采用含氟达拉滨的增强预处理异基因造血干细胞移植治疗22例重型再生障碍性贫血患者的临床研究  

Fludarabine-based increased-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia

作　　者：孙璨[1] 林遐[1] 黄宇贤[1] 宋朝阳[1] 陶媛[1] 涂三芳[1] 方钧庸 陈土珍[1] 孙彩霞[1] 吴秉毅[1] 

机构地区：[1]南方医科大学珠江医院血液科,广州510282

出　　处：《中华血液学杂志》2014年第3期221-224,共4页Chinese Journal of Hematology

摘　　要：目的观察FBcA（氟达拉滨＋白消安＋环磷酰胺＋ATG）预处理方案对接受异基因造血干细胞移植（allo-HSCT）治疗重型再生障碍性贫血（SAA）患者的供者造血干细胞持续植入的影响。方法2000年1月至2011年6月，接受allo-HSCT的22例SAA患者纳入研究，男12例、女10例，中位年龄21（5～52）岁。外周血造血干细胞移植9例，外周血与骨髓造血干细胞共移植13例；HLA全相合亲缘供者14例，HLA不全相合亲缘供者8例。预处理方案：氟达拉滨30mg·m^-2·d^-1×5d，白消安3mg／kgx2d，环磷酰胺60mg·kg^-1·d^-1×2d，兔ATG2．5mg·kg^-1·d^-1 x5d。采用环孢素＋短程甲氨蝶呤方案预防移植物抗宿主病（GVHD）。于移植后1、3、6、12、24个月通过短串联重复序列（STR）一PCR法观察患者异基因干细胞植入。分析患者长期生存及移植并发症情况。结果22例SAA患者中性粒细胞植入与血小板植入的中位时间分别为15（11-22）、16（12-27）d。22例患者中2例（9．1％）发生I～Ⅲ度急性GVHD，3例（15．8％）发生慢性局限型GVHD。中位随访24（1～141）个月，移植相关死亡3例（巨细胞病毒肺炎、急性GVHD、重症肺感染各1例），19例患者无病生存，中位生存时间为24．0（0．5～140．5）个月。存活的19例患者在allo-HSCT后不同时间点STR-PCR检测结果均为完全供者嵌合体。结论在SAA患者allo-HSCT中，采用免疫抑制较强的FBCA方案进行预处理可获得供者造血干细胞稳定持续植人。Objective To observe the effects of increased-intensity conditioning regimen with FBCA （Fludarabine, Busulfan, Cyclophosphamide, and Antithymocyte globublin） for allogeneic hematopoietic stem cell transplantation （allo-HSCT） in acquired severe aplastic anemia （SAA）. Methods From January 2000 to June 2011, twenty-two patients （male 12, female 10）with SAA underwent allo-HSCT with FBCA conditioning regimen which consisted of fludarabine （30 rag. m-2. d^-1× 5 d）, busulfan （3 mg/kgx2 d）, cyclophosphamide （60 mg.kg^-1.d^-1×2 d） and ATG （2.5 mg.kg-1 .d^-1×5 d）. GVHD prophylaxis was performed by cyclosporine and short-term course methotrexate. Nine patients received mobilized peripheral blood stem cells transplantation and 13 patients underwent mobilized peripheral blood combined with bone marrow stem cells. Fourteen cases were human leukocyte antigen （HLA）- matched related donors, while the other 8 cases were HLA-haploidentical transplantation. Engraftment was documented by short tandem repeats with polymerase chain reaction （STR-PCR） on approximately day ＋ 30, ＋ 90, ＋ 180, ＋ 1 year and ＋ 2 year, respectively. Long-term survival and transplantation-related complications were analyzed. Results All patients obtained prompt and sustained hematopoietic reconstitution. Median time for neutrophil and PLT engraftment was 15 （range： 11-22） days and 16 （range： 12-27） days, respectively. All patients were full donor chimerism identified by STR-PCR. 2 of the total 22 cases （9,1%） had grade I - llI acute GVHD and 3 （15.8%） was chronic GVHD. Three patients （ 13.6% ） died of transplantation related mortality and the other 19 cases were disease-free survival with a median time of 24 （range： 0.5- 140.5） months. The causes of death were cytomegalovirus pneumonia （n=l）, acute GVHD （n=l） and severe pulmonary infection （n=1）. Conclusion Increased- intensity of FBCA conditioning regimen could favor donor stem cell sustained engraftment for allo-HS

关 键 词：贫血 再生障碍性 预处理 造血干细胞移植 

分 类 号：R556.5[医药卫生—血液循环系统疾病]