中低剂量全身放疗在非清髓性异基因造血千细胞移植中作用观察

Application of Total Body Radiation with the Middle or Low Dose on Non-myeloablative Allogeneic Stem Cell Transplantation in the Treatment of Relapsed and Refractory Leukemia.

目的观察中低剂量全身放疗加氟达拉宾在非清髓异基因造血干细胞移植（non-myeloablastic hematopoietic stem cell transplantation，NST）对未缓解期难治性白血病患者预处理方案的作用。方法20例未缓解期难治性白血病患者，采用以中低剂量的全身放疗（TBI）加氟达拉宾（FLU）为基础的减低剂量的预处理方案行非清髓异基因造血干细胞移植。结果早期死亡5例，17例造血细胞成功植入，中性粒细胞〉0．5×10^9／L的中位时间为13d（11～17d），血小板〉50×10^9／L的中位时间为19d（11～42d）。外周血T细胞STR-PCR检测16例达到完全供者嵌合，中位时间为14d（7～42d）。急性移植物抗宿主病（GVHD）发生率为8／17，慢性GVHD的发生率为5／13。7例血液学复发，目前无病存活9例，Kaplan-Meier法分析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）％。结论中低剂量全身放疗加FLU为基础的非清髓异基因造血干细胞移植预处理方案，耐受性好，移植相关死亡率低，能够用于治疗难治性白血病。

Objective To evaluated the efficacy of total body radiation with the middle or low dose on non-myeloablative allogeneic stem cell transplantation（NST） in the treatment of relapsed and refractory leukemia, Methods 20 patients with relapsed and refractory leukemia were received total body irradiation（TBI） and fludarabine based NST conditioning regimen, Graft versus host disease （GVHD） prophylaxis program consist of CSA plus mycophenolate mofetil or MTX, or all of them; CD25 or CD52 monoclone antibody and ATG were also used in some of the patients. Results Five patients died within 40days because of graft failure, intracranial hemorrhage and severe infection. There were 17 patients engrafted successfully, the median time to ANC〉0.5×10^9/L was 13 days（range： 11-17days）, and the median date to BPC〉50×10^9/L was 19 days（range： 11-42days）. When detection of STR by PCR was performed, complete donor chimerism was shown in 16 patients with a median date of 14days （range： 7-42 days）, The incidences of acute GVHD and chronic GVHD were 8/17 and 5/13 respectively. There were 7 patients relapsed, and at the time of last follow up 10 patients were still alive and 9 were leukemia free, the overall survival（OS） at 2 year was （35.3±14.2）% with all patients and （52.5±18.6）% with non-lymphocyte leukemia patients. Conclusion TBI and fludarabine based NST could be used in the treatment of refractory leukemia with well tolerance and low transplant related mortality from which patients may be benefit. Patients with non-lymphocyte acute leukemia had better prognosis than that with lymphocyte acute leukemia.