慢性粒细胞白血病患者异基因造血干细胞移植后不同干预方案疗效的比较研究

A comparative study of different intervention regimens for chronic myelogenous leukemia post allogeneic hematopoietic stem cell transplantation

目的 了解免疫调节治疗和伊马替尼用于慢性粒细胞白血病（CML）异基因造血干细胞移植后早期预防复发的有效性、安全性.方法 2004年11月至2008年11月行造血干细胞移植的CML患者64例,根据bcr-abl监测结果,在移植后早期进行了干预治疗,方案为免疫调节、伊马替尼单独及与免疫调节联合.免疫调节干预包括减停免疫抑制剂和采用改良的供者淋巴细胞输注（mDLI）.伊马替尼干预组13例,免疫凋节治疗组20例、联合治疗组31例.比较不同治疗组的近期疗效和远期疗效及不良反应.结果 伊马替尼治疗组、免疫调节治疗组、联合治疗组患者bcr-abl融合基因转阴率分别为86.0%、90.0%和83.9%（P=0.126）;4年累计白血病血液学复发率分别为32.3%、0和16.1%（P=0.130）,单独应用伊马替尼组比免疫调节治疗组复发率有增高的趋势（P=0.052）;三组患者4年存活率分别为90.0%、89.7和83.0%（P=0.696）.三组间的不良反应有明显差异,伊马替尼治疗组的血液学不良反应发生率高于免疫调节治疗组,与联合治疗组相近（分别为30.8%、5.0%和38.7%,P=0.001）,而GVHD发生率在三组患者中的任意两组间均有差异,免疫调节治疗组、伊马替尼治疗组和联合治疗组分别为95.0%、0和67.7%（P=0.000）.减停CsA患者中1例发生排斥,2例死于重度GVHD或GVHD后感染,治疗相关死亡率10%.其他两组无治疗相关的直接死亡者.结论 三种治疗方案可以达到相似的疗效,但不良反应不同,应权衡并进行个性化选择,减停CsA对早期患者风险较大不宜作为初始治疗的首选,单独采用伊马替尼治疗的长期效果有待进一步观察.治疗方案的细化和优化有待进一步前瞻性对照研究.

Objective To study the efficacy and safety of immunotherapy and imatinib mesylate used in early post allogeneic hematopoietic stem cell transplantation （HSCT） for intervention. Methods Sixtyfour chronic myelogenous leukemia（CML） patients received HSCT were analyzed retrospectively based on bcrabl kinetics post HSCT. Patients were divided into three groups, imatinib group （n = 13 ）, immunotherapy group（n =20）and combining both group（ n = 31 ）. The primary endpoint is molecular response, the second endpoint is side effect related to intervention. Results There was no difference among the three groups in converting to bcr-abl negativity （86.0%, 90.0% and 83.9%, respectively, P = 0. 126）, 4 years cumulative relapse incidence （32.3% ,0% and 16.1%, respectively, P = 0. 130）and 4 years OS （90.0% ,89.7%,83.0%, respectively, P= 0.696）. There was a trend of more relapse in Imatinib group than in immunotherapy group（P = 0.052）. There were more hematological toxicity in imatinib and combining groups than that in immunotherapy group （30.8%, 38.7%, and 5.0%, respectively, P =0. 001 ）. There was significant difference in the incidence of GVHD among the three groups（ P =0.000）, being 95.0%, 0% and 67.7% in immunotherapy, imatinib and combining groups, respectively. Intervention related death occurred in 2 cases,both with discontinuation of CsA, graft failure in another patient with CsA withdrawal. No intervention related death occurred in the other two groups. Conclusions All three regimens can give a quick and durable molecular remission in most of the patients, but side effects are different. The choice of regimen should be balanced with toxicity individually. CsA withdrawal is not the best choice for very early intervention,the longterm effect for patients received imatinib alone without GVHD is needed to be studied.