conclusion It indicated the protocol for hydration and alkalization in group B had greater advantage than that of group A in reducing the toxic side - effects.