非血缘异基因造血干细胞移植治疗白血病21例临床观察

摘要

目的：观察非血缘异基因造血干细胞移植治疗白血病的临床疗效及并发症。方法回顾性分析21例非血缘异基因造血干细胞移植的恶性血液病患者临床资料,其中19例为外周血造血干细胞移植,1例为骨髓移植,1例为脐血移植。HLA 全相合8例,HLA 不全相合13例。回输单个核细胞(MNC)中位数9.078×108/kg,CD34+细胞中位数4.62×106/kg。10例患者采用 BuCy 方案预处理,9例采用改良的 BuCy2方案预处理,1例采用非清髓的 BuCy+氟达拉滨的方案,1例采用 TBI+VP-16+CTX+meCCNU 预处理。预防移植物抗宿主病方案,其中20例采用短程甲氨蝶呤+环孢素 A+霉酚酸酯+抗胸腺细胞免疫球蛋白的四联方案,1例脐血移植患者采用短程甲氨蝶呤+环孢素 A +抗胸腺细胞免疫球蛋白。术后观察受者的造血重建、并发症以及预后情况。采用低剂量肝素+前列腺素 E1+丹参注射液预防肝静脉闭塞病(VOD)。结果除 1例患者于空髓期死于颅内出血,其余20例患者均获造血重建。高剂量组MNC 及 CD34+细胞较低剂量组中位重建时间平均缩短1 d。预处理中出现高热、寒战、胃肠道副反应、肝脏损伤及口腔黏膜炎等副反应,均给予对症处理后好转。HLA 不合者较 HLA 全相合者移植后移植物抗宿主病(GVHD)发生率高,差异有统计学意义。9例患者出现 aGVHD(Ⅰ度 3例,Ⅱ度4例,Ⅲ度2例)；9例出现 cGVHD,表现为皮肤及肝脏受损,经有效治疗后好转。术后100 d 内18例受者出现细菌或真菌感染,以上呼吸道感染为主,7例发生巨细胞病毒感染,2例出现 EB 病毒血症,1例出现尿 BK 病毒感染。1例患者因 VOD 死亡,其余患者均未发生 VOD。5例发生Ⅱ级至Ⅲ级出血性膀胱炎,经治疗后均好转。受者总的中位生存时间为24月(136 d~9年),1年及3年总生存率分别为85.2%和63.9%,无病生存率分别为81.0%和23.8%,无复发生存率为71.4%和14.3%。结论非血缘异基因造血干细胞移植是治疗白血病的有效方法；BuCy 及改良 BuCy2的预处理方案均安全有效,毒性反应可逆、可耐受；高剂量 MNC 及 CD34+细胞数组造血重建时间较低剂量组缩短；HLA 不全相合者移植后 GVHD 发生率较 HLA 全相合者增高；低剂量肝素+前列腺素 E1+丹参注射液可有效预防 VOD。%non-myeloablative BuCy+fludarabine conditioning regimen,and another one was treated with TBI+VP-1 6 +CTX+CCNU conditioning regimen.Only one case received short-term MTX,cyclosporin A and ATG regimen for prevention of graft-versus-host disease (GVHD).The GVHD prevention regimens of the other patients were based on short-term MTX,cyclosporin A,ATG and mycophenolate mofetil regimen.The hematopoietic reconstitution, complications and prognosis were observed.Results One patient died of intracranial hemorrhage,and hematopoi-etic reconstitution was achieved in the other 20 patients.The median time for hematopoietic reconstitution shortened by one day in large-dose group compared with that in low-dose group.Adverse reactions included high fever, shivering,gastrointestinal tract adverse reaction,liver injury,oral mucositis and other rare side effects.GVHD occurred more frequently in patients with HLA mismatched transplantation.Nine patients with aGVHD and 9 patients with cGVHD recovered after effective treatment.Within 100 days after transplantation,18 patients had bacterial or fungal infection,mainly upper respiratory tract infection;7 patients had cytomegalovirus infection;2 had EB viremia,and one had urinary BK virus infection.Only one patient died of VOD.Hemorrhagic cystitis occurred in 5 patients and improved after treatment.The median survival time was 24 months (ranging from 136 days to 9 years).One-year and 3-year overall survival rates were 85.2% and 63.9%,the disease free survival rates were 81% and 23.8%,recurrence free survival rates were 71.4% and 14.3%,respectively.Conclusion URD-HSCT was an effective method to treat leukemia.Conditioning regimen of BuCy and modified BuCy2 were safe and effective,the adverse reactions were reversible and well tolerated.Hematopoietic reconstitution time shortened in large-dose MNC and CD34 + cell number groups compared with that in low-dose group.The occurrence rate of GVHD with HLA mismatched transplantation was more than that of HLA matched transplantation.Low-dose heparin,prostaglandin E1 and Danshen injection can effectively prevent VOD.