摘要
目的:观察急性髓性白血病经混合造血干细胞移植后,应用供者淋巴细胞输注+白细胞介素2治疗的效果,并与移植后未经特殊治疗的效果进行比较。方法:①选取2000-01/2004-07解放军兰州军区兰州总医院全军血液病中心收治的19例急性髓性白血病患者,实验经医院伦理委员会批准,患者均知情同意。随机数字表法分为两组:观察组8例,年龄17～40岁,M2a 4例,M4 1例,M5a 3例;对照组11例,年龄19～39岁,M2a 2例,M3a 2例,M4 3例,M5a 4例。②两组患者采用化疗联合重组人粒细胞集落刺激因子的方法动员自体外周血造血干细胞,采集后液氮中保存5d备用。③术前采用直线加速器对患者全身及肺部照射,预处理完毕后实施混合造血干细胞移植。首先回输自体单个核细胞中位数为4×108/kg,CD34+细胞中位数为6.2×106/kg,粒-巨噬祖细胞集落形成单位中位数为5.8×104/kg。间隔1～6h后,采集人类白细胞抗原半相合异体骨髓,按回输自体单个核细胞数的1/6～1/10输注给患者。④两组患者移植期间均住无菌层流病房,给予相应并发症的防治及支持治疗。在粒细胞降至0时注射重组人粒细胞集落刺激因子150μg/12h,促进造血恢复。观察组给予供者淋巴细胞输注+白细胞介素2治疗,每次采集的供者淋巴细胞中,CD3+淋巴细胞中位数为1.43×108/kg,CD4+细胞中位数为0.97×108/kg,CD8+细胞中位数为0.41×108/kg,中位治疗次数4(1～7)次,回输后即开始应用100wu/d重组人白细胞介素2,共10d。对照组混合造血干细胞移植后未给予特殊治疗。结果:19例急性髓性白血病患者均进入结果分析。①造血恢复:两组患者均获得造血重建,术后4～9d粒细胞均降至0,12～17d粒细胞达0.5×109L-1,16～21d白细胞达4.0×108 L-1,19～23 d血小板达20×108 L-1。16～21 d骨髓检查示恢复期骨髓象。②术后并发症:两组患者不同程度地出现口腔溃疡,随着造血恢复,7～10d溃疡消失。观察组1例患者出现出血性膀胱炎,两组各2例患者出现发热。无肝静脉闭塞病和移植物抗宿主病发生。③嵌合体形成:观察组中1例M4患者形成嵌合体,对照组中2例M4患者与1例M5患者形成嵌合体,嵌合体持续存在3～12个月。④供者淋巴细胞输注+白细胞介素2疗效:观察组中有1例M2a患者在接受2次特殊治疗后7个月复发死亡;1例M2a患者接受2次特殊治疗后1年出现骨髓增生异常综合征,脑出血死亡,1例M5a患者应用特殊治疗1次后出现不明原因高热、抽搐,死于癫痫持续状态,其余5例患者随访2年均健康存活,长期生存率为62.5%(5/8)。对照组有2例M2a患者、2例M4患者、1例M5患者于移植后1～7个月复发死亡,1例M3患者于移植后25d死于脑出血,其余2例M3患者、2例M4患者、1例M5患者随访2年均健康存活,长期生存率为45.4%(5/11)。结论:混合造血干细胞移植后应用供者淋巴细胞输注+白细胞介素2治疗,急性髓性白血病患者均获得造血重建且无移植物抗宿主病发生,其长期生存率有效提高。
AIM： To investigate the curative effect of donor lymphocyte infusion （DLI） and intedeukin-2 ilL-2） after mixed hematopoietic stem call transplantation （HSCT） in acute myelogenous leukemia （AML）, and compare with that of no using DLI＋IL-2 after mixed HSCT. METHODS： ①Nineteen patients who were diagnosed as AML and treated at Department of Hematology, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from January 2000 to July 2004. With the approval of Ethics Committee of Lanzhou General Hospital, all the patients were informed of and agreed with the treatment scheme. They were divided randomly into two groups： Eight cases in observation group aged 17-40 years, including 4 cases of M2a, 1 case of M4 and 3 cases of M5a; Eleven cases in control group aged 19-39 years, including 2 cases of M2a, 2 cases of M3a, 3 cases of M4 and 4 cases of M5a. ②The peripheral blood stem cells in patients of two groups were mobilized using chemotherapy combined recombinant human granulocyte colony stimulating factor （rhG-CSF）, then harvested and froze in fluidity nitrogen for 5 days. ③Before transplantation, the patients were treated with lung and total body irradiations using a linear accelerator, followed by mixed HSCT. Mean count of autologous mononuclear call （MNC） was 4×10^8/kg, CD34^＋ call was 6.2×10^6/kg and granulocyte-macrophage colony-forming unit was 5.8×10^4/kg. And 1-6 hours later, allogeneic bone marrow cells of human leucocyte antigen-haploidentical were harvested and infused to patients according to 1/6-1/10 of autologous MNCs.④During treatment, all the patients were injected with rhG-CSF 150 μg/12 h when their granulocytes fell to 0, in order to recover hematopoietic function. The patients of observation group received treatment of DLI＋IL-2. Mean counts of CD3^＋ lymphocyte in donor lymphocyte were 1.43×10^8/kg, CD4^＋ calls were 0.97×10^8/kg, CD8^＋ calls were 0.41×10^8/kg. Patients received this treatment from 1 to 7 times, mean 4 times. After infusion, the patients of observation group were treated with recombinant human IL-2, 100 wu/d for 10 days. The patients of control group were not received this treatment after mixed HSCT. RESULTS： All the 19 cases of AML entered the result analysis. ①Hematopoietic recovery： Two groups of patients received hematopoietic recovery. The granulocytes fell to 0 in 4-9 days after transplantation and increased to 0.5×10^9 L^-1 in 12-17 days. White blood calls increased to 4.0×10^8 L^-1 in 16-21 days and the platelet increased to 20×10^8 L^-1 in 19-23 days. Bone marrow detection showed recovery during 16-21 days.②Complication： Two groups of patients appeared oral ulcer in different extents and disappeared in 7-10 days following hematopoietic recovery. One case of patient in observation group appeared hemorrhagic cystitis and 4 cases of patients in two groups appeared fever. There were no hepatic venous occlusive disease and graft-versus-host disease.③Chimera： In observation group, 1 case of M4 formed chimera after mixed HSCT; In control group, 2 cases of M4 and 1 case of M5 formed chimera, which was observed for 3-12 months, ④The curative effect of DLI＋IL-2：1 case of M2a in observation group, treated with 2 special treatments after transplantation, died of relapse in 7 months. 1 other case of M2a had myelodysplastic syndromes after 1 year of special treatment, and died of brain blooding. Another case of M5a was died by no reason, appearing high fever and spasm. The other 5 patients were alive without disease during 2 years of follow-ups. The disease free survival （DFS） was 62.5% （5/8）. In control group, 2 cases of M2a, 2 of M4, 1 of M5 all died 1-7 months after HSCT. 1 case of M3 died of brain blooding 25 days after HSCT. The other patients including 2 cases of M3, 2 of M4 and 1 of M5 subsisted during 2 years of follow-ups, the DFS was 45.5% （5/11 ）. CONCLUSION： Using a treatment with DLI＋IL-2 after mixed HSCT, the AML patients can obtain hematoboietic recovery and increase DFS efficiently. No graft-versus-host disease appears.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第24期4777-4780,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
