达沙替尼联合甲氨蝶呤和左旋门冬酰胺酶挽救性治疗费城染色体阳性急性淋巴细胞白血病致重度药物性肝损伤一例并文献复习

Dasatinib combined with methotrexate and L-asparaginase in the treatment of patients with Philadelphia chromosome positive acute lymphoblastic leukemia cause severe drug-induced liver injury： one case report and literature review

目的提高对达沙替尼联合大剂量甲氨蝶呤（HD-MIX）和左旋门冬酰胺酶（L-Asp）方案挽救性治疗费城染色体阳性急性淋巴细胞白血病（Ph^＋ALL）致重度药物性肝损伤的认识。方法报道达沙替尼联合HD-MTX及L-Asp方案挽救性治疗Ph^＋ALL致重度药物性肝损伤1例并文献复习。结果此例Ph^＋ALL患者在该方案化疗后第7天暴发重度药物性肝损伤，肝功能：总胆红素（TBIL）221．7μmol／L，直接胆红素（DBIL）156．1μmol／L，间接胆红素（IBIL）65．6μ mol／L，丙氨酸氨基转移酶（ALT）111U／L，天冬氨酸氨基转移酶（AST）131U／L，碱性磷酸酶（ALP）354U／L，谷氨酰转肽酶（GGT）256U／L，总胆汁酸（TBA）199．2μmol／L。经积极保肝治疗2周后，胆红素及氨基转移酶降至正常，且疾病达完全缓解。结论达沙替尼联合HD-MTX及L-Asp方案挽救性治疗Ph^＋ALL疗效显著，但三药均有明显肝脏毒性，联合使用时应注意暴发性药物性肝损伤的发生。

Objective To improve the cognition of sever liver injury of treating Philadelphia positive acute lymphoblastic leukemia （Ph＋ ALL） with salvage chemotherapy of dasatinib combined with high-dose methotrexate （HD-MTX） and L-asparaginase （L-Asp）. Methods Severe drug-induced liver injury caused by dasatinib with HD-MTX and L-Asp in one patient with Ph^＋ ALL was reported. Results Severe drug-induced liver injury happened on the seventh day after treatment, TBIL 221.7 μmol/L, DBIL 156.1 μmol/L, IBIL 65.6 μ mol/L, ALT 111 U/L, AST 131 U/L, ALP 354 U/L, GGT 256 U/L, TBA 199.2 μmol/L. Through proper treatment, the patient recovered quite good, and the patient achieved complete remission after this chemotherapy. Conclusion Salvage chemotherapy which contains dasatinib, MTX and L-Asp can be effectively used in Ph^＋ ALL, but they are all of the hepatotoxieity, so drug-induced liver injury may happen while they are used together.