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霉酚酸酯预防疗程对单倍体相合造血干细胞移植急性移植物抗宿主病的影响

Impact of mycophenolate mofetil prophylaxis duration on acute graft-versus-host disease after haploidentical stem cell transplantation

摘要:

目的 分析霉酚酸酯(MMF)预防疗程对于“北京方案”单倍体相合造血干细胞移植(haplo-HSCT)后急性移植物抗宿主病(GVHD)的影响.方法 回顾性分析2016年9月至2017年3月在北京大学血液病研究所接受haplo-HSCT的237例标危成人(≥14岁)血液肿瘤患者,男140例(59.1%),女97例(40.9%),中位年龄30(14~60)岁.根据MMF疗程分为长疗程组(MMF 500 mg/d口服,-9d开始,+30 d减半,+45 +60 d停药,合并CMV血症、EBV血症或迟发出血性膀胱炎者提前停用)和短疗程组(MMF 500 mg/d口服,-9 d开始,中性粒细胞植活后停药).结果 长疗程组(102例)、短疗程组(135例)MMF中位用药时间分别为27(7~71)、15(9~24)d.两组患者在性别、年龄、疾病类型、HLA不合位点、供受者关系、供受者血型、供者性别、供者年龄方面差异均无统计学意义.长疗程组、短疗程组Ⅱ~Ⅳ度急性GVHD发生率分别为31.1%、17.6%(P=0.018)、Ⅲ/Ⅳ度急性GVHD发生率分别为7.4%、7.8%(P=0.900).多因素分析未发现MMF预防疗程长短对Ⅱ~Ⅳ度急性GVHD有显著影响.两组CMV血症、EBV血症、出血性膀胱炎发生率及总生存率差异均无统计学意义(P值均>0.05).结论 短疗程MMF预防并未增加“北京方案”haplo-HSCT患者急性GVHD发生率,对总生存亦无显著影响,可能是一种安全可行的方案.

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abstracts:

Objective To investigate the impact of mycophenolate mofetil (MMF) prophylaxis duration on acute graft-versus-host disease (aGVHD) after haploidentical stem cell transplantation (haploHSCT) using ‘Beijing Protocol’.Methods Adult patients (≥14 years) received haplo-HSCT in Peking University Institute of Hematology from Sep,2016 to Mar,2017 were retrospectively reviewed if they fulfilled the criterias:①diagnosed with hematological maligancies;②standard-risk status at haplo-HSCT.A total of 237 patients [including 102 patients with long MMF duration (defined as started on day-9 with 100 mg/d,adjusted to 500 mg/d from day +30 and discontinued on day +45 to +60 or occurrence of CMV/ EBV reactivation or late-onset hemorrhagic cytitis),and 135 patients with short MMF duration (defined as started on day-9 with 500 mg/d and discontinued on the day achieved neutrophil engraftnent)] were reviewed.The incidence of aGVHD,virus infection and overall survival (OS) were compared between the two groups.Results The median durations of MMF prophylaxis of long and short duration groups were 27(7-71) and 15(9-24) days,respectively after haplo-HSCT.There were no differences of baseline characteristics (including sex,patient age,disease,mismatched HLA loci,donor-recipient relation,donorrecipient sex and donor age) between the two groups.The incidences of the grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in long and short duration groups were 31.1% versus 17.6% (P=0.018) and 7.4% verus 7.8% (P=0.900),respectively.The duration of MMF prophylaxis was not found to be associated with grade Ⅱ-Ⅳ aGVHD by the multivariate analysis.There were no significant differences in terms of CMV viremia,EBV viremia,hemorrhagic cytitis and OS between the two groups.Conclusion Prophylaxis with short duration MMF in the setting of ‘Beijing protocol’ haplo-SCT was not associated with increased acute GVHD with no impact on OS,which indicated that short duration MMF might be a feasible GVHD prophylaxis regimen.

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作者: 孙于谦 [1] 黄晓军 [1] 许兰平 [1] 张晓辉 [1] 闫晨华 [1] 刘开彦 [1] 王昱 [1]
期刊: 《中华血液学杂志》2018年39卷4期 286-291页 MEDLINEISTICPKUCSCD
栏目名称: 论著
DOI: 10.3760/cma.j.issn.0253-2727.2018.04.005
发布时间: 2018-05-17
基金项目:
国家自然科学基金创新群体基金 国家自然科学基金 北京市自然科学基金(7164303)Innovative Research Groups of the National Natural Science Foundation of China National Natural Science Foundation of China Beijing Natural Science Foundation
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