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

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

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〉0.5×10^9／L的中位时间为13（11～17）d，血小板〉50×10^9／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）％；而其中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皿病，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。

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 moderate dose total body irradiation （TBI）. Graft versus host disease （GVHD） prophylaxis was CsA plus mycophenolate mofetil （MMF） or short-term MTX, or these three drugs combination; CD25 monoclone antibody（McAb） and ATG were also used in some of the patients. Results Seventeen patients engrafted successfully, the median time for ANC 〉 0.5 × 10^9/L was 13 （ 11 - 17） days, and for BPC 〉 50 × 10^9/L 19 （ 12 -42） days. Detected by short tandem repeat （ STR）-PCR, complete donor chimerism was conffirmed 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. Conclnsion 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.