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1、精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询非清髓性异基因造血干细胞移植治疗恶性血液病 26例作者：苏丽萍，许莲蓉，姜波，叶芳，朱秋娟，鹿育晋，崔月娥，朱镭，张丽，马香兰【摘要】 为研究非清髓性异基因造血干细胞移植（non-myeloablative allogeneic stem cell transplantation，allo-NST）治疗恶性血液病的疗效及相关技术，选择 26 例恶性血液病患者作为研究对象（急性白血病 10 例，慢性髓性白血病 14 例，多发性骨髓瘤 2 例） ，其中 14 例采用 FAC（fludarabin+ATG+Cy)预处理，12 例采用 MAC（mel
2、falan/maleran+ATG+Cy)预处理；用 G-CSF 600 g/d 或 G-CSF 300 g/d+GM-CSF 300g/d 进行外周血干细胞动员，于第 5 天开始用 Cobe Spectra 血细胞分离机连续采集 2-3 次；用环孢菌素 A 联合短程甲氨蝶呤预防 GVHD；移植后第 4 周开始供体淋巴细胞输注，首剂 1107/kg，之后依据临床反应及嵌合体形成情况，每 4 周 1 次，剂量逐级递增；微卫星短串联重复序列（STR）分析、Bcr/Abl 融合基因、Ph 染色体、HLA 位点分析、性染色体及ABO 血型等为植活检测指标。结果显示： 植入率 84.62%，aGVHD
3、发生率 11.54%，cGVHD 发生率 23.07%；感染和出血等毒副反应发生率精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询低、反应轻。结论：非清髓性异基因造血干细胞移植治疗恶性血液病疗效确切，毒副作用小，但相关技术，如适应症的选择、预处理方案、移植过程中的免疫治疗等需要进一步深入研究。 【关键词】 造血干细胞移植；非清髓性异基因造血干细胞移植； 恶性血液病Nonmyeloablative Allogeneic Hematopoietic Stem cell Transplantation in 26 Cases of Hematological MalignanciesAbstra
4、ct The purpose of this study was to investigate the efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and its related technologies in hematological malignancies. 26 patients with hematological malignancies (acute leukemia 10，chronic myeloid leukemia 14，multiple myeloma 2)
5、 received allo-NST following conditioning regimens with fludarabin/cyclophosphamide/ATG in 14 cases or busulfan or melphalan/ cyclophosphamide/ATG in 12 cases prior to infusion of 2 or 3 collections of G-精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询CSF(600 g/d) or G-CSF(300 g/d) plus GM-CSF(300 g/d) mobilized blood st
6、em cell on the fifth day. A combination of cyclosporine A (CsA) and methotrexate(MTX) was administered for GVHD prophylaxis. Patients were eligible for donor lymphocyte infusion (DLI) (or donor stem cell infusion (DSI) )given in graded increments according to the chimeric formation and clinical feat
7、ure. Generally，the dose of the first infusion was 1l07/kg in 4th week post-transplantation. The engraftment analyses included the detection of microsatellite short tandem repeats (STRs)，bcr/abl fusion gene，Philadelphia chromosome，HLA-locus analysis，sex chromosome and ABO blood type or blood subtype.
8、 The results showed that out of 26 patients，22 (84.62%) were engrafted，18/22 were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 (11.54%)，while chronic GVHD was diagnosed in 6 out of 26 (23.07%) patients. The incidence and degree of infection and hemorrhage were low and slight. It
9、 is concluded that NST is a safe and effective therapy for hematological malignancies，whereas related technologies such as adaptation selected，conditioning regimen and transplantation immunotherapy should be studied further.精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询Key words hematopoietic stem cell transplantation;
10、 nonmyeloablative allogeneic hematopotetic stem cell transplantation; hematological malignancyAs conventional allogeneic hematopoietic stem cell transplantation (HSCT) for patients with hematological malignancies both eradicates the patients underlying diseases and suppresses their immune responses，
11、they do not reject the subsequent allografts. The allografts serve to “rescue” patients from the marrow lethal effects of the conditioning regimens. Consequently，the conditioning therapy intensity would be limited only by toxicities to non-marrow organs， such as gut，lung，kidney，heart，and liver. Thes
12、e toxicities have restric-ted HSCT to younger，medically fit patients，with treatment administered in specialized hospital wards. Almost no allogeneic HSCT have been carried out in patients 60 years old，and in only a few patients older than 50 years. Since median ages at diagnoses of patients with acu
13、te myelocytic 精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询leukemias (AML)，chronic myelocytic leukemias(CML)，chronic lymphocytic leukemias(CLL)，non-Hodgkin lymphomas (NHL)，and multiple myelomas (MM) range from 65-70 years，so that conventional allogeneic HSCT benefit only a minority of patients with candidate disease.N
14、onmyeloablative allogeneic stem cell transplantation (NST) was first described and applied in 1997 by Giralt and colleages1-3. Because of their low toxicity，nonmyeloablative allogeneic stem cell transplantation shows a promise to reduce the morbidity and mortality associated with conventional high-d
15、ose chemoradiotherapy and allows allogeneic transplants in elderly or medically infirm patients who are not eligible for conventional myeloablative HSCT. So it has been increasingly explored as a safe alternative to conventional high-dose transplantation regimens.We analyzed NST with its adaptation，
16、conditioning regimen，engraftment，immunotherapy and complications，such 精品文档欢迎来主页查询更多精品文档,欢迎来我主页查询as GVHD，in details in 26 patients with hematological malignancies who underwent NST from September 1998 to September 2002.Materials and MethodsPatient characteristicsDuring the period from September 1998 to September 2002，26 patients were diagnosed as hematological malignancies and treated with NST in our department. Of these patients，male and female were 15 and
