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红系祖细胞的体外培养生长及血清促红细胞生成素测定在真性红细胞增多症鉴别诊断中的应用

In vitro culture growth of erythroid progenitors and serum erythropoietin assay in the differential diagnosis of polycythaemia.

作者信息

Shih L Y, Lee C T, See L C, Ou Y C, Dunn P, Wang P N, Kuo M C, Wu J H

机构信息

Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan.

出版信息

Eur J Clin Invest. 1998 Jul;28(7):569-76. doi: 10.1046/j.1365-2362.1998.00331.x.

DOI:10.1046/j.1365-2362.1998.00331.x
PMID:9726038
Abstract

BACKGROUND

We assessed the in vitro culture growth of erythroid progenitors [burst forming unit-erythroid (BFU-E)] and serum erythropoietin (EPO) levels in different groups of polycythaemia to determine the discriminative power in differential diagnosis of polycythaemia.

METHODS

We used the methylcellulose culture technique to study the growth of endogenous erythroid colonies (EECs) and EPO-dependent BFU-E from bone marrow (BM) and/or peripheral blood (PB) cells from 40 patients with polycythaemia vera (PV), 13 with secondary polycythaemia (SP), 19 with pure erythrocytosis (PE), five with PE and PV evolution later (PE-PV), and 12 with relative polycythaemia (RP). The serum EPO levels were measured by radioimmunoassay before treatment in 47 patients, 23 SP patients, 19 PE patients, five PE-PV patients and 16 RP patients, as well as after treatment in 38 PV patients, five PE-PV patients and 12 PE patients.

RESULTS

The results of the erythroid progenitor culture assay showed that the numbers of EPO-dependent BFU-E in BM did not differ significantly among groups. The PB BFU-E were significantly higher in PV than in SP or PE, and no statistical difference were found among patients with SP, PE and RP. There was a correlation between BM BFU-E and PB BFU-E in the individual PV and PE patients. EECs were present in all BM and PB cultures of untreated and phlebotomy-treated PV and PE-PV patients, but were absent in 6 of 17 PV patients who had received cytotoxic therapy. EECs were not found in SP, PE and RP. PB could substitute for BM in the EEC or the BFU-E assay. Both pretreatment and post-treatment serum EPO levels of PV and PE-PV were similar, which were significantly lower than SP, PE or RP. The serum EPO levels in treated PV or PE-PV patients who had normal haematocrit values were not significantly different from those in untreated patients. In contrast, the phlebotomy-treated PE patients had significantly higher serum EPO values than untreated PE patients. In the differentiation between PV and PE, the sensitivity, specificity, positive predictive value and negative predictive value of post-treatment serum EPO levels at a cut-off level of < or = 9 UL-1 were 74%, 92% and 52% respectively. The discriminative power of post-phlebotomy serum EPO levels was even higher with a positive predictive value of 80% and negative predictive value of 92% for the prediction of PV evolution in patients with pure erythrocytosis of unknown origin.

CONCLUSION

The present study showed that apart from EEC assay, the post-phlebotomy serum EPO level was a sensitive and specific parameter in the differential diagnosis of polycythaemia, in particular for the identification of PV among patients with unclassifiable polycythaemia.

摘要

背景

我们评估了不同类型红细胞增多症患者中红系祖细胞[红系爆式集落形成单位(BFU-E)]的体外培养生长情况以及血清促红细胞生成素(EPO)水平,以确定其在红细胞增多症鉴别诊断中的鉴别能力。

方法

我们采用甲基纤维素培养技术,研究了40例真性红细胞增多症(PV)患者、13例继发性红细胞增多症(SP)患者、19例单纯红细胞增多症(PE)患者、5例随后演变为PE-PV的患者以及12例相对性红细胞增多症(RP)患者的骨髓(BM)和/或外周血(PB)细胞中内源性红系集落(EEC)和EPO依赖的BFU-E的生长情况。通过放射免疫分析法测定了47例患者(23例SP患者、19例PE患者、5例PE-PV患者和16例RP患者)治疗前以及38例PV患者、5例PE-PV患者和12例PE患者治疗后的血清EPO水平。

结果

红系祖细胞培养试验结果显示,各组骨髓中EPO依赖的BFU-E数量无显著差异。PV患者外周血BFU-E显著高于SP或PE患者,而SP、PE和RP患者之间未发现统计学差异。个别PV和PE患者的骨髓BFU-E与外周血BFU-E之间存在相关性。未治疗及放血治疗的PV和PE-PV患者的所有骨髓和外周血培养物中均存在EEC,但17例接受细胞毒性治疗的PV患者中有6例未检测到EEC。SP、PE和RP患者中未发现EEC。在外周血EEC或BFU-E检测中,外周血可替代骨髓。PV和PE-PV患者治疗前和治疗后的血清EPO水平相似,均显著低于SP、PE或RP患者。血细胞比容值正常的治疗后PV或PE-PV患者的血清EPO水平与未治疗患者无显著差异。相比之下,放血治疗的PE患者血清EPO值显著高于未治疗的PE患者。在PV和PE的鉴别中,治疗后血清EPO水平在临界值≤9 UL-1时的敏感性、特异性、阳性预测值和阴性预测值分别为74%、92%、52%和74%。放血后血清EPO水平的鉴别能力更高,对于不明原因单纯红细胞增多症患者PV演变的预测,阳性预测值为80%,阴性预测值为92%。

结论

本研究表明,除EEC检测外,放血后血清EPO水平是红细胞增多症鉴别诊断中的一个敏感且特异的参数,尤其对于在无法分类的红细胞增多症患者中鉴别PV。

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