供体淋巴细胞输注联合伊马替尼治疗异基因造血干细胞移植后Ph+白血病复发的初步临床观察

Prospective trial of imatinib and donor leukocyte infusion for relapse of Ph positive leukemia after allogeneic stem cell transplantation

目的观察供体淋巴细胞输注(DLI)联合伊马替尼治疗异基因移植后复发的Ph^+白血病的疗效。方法以实时定量聚合酶链反应(RQ-PCR)及荧光原位杂交(FISH)方法检测5例Ph^+白血病患者移植后微小残留病灶(MRD),在复发早期进行DLI联合伊马替尼治疗。伊马替尼初始剂量300～400 mg/d,DLI采用递增剂量方案,首次剂量为0.5×10~6/kg～5×10~6/kg,间隔时间为1～4周。观察治疗反应及相关并发症。结果5例患者中有2例慢性髓细胞白血病(CML)患者发生分子学反应,其中1例达分子学缓解;而2例高危Ph^+急性淋巴细胞白血病(Ph^+ALL)患者及1例早期血液学复发的慢性髓细胞白血病第二次慢性期(CML-CP_2)患者治疗无反应。复发后随访40 d～14个月,5例应用伊马替尼后均未发生严重并发症。DLI后1例发生Ⅳ度急性移植物抗宿主病(aGVHD),2例发生Ⅰ～Ⅱ度aGVHD,1例发生肺部感染。结论伊马替尼联合DLI可有效治疗移植后复发的CML慢性期患者,副作用可耐受,但对复发的Ph^+ALL及CML急变期患者疗效有限。

Objective To study the effect of imatinib combined with donor leukocyte infusion (DLI) in the treatment of Ph positive leukemia after allogeneic stem cell transplantation.Methods 5 patients with early relapse after allogeneic stem cell transplantation were treated with imatinib and DLI.Imatinib was given orally at dose of 300～400 mg/d initially.DLI was performed at escalating dose (initial dose 0.5×10~6/kg～5×10~6/kg) with intervals of 1～4 weeks.Make observation of complications and evaluate treatment reactions.Re- suits Among 5 patients,2 chronic myelocytic leukemia(CML) patients acquired mocular response,1 of which achieved molecular remission;while 2 high-risk Ph positive acute lymphoblastic leukemia(Ph^+ALL) patients and 1 CML-CP2 (second chronic phase) patient with early hematologic relapse after SCT have minor response to therapy.During follow-up ranging from 40 days to 14 months,no severe complications associated with ima- tinib was observed in all patients.After DLI,Ⅰ～ⅡaGVHD was observed in 2 cases,ⅣaGVHD in 1 case,and severe pneumonia in 1 case.Conclusion Imatinib combined with DLI can be performed efficiently for re- lapse of CML-CP after allogeneic stem cell transplantation,with acceptable complications,but little effect was observed for the post-transplant relapse of Ph^+ALL and CML-Blast phase.