非清髓性造血干细胞移植后移植物抗宿主病的临床观察

目的 观察非清髓性造血干细胞移植（NST）后移植物抗宿主病（GVHD）的发生情况。方法 将18例患者分为3组：A组为6例重型再生障碍性贫血（SAA）成人患者，行无关供者脐血造血干细胞移植；B组为5例SAA患者，行同胞供者骨髓联合外周血造血干细胞移植；C组为7例肿瘤性血液病患者，其中3例行同胞供者骨髓移植，4例行外周血造血干细胞移植。均采用以抗胸腺细胞球蛋白或抗淋巴细胞球蛋白为基础的预处理方案。A组和B组应用环孢素A（CsA）和甲泼尼龙预防GVHD，C组应用CsA和甲氨蝶呤预防GVHD。C组形成混合性嵌合体后行供者淋巴细胞输注（DLI）。结果 A组有4例形成并维持混合性嵌合体状态，1例死于真菌性败血症，1例自动出院。移植后早期，B组有3例供者型嵌合体占94％以上，并在短期内转变并维持完全供者嵌合体状态，获得无病存活，其中1例在移植后8个月发生慢性GVHD；另2例行供者千细胞输注后，1例6个月后死于继发性纵隔淋巴瘤，1例造血功能恢复。C组患者早期均形成混合性嵌合体，获得血液学部分缓解，患者DLI前无急性GVHD发生，1例于2次DLI后死于严重感染，1例失访；另5例分别经过4、3、7、5、4次DLI，全部转为完全供者型嵌合体，并获得血液学完全缓解，4例并发慢性GVHD，2例并发急性GVHD。结论 对于SAA患者，NST的临床效果较好，GVHD的发生率较低；而对于肿瘤性血液病，NST后患者的早期死亡率低，急性GVHD发生率下降，但慢性GVHD和感染的发生率较高。

Clinical study on graft-versus-host disease post non-myeloablative stem cell transplantation for haematologic diseases

Objective To explore clinical features of graft-versus-host disease (GVHD) after allogeneic non-myeloablative stem cell transplantation (NST) for haematologic diseases.Methods Eighteen patients were divided into three groups. Group A: Six severe aplastic anemia (SAA) adult patients underwent unrelated umbilical cord blood transplantation (UCBT). Group B: Combined transplantation of G-CSF primed allogeneic bone marrow and peripheral blood stem cells (PBSCs) was performed for 5 SAA patients. Group C: Seven malignant haematologic patients underwent transplantation of bone marrow cells for 3 patients or PBSCs for 4 patients. The protocol consisted of nonmyeloablative conditioning regimens based on anti-themocyte globulin (ATG) or anti-T-lymphocyte globulin (ALG). GVHD prophylaxis consisted of cyclosprine (CSA) and methylprednisolone (MP) for groups A and B, and methotrexate and CSA for group C. Mixed chimerism (MC) patients in group C were subjected to donor lymphocyte infusion (DLI).Results Four patients in group A achieved and sustained MC status, among them, one patient died of fungal septemia and one patient left hospital voluntarily. Three patients in group B achieved short period MC with donor chimerism more than 94 % at early stage post transplantation and converted into full donor chimerism (FDC) with long-term disease-free survival (DFS) and one patient developed chronic GVHD (cGVHD) 8 month post- trasplantation . Another two patients receiving donor stem cell infusion (DSI), one died of secondary mediastina lymphoma after 6 months and one patient recovered haematopoiesis. All patients achieved MC with haematologic partial remission (PR), and did not complicated acute GVHD (aGVHD) prior to DLI. Two cases died of severe infection and lost follow-up respectively. Another 5 patients gradually converted into FDC and achieved haematologic complete remission after 4, 3, 7, 5 and 4 DLIs, but they developed cGVHD (n=4), aGVHD (n=2) and myelosurppression (n=2).Conclusion The treatment of NST for SAA patients achieved better clinical effect with lower incidence of GVHD, and characterized by lower incidence of aGVHD and early mortality and higher incidence of cGVHD and infection for malignant haematologic diseases.