单倍体造血干细胞移植治疗阵发性睡眠性血红蛋白尿症的临床疗效(附1例报告)

Haplo-hematopoietic stem cell transplantation in treatment of paroxysmal nocturnal hemoglobinuria: a case report

目的观察单倍体造血干细胞移植治疗阵发性睡眠性血红蛋白尿症（PNH）的疗效。方法 1例男性43岁PNH患者,行单倍体造血干细胞移植。预处理方案为非清髓的氟达拉滨/环磷酰胺＋抗人T细胞兔免疫球蛋白方案;移植物抗宿主病（GVHD）预防采用环孢素A＋吗替麦考酚酯＋短程甲氨蝶呤方案;肝静脉阻塞病预防采用前列地尔、复方丹参注射液;单倍体造血干细胞供者为其子,患者移植单个核细胞6.51×108/kg,CD34＋细胞4.62×106/kg。移植后检测血常规、肝功能,采用糖水试验、Ham＇s试验观察溶血情况,用流式细胞术监测外周血细胞表面的CD55、CD59及嗜水气单胞菌溶素变异体（FLAER）,抽取骨髓液进行骨髓细胞学及染色体检查。结果患者移植后第15天中性粒细胞〉0.5×109/L;移植后第19天血小板〉20×109/L;移植后第35天糖水试验、Ham＇s试验均转阴,CD55、CD59、ELAER检测结果均正常。随访406 d,患者血常规、骨髓象检查正常,未发生急性GVHD,有慢性皮肤GVHD（局限性）。结论本例PNH患者经单倍体造血干细胞移植治疗后造血功能稳定重建。

Objective To observe the effect of human leukocyte antigen（ HLA） haplo-hematopoietic stem cell transplantation in treatment of patient with paroxysmal nocturnal hemoglobinuria（ PNH）. Methods A 43-year-old male patient with PNH received haploidentical hematopoietic stem cell transplantation. The conditioning regimen was Fludarabine/cyclophosphamide（ Flu/Cy） ＋ anti-human T lymphocyte rabbit immunoglobulin（ ATG-fresen）. Prophylaxis of GVHD was performed with cyclosporine（ CsA）,mycophenolate mofetil（ MMF） and short-term methotrexate（ MTX）. Alprostadil and Fufang Danshen injection was use to prevent hepatic veno-occlusive disease. The patient received 6. 51 × 108 mononucleated cells / kg and 4. 62 × 106CD34＋cells / kg. The blood routine and liver function after transplantation were detected,and the hemolysis was observe by using sucrose hemolysis test and Ham ＇s test. Using flow cytometry to monitor CD55 and CD59 on the surface of peripheral blood cells as well as FLAER loss rate. The bone marrow liquid was extracted to do bone marrow cytology and chromosome examination. Results On day 15 and 19 after transplantation,the neutrophils reached 0. 5 ×109/ L and the platelets reached 20 × 109/ L. Ham test and sucrose hemolysis test were negative,and CD55,CD59,FLAER were normal on day 35 after transplantation. The patient had no acute GVHD,but limited chronic skin GVHD developed. At the last follow-up of 406 days,the patient showed normal hemogram and myelogram. Conclusion Haploidentical hematopoietic stem cell transplantation is successful and safe in treatment of PNH,which indicats persistent hematopoietic reconstitution.