急性淋巴细胞白血病TPMT基因多态性的研究

Study of TPMT Polumorphism of Children with Acute Lymphoblastic Leukemia

目的分析急性淋巴细胞白血病TPMT基因多态性与6-MP不良反应的相关性。方法收取急性淋巴细胞白血病患儿48例作为研究对象,对其TPMT基因型及6-MP不良反应进行分析。结果 48例患儿中31.25%按照常规6-MP使用剂量完成维持治疗,68.75%患儿出现不耐受后调整为低剂量完成维持治疗。常规剂量组重度不良反应发生率高于低剂量组,但差异无统计学意义(P>0.05)。6-MP所致骨髓抑制及肝功能损害发生率分别为93.75%及83.33%。仅有1例患儿发生杂合型TPMT×3C点突变,突变发生率为2.08%,该患儿同时发生4级骨髓抑制及4级肝功能损害。结论 TPMT×3C基因突变可能与6-MP所致重度不良反应有关,但6-MP所致重度不良反应可能是多种因素共同作用的结果。

Objective To analyze the relationship between TPMT polumorphism with 6-MP adverse reaction of children with acute lymphoblastic leukemia （ALL）. Methods 48 children with ALL were selected. TPMT polumorpbism and adverse reaction of 6-MP were observed and their relationship was analyzed. Results 31.25 % of 48 children were completed maintenance treatment using normal dose of 6-MP,68.75% of 48 children were completed maintenance treatment using low dose. Severe adverse reaction rate of normal dose group was higher than low dose group, but they had no statistically significance （ P 〉 0.05 ）. Myelosuppression rate and liver damage rate were 93.75% and 83.33% reapectively. There was only 1 case of hybrid TPMT × 3C point mutation, the mutation rate was 2.08%. Grade 4 myelosuppression and liver damage were occurred on this mutation case. Conclusion TPMT × 3C mutation may have relations with severe adverse reaction of 6-MP. But the adverse reactions may be caused by muhiple effect factors.