COALL-97方案治疗急性淋巴细胞白血病临床及实验室研究

Therapy and Research of Acute Lymphoblastic Leukemia in Childhood with Cooperative Acute Lymphoblastic Leukemia Group-97

目的 引用德国儿童急性淋巴细胞白血病协作组 (cooperativeALLstudygroup ,COALL)的COALL 97方案治疗急性淋巴细胞白血病 (ALL) ,从临床疗效防治及目前国内外选用有效治疗ALL的药物 ,左旋门冬酰胺酶 (L Asp)的药代动力学方面 ,探讨在我国治疗儿童ALL的最佳方案及L Asp的最佳给药方式。方法 ALL患儿 1 2例自愿接受COALL 97方案在我院完成早期强化治疗后 ,回当地继续口服巯基嘌呤 (6 MP) /硫鸟嘌呤 (6 TG)加甲氨蝶呤 (MTX)持续治疗 ,每隔 3个月、半年来院复查 ,总疗程 1 .5～ 2 .0年。结果 诱导治疗后d1 4做骨髓检查 8例呈缓解骨髓像 ,治疗 2 8d后 1 2例均完全缓解 (CR) ,CR率1 0 0 % ,HR ALL患儿 1例CR后 1 0个月时骨髓复发并重症感染死亡。应用高压液相色谱技术 (HR HPLC)检测 1次注射 40 0 0 0U/m2 L Asp后能使血清和脑脊液 (CSF)中门冬酰胺 (ASN)浓度降低 ,并持续至第 5周后回升。 结论 COALL 97方案可被我国ALL患儿所接受 ;在治疗ALL的临床实践中 ,该方案确有可借鉴之处 ;1次 / 2～ 6周静脉注射 40 0 0 0U/m2 L Asp联合化疗的用药方式不仅作用强、持续时间长 ,耐药性小、不良反应少 ,且避免患儿每天或隔天静脉注射痛苦及患儿家长的经济和精神负担。

Objective To investigate the more effective protocol for childhood with acute lymphoblastic leukemia(ALL) and to search for a safer and more effective way with L-asparaginase (L-ASP) as the main drug in combination protocol.Methods Twelve diagnostic children with ALL received the therapy and were administered in German protocol of cooperative acute lymphoblastic leukemia group(COALL)-97.After early intensive chemotherapy in our hospital, these children went back home and with the drug 6-MP/6-TG and MTX oral for maintenance therapy(MT) and reexamined for every 3-6 months, the whole course was 1.5 to 2 years.Results Eight children′s bone marrow tests were remission on the 14 th day after induced therapy and 12 children were complete remission (CR) on the 28 th day,with CR rate 100%. One child with HR_HPLC whose bone marrow relapse ten months after CR,died of serious infection.Asparagine(ASN) concentrations were depleted from 0-5 week after the administration of high-dose 40 000 U/(m2·time) L-ASP by intravenous injection in blood serum and CSF.Conclusions The protocol of COALL-97 might be accepted by Chinese children with ALL. The combination chemotherapy protocol which includes high-dose intravenous injection L-ASP 40 000 U/(m2·time) for each 4-6 weeks has many advantages, not only has strong action, low drug resistance, low toxicity, but also may avoid injection pain of vein everyday and lower the burden of the parents economically and psychologically.