骨髓中可溶性55千道尔顿肿瘤坏死因子受体亚型的水平与急性淋巴细胞白血病首次复发患儿的临床结局相关。

Levels of the soluble, 55-kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence.

作者信息

Wu Shuling, Korte Alexander, Gessner Reinhard, Henze Guenter, Seeger Karlheinz

机构信息

Department of Pediatric Oncology/Hematology, Charité Medical Center, Humboldt University Berlin, Berlin, Germany.

出版信息

Cancer. 2003 Aug 1;98(3):625-31. doi: 10.1002/cncr.11553.

DOI:10.1002/cncr.11553

PMID:12879482

Abstract

BACKGROUND

It has been shown that the soluble, 55-kilodalton isoform of tumor necrosis factor receptor (sTNFRp55) enhances tumor survival by exhibiting competitive ligand binding. The objective of the current study was to determine the levels of sTNFRp55 and their impact on outcome in 106 children with acute lymphoblastic leukemia (ALL) in first recurrence.

METHODS

Between January 1997 and December 2001, bone marrow (BM) samples were collected from 106 children with a first recurrence of ALL at diagnosis. These patients were enrolled in the Berlin-Frankfurt-Münster (BFM) ALL recurrence trial, ALL-REZ BFM 90-96. Levels of sTNFRp55 in BM samples were determined with a commercially available enzyme-linked immunosorbent assay kit. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate.

RESULTS

The mean sTNFRp55 level (+/- standard deviation) was 3.40 +/- 2.57 ng/mL. High levels of sTNFRp55 were associated with shorter duration of first complete remission and observation time as well as poor response to chemotherapy. Most importantly, the probability of EFS (pEFS) at 3 years was significantly worse for children with recurrent ALL who had sTNFRp55 levels greater than the median value (> 2.77 ng/mL) compared with patients who had levels that were less than the median value (pEFS: 0.44 +/- 0.10 ng/mL vs. 0.12 +/- 0.10 ng/mL; P = 0.006). It is noteworthy that the sTNFRp55 levels in 22 children with recurrent, TEL-AML1-positive ALL ([t(12;21)(p13;q22)]; 2.69 +/- 1.05 ng/mL) were significantly lower compared with the levels in children who had TEL-AML1-negative ALL (3.34 +/- 1.49 ng/mL; P < 0.05).

CONCLUSIONS

The results indicated that a high sTNFRp55 level represents a negative prognostic factor for children with recurrent ALL in terms of EFS and overall survival.

摘要

背景

已表明肿瘤坏死因子受体的可溶性55千道尔顿异构体（sTNFRp55）通过竞争性配体结合增强肿瘤存活。本研究的目的是确定106例首次复发的急性淋巴细胞白血病（ALL）儿童中sTNFRp55的水平及其对预后的影响。

方法

1997年1月至2001年12月期间，收集了106例诊断时首次复发ALL的儿童的骨髓（BM）样本。这些患者参加了柏林-法兰克福-明斯特（BFM）ALL复发试验ALL-REZ BFM 90-96。使用市售的酶联免疫吸附测定试剂盒测定BM样本中sTNFRp55的水平。无事件生存期（EFS）和总生存期根据研究入组日期或随机分组日期（视情况而定）进行评估。

结果

sTNFRp55的平均水平（±标准差）为3.40±2.57 ng/mL。sTNFRp55水平高与首次完全缓解持续时间和观察时间短以及化疗反应差相关。最重要的是，复发ALL且sTNFRp55水平高于中位数（>2.77 ng/mL）的儿童3年无事件生存概率（pEFS）明显低于sTNFRp55水平低于中位数的患者（pEFS：0.44±0.10 ng/mL对0.12±0.10 ng/mL；P = 0.006）。值得注意的是，22例复发的TEL-AML1阳性ALL（[t(12;21)(p13;q22)]）儿童的sTNFRp55水平（2.69±1.05 ng/mL）明显低于TEL-AML1阴性ALL儿童的水平（3.34±1.49 ng/mL；P < 0.05）。