异基因造血干细胞移植治疗伴T315 I突变的慢性髓系白血病的疗效观察

Allo-geneic hematopoietic stem cell transplantation in treatment with T315I mutation of chronic myelogenous leukemia

目的：探讨异基因造血干细胞移植（ allo-HSCT）治疗伴T315I突变的慢性髓系白血病（ CML）的临床疗效。方法回顾性分析2012年6月至2014年1月在安徽省立医院接受allo-HSCT治疗的4例伴T315I突变的CML患者资料。4例患者中男2例,女2例,年龄26～45岁；加速期2例,慢性期2例；2例行HLA相合同胞异基因外周血造血干细胞移植（ allo-PBSCT）,2例行单份HLA不全相合非血缘脐血造血干细胞移植（ UCBT）。移植前患者均无脾脏肿大,其中1例同时伴有F317L突变。4例患者移植前均接受伊马替尼治疗,从用药至发生T315I突变的时间为20～35个月。所有患者均采用清髓性预处理方案,环孢素 A 联合吗替麦考酚酯预防移植物抗宿主病（ GVHD ）。结果4例患者全部获得髓系植入,中性粒细胞绝对值≥0．5＆#215;109/L的时间为移植后第10～28天；1例因严重肺部感染于移植后第88天死亡,血小板未植入,另外3例患者血小板≥20＆#215;109/L的时间为移植后第15～33天。4例患者移植后第30天骨髓DNA短串联重复序列PCR检测均为100%供者型。1例UCBT患者发生植入前综合征；1例allo-PBSCT患者于移植后第12天出现皮肤Ⅰ度急性GVHD,经加用甲泼尼龙治疗后症状控制。3例可评估的患者中,1例发生慢性GVHD。移植后采用PCR定量技术密切监测患者BCR/ABL融合基因,全部患者移植后第30天BCR/ABL融合基因转阴,截止随访终点,除1例死亡外,余3例均未复发,无病生存时间分别为133、248、704 d。结论 allo-HSCT是目前治疗伴T315I突变的CML的有效方案,对没有同胞相合的供者,脐血也可作为理想的替代供者。

Objective To explore the therapeutic efficacy of allo-geneic hematopoietic stem cell transplantation （ allo-HSCT ） for chronic myelogenous leukemia （ CML ） patients with T315I mutation. Methods Retrospective analyses were conducted for 4 patients with T315I mutation of CML undergoing allo-HSCT from June 2012 to January 2014, including 2 cases in acceleration phase and 2 in chronic phase. There were 2 males and 2 females with ages from 26 to 45 years. Two patients received HLA-matched sibling allo-geneic peripheral blood stem cell transplantation （ allo-PBSCT ） while another 2 unrelated cord blood stem cell transplantation （UCBT）. No splenomegaly was found before transplantation. One case had F317L mutation. All of them were treated with imatinib before transplantation. And the time from medication to T315I mutation was 20 -35 months. All of them were conditioned with myeloablative regimen and received a combination of cyclosporine A （ CsA ） and mycophenolate mofetil （ MMF ） for preventing graft-versus-host disease （ GVHD） . Results Myeloid implantation was achieved in all of them. The time of absolute neutrophil count （ ANC） ≥0. 5 ＆#215; 109/L were 10-28 days. One patient whose platelet was not implanted died from severe pulmonary infection at Day 88 post-transplantation. For 3 patients, platelet≥20 ＆#215; 109/L were 15-33 days. But the marrow short tandem repeat （ STR）-PCR was 100% donor type at the time of 30 days post-transplantation in all patients. One case of UCBT developed pre-implantation immune response syndrome （ PES） and one acute GVHD of gradeⅠ at Day 12 after allo-PBSCT. However both were controlled after treatment with methylprednisolone. And 1/3 evaluatable patients developed chronic GVHD. BCR/ABL transcript was detected by qualitative PCR after transplantation. And all BCR/ABL fusion genes turned negative after 30 days of transplantation. Up to the follow-up endpoint, there was no relapse except for one mortality. And the time of disease-free survival was 133, 248 and 704 days respectively. Conclusions Allo-HSCT is currently the optimal treatment for T315I mutation of CML. And umbilical cord blood is an ideal donor for those patients without HLA-matched sibling donor.