非清髓性异基因造血干细胞移植治疗高龄白血病

Non-myeloablative allogeneic hematopoietic stem cells transplantation for the treatment of elderly patients with acute leukemia

背景:非清髓异基因造血干细胞移植减轻了预处理强度,减少了移植相关的死亡。目的:分析非清髓性异基因造血干细胞移植治疗老年急性白血病的疗效及其安全性。方法:71岁急性单核细胞白血病M5b患者1例,行非清髓性异基因造血干细胞移植。供者为患者同胞弟弟,60岁,HLA5个位点相合,ABO血型相同。预处理用药包括采用氟达拉滨、塞替派、环磷酰胺和马利兰针剂。移植物抗宿主病预防用抗胸腺球蛋白、巴利昔单抗、环孢素A、麦考酚酯肠溶片及丙种球蛋白,移植后并发症防治和支持治疗:更昔洛韦防治巨细胞病毒感染、前列腺素E1、丹参、肝素及熊去氧胆酸防治肝静脉闭塞症,预处理后外周血中性粒细胞低于0.5×109L-1时开始予粒细胞集落刺激因子5μg/(kg?d)促进造血重建。必要时输注辐照的浓缩红细胞和血小板,供者采用粒细胞集落刺激因子,连用7d,第6,7天采集外周血造血干细胞,当天输注给患者。结果与结论:移植后28d完成造血重建。移植后50d,行STR检测结果显示供受者100%一致。移植后+20～30d陆续出现"出血性膀胱炎"、"败血症(洋葱伯克霍尔德菌胞菌)",移植后2个月出现黄疸、肝功能损害,诊断"急性移植物抗宿主病Ⅲ度(肝脏,3级)",经过抗感染、保肝、调整免疫抑制药物治疗后病情缓解。结果表明采用以氟达拉滨为基础的非清髓性外周血造血干细胞移植治疗有多种合并症老年急性白血病是一种有效安全的方法。

BACKGROUND：Non-myeloablative allogeneic hematopoietic stem cells transplantation can reduce the intensity of conditioning regimen,and decrease the transplantation related mortality rate.OBJECTIVE：To analyze the efficacy and safety of non-myeloablative allogeneic hematopoietic stem cells transplantation for the treatment of elderly patients with acute leukemia.METHODS：A 71-year-old female patient with acute mononuclear cell leukemia M5b underwent the non-myeloablative allogeneic hematopoietic stem cells transplantation.The donor was the younger brother of the patient who was 60 years old,ABO blood type was the same and the HLA loci were mismatched.The conditioning regimen contained fludarabine,thiotepa,cyclophosphamide and Myleran,human anti-thymocyte globulin（ATG）,basiliximab,cyclosporine,mycophenolate mofetil and gamma globulin were used for graft-versus-host disease（GVHD） prophylaxis.The prophylaxis and support therapy of complication after transplantation consisted of Ganciclovir for cytomegalovirus infection,prostaglandin E1,salvia Miltiorrhiza;Heparin and ursodeoxycholic acid for veno-occlusive disease;Granulocyte colony-stimulating factor（G-CSF） 5 μg/kg per day was used when the absolute neutrophil count decreased to 0.5×10^9 /L.Red cells and platelet were infused if necessary.Peripheral blood stem cells（PBSC） of the donor were mobilized with G-CSF for 7 successive days.PBSC were collected and infused to the patient at the 6th and 7th days.RESULTS AND CONCLUSION：Hemopoiesis and immunology reconstruction was completed at the 28th day after transplantation.Results of short tandem repeat（STR） detection shows that the DNA from the donor was the same as the patient at the 50th day after transplantation.The patient suffered from hemorrhagic cystitis and sepsis（Burkholderiacepacia） after transplantation for 20-30 days.Two months later,the patient presented with jaundice and hepatic impairment and she was diagnosed as having acute GVHD（liver,grade 3）.These were controlled with antibiotics and adjusting the regime of immunosuppressive drugs.These findings indicate that non-myeloablative allogeneic hematopoietic stem cells transplantation based on a pretreatment regime containing fludarabine is safe and effective for elderly acute leukemia patients with a variety of complications.