同胞全相合、无关供体全相合及亲缘间单倍型异基因造血干细胞移植治疗伴有费城染色体急性淋巴细胞白血病:疗效和安全性

Different types of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia:therapeutic efficacy and safety

背景:随着移植方案的优化及移植物抗宿主病治疗药物的出现,使得异基因造血干细胞移植近年来取得了巨大的进步,为越来越多的恶性血液病患者争取了长期生存的机会。目的:比较3种移植方式即同胞全相合、无关供体全相合及亲缘间单倍型异基因造血干细胞移植治疗伴有费城染色体急性淋巴细胞白血病(Ph+ALL)的疗效和安全性。方法:2006年6月至2013年11月间,69例伴有费城染色体急性淋巴细胞白血病患者接受异基因造血干细胞移植。同胞全相合移植23例,无关供体全相合移植24例,亲缘间单倍型移植22例;其中54例为CR1状态,12例为CR2到CR4状态,3例复发状态。获取供者骨髓干细胞或者外周血干细胞用于移植。预处理方案为阿糖胞苷、白消安、环磷酰胺及全身照射等。联合使用环孢素A+短程甲氨蝶呤+吗替麦考酚酯+抗人胸腺细胞球蛋白等预防移植物抗宿主病。结果与结论:(1)68例患者获得造血重建,仅1例单倍型植入失败;(2)患者随访时间中位数为20.4个月,同胞全相合、无关供体全相合及亲缘间单倍型移植的急性移植物抗宿主病发生率分别为30%,33%及45%,慢性移植物抗宿主病发生率22%,29%及36%,各组间急性移植物抗宿主病、慢性移植物抗宿主病发生率比较差异无显著性意义;(3)同胞全相合、无关供体全相合及亲缘间单倍型移植的移植相关死亡率为9%,29%及41%,各组间比较差异有显著性意义(0.01<P<0.05)。复发率为17%,21%及14%,各组间比较差异无显著性意义;(4)同胞全相合、无关供体全相合及亲缘间单倍型移植的3年总体生存率为68%,49%及43%,同胞全相合组与无关供体全相合组、同胞全相合与亲缘单倍型组分别比较,差异有显著性意义(P均<0.05),而无关供体全相合与亲缘间单倍型移植比较差异无显著性意义;(5)54例CR1状态移植患者3年总体生存率为58%;15例于非CR1状态移植患者3年总体生存率为41%;(6)结果表明,同胞全相合移植疗效优于无关供体全相合及单倍型移植;CR1状态下行异基因造血干细胞移植的疗效显著优于CR2以上状态。

BACKGROUND:With the optimization of transplantation scheme and the emergence of graft-versus-host disease(GVHD)therapy drugs,allogeneic hematopoietic stem cell transplantation(allo-HSCT)in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities.OBJECTIVE:To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome(Ph)in acute lymphoblastic leukemia(Ph+ALL).METHODS:A total of69patients with Ph+ALL who received allo-HSCT from June2006to November2013were enrolled,including23cases of sib-matched donor transplantation,24cases of unrelated-matched donor transplantation,and22cases of haploidentical donor transplantation.There were54cases of CR1,13cases of CR2to CR3and3cases of relapse.The bone marrow or/and peripheral blood stem cells were used for transplantation.All patients were subjected to pretreatment consisting of cytarabine,busulfan,cyclophosphamide and total body irradiation.GVHD was prevented by combined use of immunosuppressants including cyclosporine A,short-term methotrexate,mycophenolate mofetil and anti-human thymocyte globulin,etc.