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仅使用药物预防移植物抗宿主病的未处理的HLA 2-3抗原错配(单倍体相合)骨髓移植。

Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis.

作者信息

Ogawa Hiroyasu, Ikegame Kazuhiro, Kaida Katsuji, Yoshihara Satoshi, Fujioka Tatsuya, Taniguchi Yuki, Tamaki Hiroya, Inoue Takayuki, Hasei Hitomi, Iiboshi Yasuhiko, Tazuke Yuko, Kawakami Manabu, Kim Eui Ho, Soma Toshihiro, Inoue Takehiro, Kawase Ichiro

机构信息

Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.

出版信息

Exp Hematol. 2008 Jan;36(1):1-8. doi: 10.1016/j.exphem.2007.08.013. Epub 2007 Oct 17.

Abstract

OBJECTIVE

The incidence of severe graft-vs-host disease (GVHD) in unmanipulated human leukocyte antigen (HLA) 2-3 antigen-mismatched bone marrow transplantation (BMT) using cyclosporine and methotrexate as GVHD prophylaxis is 80% to 90%. We investigated whether pharmacological GVHD prophylaxis consisting of four drugs, including a steroid, effectively suppressed GVHD in this transplantation setting.

MATERIALS AND METHODS

Thirty patients who had hematologic malignancies at an advanced stage or with poor prognosis underwent allogeneic BMT using a myeloablative preconditioning regimen consisting of cyclophosphamide (60 mg/kg x 2), total body irradiation (8-10 Gy), and fludarabine (30 mg/m(2) x 4) with or without cytosine arabinoside (2 g/m(2) x 4), and GVHD prophylaxis consisting of a combination of tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisone (2 mg/kg). Early therapeutic intervention for GVH reaction or grade I GVHD was performed, and steroid was slowly tapered.

RESULTS

All patients achieved donor-type engraftment. Neutrophil (>0.5 x 10(9)/L) and platelet (>20 x 10(9)/L) engraftment was achieved on day 13 and on day 30, respectively. Seventeen patients (56.7%) had no GVHD. Eleven patients (36.7%) developed grade II-III acute GVHD. Seven patients (23.3%) died of transplant-related toxicity, including fungal or viral infections and thrombotic microangiopathy, and four patients died of disease progression. Estimated relapse rate at 3 years was only 20.9%. The probability of survival at 3 years was 49.9%.

CONCLUSIONS

These data suggest that, in unmanipulated HLA-haploidentical allogeneic BMT, this GVHD prophylactic regimen, which includes methylprednisolone 2 mg/kg, and early therapeutic intervention for GVH reaction suppress the incidence of severe GVHD to an acceptable level, while preserving the graft-vs-leukemia effect.

摘要

目的

在使用环孢素和甲氨蝶呤预防移植物抗宿主病(GVHD)的未处理的人类白细胞抗原(HLA)2-3抗原错配的骨髓移植(BMT)中,严重GVHD的发生率为80%至90%。我们研究了由四种药物(包括一种类固醇)组成的药物性GVHD预防方案在这种移植情况下是否能有效抑制GVHD。

材料与方法

30例处于晚期或预后不良的血液系统恶性肿瘤患者接受了异基因BMT,采用由环磷酰胺(60mg/kg×2)、全身照射(8-10Gy)和氟达拉滨(30mg/m²×4)组成的清髓预处理方案,可加或不加阿糖胞苷(2g/m²×4),并采用他克莫司、甲氨蝶呤、霉酚酸酯和甲泼尼龙(2mg/kg)联合预防GVHD。对GVH反应或I级GVHD进行早期治疗干预,并缓慢减少类固醇用量。

结果

所有患者均实现供者型植入。中性粒细胞(>0.5×10⁹/L)和血小板(>20×10⁹/L)分别在第13天和第30天实现植入。17例患者(56.7%)未发生GVHD。11例患者(36.7%)发生II-III级急性GVHD。7例患者(23.3%)死于移植相关毒性,包括真菌或病毒感染以及血栓性微血管病,4例患者死于疾病进展。3年时的估计复发率仅为20.9%。3年时的生存概率为49.9%。

结论

这些数据表明,在未处理的HLA单倍体相合异基因BMT中,这种包括2mg/kg甲泼尼龙的GVHD预防方案以及对GVH反应的早期治疗干预可将严重GVHD的发生率抑制到可接受水平,同时保留移植物抗白血病效应。

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