Cheng K K-F
The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong.
Eur J Cancer Care (Engl). 2008 May;17(3):306-11. doi: 10.1111/j.1365-2354.2007.00843.x.
Oral mucositis is a major toxicity associated with high-dose methotrexate (HD-MTX) therapy in the treatment of children with acute lymphoblastic leukaemia and osteosarcoma. This pilot matched case-control study investigated the associations between plasma concentration of MTX at 42 (p-MTX(42h)) and 66 (p-MTX(66h)) h, absolute neutrophil count (ANC) < or = or >1.0 x 10(9)/l, serum transaminases (ASAT/ALAT) < or > or =58 U/l, WHO < or > or =grade 2 nausea/vomiting and WHO < or > or =grade 2 oral mucositis. In this study, 11 children with WHO > or =grade 2 oral mucositis were compared with 17 control children matched for age, diagnosis and MTX-dosage. The results indicated that children with p-MTX(42h) > or = 1.0 micromol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p-MTX(42h) < 1.0 micromol/l. Children with p-MTX(66h) >= 0.2 micromol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p-MTX(66h) < 0.2 micromol/l. Children with ANC < or = 1.0 x 10(9)/l had an OR of 1.2 of developing oral mucositis when compared with the referent group of children who had ANC > 1.0 x 10(9)/l. In comparison with the referent group of children, who had <58 U/l ASAT/ALAT, those with ASAT/ALAT > or = 58 U/l had an OR of 1.2 of developing oral mucositis. Finally, children with WHO grade > or =2 nausea/vomiting had an elevated risk of developing oral mucositis when compared with the referent group of children who had WHO grade <2 nausea/vomiting (OR = 8.7). In conclusion, the results in this preliminary study provide support for the hypothesis that the risk of oral mucositis is associated with the plasma MTX concentration at 66 h and the level of nausea/vomiting.
口腔黏膜炎是大剂量甲氨蝶呤（HD-MTX）治疗急性淋巴细胞白血病和骨肉瘤患儿时的一种主要毒性反应。这项配对病例对照试验研究了42小时（p-MTX(42h)）和66小时（p-MTX(66h)）时甲氨蝶呤的血浆浓度、绝对中性粒细胞计数（ANC）≤或＞1.0×10⁹/L、血清转氨酶（ASAT/ALAT）≤或＞或=58 U/L、世界卫生组织（WHO）≤或＞或=2级恶心/呕吐以及WHO≤或＞或=2级口腔黏膜炎之间的关联。在本研究中，将11名WHO≥2级口腔黏膜炎患儿与17名年龄、诊断和甲氨蝶呤剂量相匹配的对照患儿进行了比较。结果表明，与p-MTX(42h)＜1.0 μmol/L的参照组患儿相比，p-MTX(42h)≥1.0 μmol/L的患儿发生口腔黏膜炎的比值比（OR）为4.3。与p-MTX(66h)＜0.2 μmol/L的参照组患儿相比，p-MTX(66h)≥0.2 μmol/L的患儿发生口腔黏膜炎的OR为8.2。与ANC＞1.0×10⁹/L的参照组患儿相比，ANC≤1.0×10⁹/L的患儿发生口腔黏膜炎的OR为1.2。与ASAT/ALAT＜58 U/L的参照组患儿相比，ASAT/ALAT≥58 U/L的患儿发生口腔黏膜炎的OR为1.2。最后，与WHO ＜2级恶心/呕吐的参照组患儿相比，WHO≥2级恶心/呕吐的患儿发生口腔黏膜炎的风险升高（OR = 8.7）。总之，这项初步研究的结果为口腔黏膜炎风险与66小时时的血浆甲氨蝶呤浓度及恶心/呕吐程度相关这一假说提供了支持。
