减低剂量预处理的异基因造血干细胞移植治疗难治性白血病20例分析

目的 观察减低剂量预处理的异基因造血干细胞移植(allo-HSCT)对难治性白血病未缓解期的疗效.方法 20例未缓解期难治性白血病患者,采用以氟达拉滨(Flud)联合小到中等剂量的全身照射(TBI)治疗为基础的减低剂量的预处理方案行allo-HSCT.采用环孢素A加霉酚酸酯或短程甲氨蝶呤,或三种药物联合应用预防移植物抗宿主病(GVHD),部分患者还加用了CD52单抗、CD25单抗或抗胸腺细胞球蛋白.结果 17例患者造血细胞成功植入,中性粒细胞＞0.5 × 109 /L的中位时间为13(11～17)d,血小板＞50×109 /L的中位时间为19(11～42)d.外周血T细胞短串联重复序列PCR检测,16例达到完全供者嵌合,中位时间为14(7～42)d.急性GVHD发生率为47.1%(17例中8例),慢性GVHD的发生率为38.5%(13例中5例).移植相关死亡率25.0%(20例中5例),死亡原因主要为植入失败、颅内出血和严重感染.7例血液学复发,目前无病存活9例,Kaplan-Meier法分析全组患者2年总体生存率为(35.3±14.2)%;而其巾急性非淋巴细胞白血病患者2年总体生存率为(52.5±18.6)%.结论 以Flud联合TBI为基础的减低剂量的allo-HSCT预处理方案,耐受性好,移植相关死亡率低,能够用于治疗难治性白血病,并有可能通过降低移植相关死亡率提高总体生存率,急性非淋巴细胞白血病预后优于急性淋巴细胞白血病患者.

Allogeneic hematopoietic stem cell transplantation following reduced intensity conditioning regimen for treatment of refractory leukemia

Objective To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT)following reduced intensity conditioning(RIC)regimen for treatment of refractory leukemia.Methods Twenty patients with refractory leukemia received allo-HSCT following RIC regimen consisting of fludarabine plus small or modcrate dose total body irradiation(TBI).Graft versus host disease(CVHD)prophylaxis was CsA plus myeophenolate mofetil(MMF)or short-term MTx,or these three drags combination;CD25 monoelone antibody(McAb)and ATG were also used in some of the patients.Results Seventeen patients engrafted successfully,the median time for ANC＞0.5×109 /L was 13(11-17)days,and for BPC＞50×109/L 19(12-42)days.Detected by short tandem repeat(STR)-PCR,complete donor chimerism was comfirmed in 16 patients with a median of 14(7-35)days.The incidence of acute and chronic GVHD was 47.1%(8/17)and 38.5%(5/13)respectively.The transplant related mortality(TRM)was 25.0%(5/20),mainly from graft failure,intracranial hemorrhage and severe infection.Up to now,7 patients relapsed and 9 were alive with leukemia free.The overall survival(OS)at 2 year was(35.3±14.2)%for all patients and(52.5±18.6)%for acute non-lymphocytic leukemia(ANLL)patients.Conclusion Allo-HSCT following fludarabine and TBI based RIC regimen can be used for treatment of refractory leukemia with well tolerance and low TRM and there is a better prognosis for ANLL patients than that for acute lymphocytic leukemia patients.