非血缘异基因造血干细胞移植治疗白血病21例临床观察
Clinical observation of 21 cases of unrelated donor hematopoietic stem cell transplantation for leukemia

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9.078×10？？8/kg，CD34+细胞中位数4.62×10？？6/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1d。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100d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(136d～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。
ABSTRACT: Objective To study the therapeutic effectiveness and associated complications of unrelated allogeneic hematopoietic stem cell transplantation (URD-HSCT) for leukemia. Methods Twenty-one patients with malignant hematological diseases received URD-HSCT. There were 19 cases of peripheral blood hematopoietic stem cell transplantation, one case of bone marrow transplantation, and one case of umbilical cord blood transplantation. There were 8 cases of HLA matched and 13 cases of HLA mismatched transplantation. The median of infused donor MNC was 9.078×108/kg, and the median of CD34 positive cells was 4.62×106/kg. Ten patients were treated with BuCy conditioning regimen, nine patients with modified BuCy2 conditioning regimen, one with non-myeloablative BuCy+fludarabine conditioning regimen, and another one was treated with TBI+VP-16+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 hematopoietic 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