严重肠粘膜炎（IM）会增加急性淋巴细胞白血病（ALL）诱导治疗期间血流感染（BSI）和炎症毒性的风险。然而，IM 在缓解后的后续 ALL 治疗阶段中的影响仍然未知。本研究调查了 ALL 儿童在大剂量甲氨蝶呤 (HDMTX) 治疗期间 IM（通过血浆瓜氨酸和趋化因子 CCL20 测量）与 BSI 和全身炎症（通过 C 反应蛋白，CRP 反映）的发展之间的关系， ALL 巩固治疗的重要组成部分。该研究比较了根据 NOPHO ALL 2008 方案 (n = 52) 和 ALLTogether1 方案 (n = 42) 治疗的患者，两者均采用相同的 HDMTX 程序，但时间安排不同。 HDMTX 后一周，根据 NOPHO ALL 2008 和 ALLTogether1 方案治疗的患者，瓜氨酸中位水平分别降至 14.5 和 16.9μM（p=0.11）。在一项方案和中性粒细胞计数调整分析中，低瓜氨酸血症（<10μmol/L）与 HDMTX 3 周内 BSI 几率增加相关（OR==26.2，p=0.0074）。与根据 ALLTogether1 治疗的患者相比，根据 NOPHO ALL 2008 方案治疗的患者在 HDMTX 后表现出粘膜和全身炎症增加，CCL20（14.6 vs. 3.7 pg/mL，p< 0.0001）和 CRP 水平（10.0 vs. 10.0）增加。 1.0 毫克/升，p < 0.0001）。瓜氨酸和 CCL20 均与这些患者的 CRP 相关（分别为 rs = -0.44，p = 0.0016 和 rs = 0.35，p = 0.016）。这些结果表明，HDMTX 后的低瓜氨酸血症会增加 BSI 的风险，这证实了之前从更强化的治疗中观察到的结果。此外，这些数据表明，化疗后患者对粘膜炎和炎症毒性的脆弱性随治疗方案的不同而变化。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C-reactive protein, CRP) in children with ALL during high-dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post-HDMTX, citrulline dropped to median levels of 14.5 and 16.9 μM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count-adjusted analysis, hypocitrullinaemia (<10 μmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal- and systemic inflammation post-HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = -0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.