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儿童急性白血病的 HLA 全相合造血干细胞移植:较高生物效应剂量的全身照射可减少复发

HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI.

作者信息

Willemze A J, Geskus R B, Noordijk E M, Kal H B, Egeler R M, Vossen J M

机构信息

Division of Immunology, Hematology, Oncology and Bone Marrow Transplantation and Autoimmune Diseases, Department of Paediatrics, Leiden University Medical Centre, Albinusdreef 2, 2300 RC Leiden, The Netherlands.

出版信息

Bone Marrow Transplant. 2007 Aug;40(4):319-27. doi: 10.1038/sj.bmt.1705729. Epub 2007 Jun 18.

Abstract

To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.

摘要

为了研究复发、生存情况以及与移植相关的并发症与疾病及预处理相关特征之间的关系,我们评估了132例儿童患者,这些患者在我们中心连续接受了同基因HLA相合的急性白血病异基因造血干细胞移植:首次缓解期的急性淋巴细胞白血病(ALL)患者24例、第二次缓解期的ALL患者53例以及首次缓解期的急性髓系白血病(AML)患者55例。除3例患者外,所有患者的干细胞来源均为骨髓。大多数患者(89%)接受了环磷酰胺和与年龄相关剂量的全身照射(TBI)预处理。最初,移植物抗宿主病(GVHD)预防仅采用长疗程甲氨蝶呤(MTX)(24例),后来采用短疗程MTX和环孢素A(CsA)(102例)。所有患者均在严格的保护性隔离环境中护理,并接受全肠道去污以抑制其潜在致病的肠道微生物群。ALL1、ALL2和AML1患者的5年总生存率分别为63%、53%和74%(中位随访时间:10.6年)。总体移植相关死亡率为6%。急性GVHD的发生率为17%;II-IV级为6%。更高的总生物等效TBI剂量(BED)导致复发频率降低(P = 0.034)并提高了总生存率。发生急性GVHD的AML患者未出现复发(P = 0.02);ALL患者则不然。应在前瞻性研究中评估具有更高BED的分次TBI方案。

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