Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: Possible role for pre-emptive immunotherapy?

Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: Possible role for pre-emptive immunotherapy?
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DOI:
10.1200/jco.2004.05.198
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发表时间:
2004-05-01
影响因子:
45.3
通讯作者:
Klingebiel, T
Klingebiel, T
中科院分区:
医学1区
文献类型:
--
作者:
Bader, P;Kreyenberg, H;Klingebiel, T

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目的:我们最近报道了急性白血病患儿在异基因干细胞移植后表现出混合嵌合体(MC)增加,复发风险显著增加。本文介绍一项前瞻性多中心研究的结果,以探讨(1)急性淋巴细胞白血病(ALL)的复发是否可以通过嵌合体的系列分析提前确定,和(2)当检测到MC增加时,是否可以通过取消免疫抑制和/或通过低剂量供体淋巴细胞输注来影响结果。结果101例ALL患儿表现为完全嵌合体(CC)或低水平MC(CC/低水平MC),46例MC增高,16例MC降低。MC升高患者的复发率(26/46)显著高于CC/低水平MC患者(8/101)或MC降低患者(0/16; P
Purpose We recently reported that children with acute leukemias who show increasing mixed chimerism (MC) after allogeneic stem-cell transplantation have a significantly enhanced risk of relapse. Here we present the results of a prospective multicenter study to investigate (1) whether relapse of acute lymphoblastic leukemia (ALL) can be determined in advance by serial analysis of chimerism, and (2) if outcome can be influenced by withdrawal of immunosuppression and/or by low-dose donor lymphocyte infusion when increasing MC is detected.Patients and Methods Serial and quantitative analysis of chimerism was performed using a fluorescent-based short-tandem-repeat-polymerase chain reaction in 163 children with ALL.Results One hundred one patients revealed complete chimerism (CC) or low-level MC (CC/low-level MC); increasing MC was found in 46 patients; and decreasing MC, in 16 patients. Relapse was significantly more frequent in patients with increasing MC (26 of 46) than in patients with CC/low-level MC (eight of 101) or in patients with decreasing MC (0 of 16; P