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[免疫球蛋白重/轻链对的评估(Hevylite检测)——对多发性骨髓瘤分层有何益处?]

[Assessment of Heavy/ Light Chain Pairs of Immunoglobulin (Hevylite assay) -  Benefit for Stratification of Multiple Myeloma?].

作者信息

Ščudla V, Lochaman P, Pika T, Zapletalová J, Minařík J, Bačovský J

出版信息

Klin Onkol. 2015;28(5):359-69.

PMID:26480864
Abstract

BACKGROUND

The aim of the study was the comparison of two novel stratification models in multiple myeloma (MM), ie. according to Avet- Loiseau (A L) and according to Ludwig (L), based on the HLC r index (ratio of serum levels of involved- HLC/ uninvolved HLC, ie. HLC κ/ HLC  λ assessed using ie. nephelometric/turbidimetric technique using specific polyclonal antibodies on a Binding Site SPA(PLUS)) technique) and β(2) microglobulin (β(2) M) with selected prognostic factors (PF) of MM and staging systems according to Durie- Salmon (D S) and International Staging System (ISS).

PATIENTS AND METHODS

In a cohort of 132 patients (94 with IgG and 38 with IgA type of MM) at the time of dia-gnosis, we assessed HLC r, select-ed PF and D S, ISS, A L and L stratification systems.

RESULTS

Unlike in IgA isotype, in IgG isotype we found a significant relationship of HLC r to stratification according to D S and ISS with the difference between A and B substages according to D S (p = 0.049) and between ISS stages 1 vs. 3 (p = 0.001). In the IgG group, there was highly significant relationship of the depth of Hb and albumin decrease and β(2) M increase to the results of stratification according to ISS, A L and L model (p < 0.0001), increase of LDH in the ISS system and A L, and creatinine according to ISS and L but not the relationship of the stages according to any of the stratification systems to the values of FLC r (ratio of serum free light chains κ/ λ of immunoglobulin), thrombocytes and Ca. In the IgA type, there was a significant relationship of the depth of the decrease of Hb, thrombocytes, albumin and increase of β(2) M to the results of stratification according to ISS, A L and L and increase of creatinine in the case of ISS, but not of the values of FLC r, Ca and LDH in the case of any of the stratification systems. The degree of correlation of selected PF, especially of Hb, albumin and β(2) M, event. of thrombocytes, LDH and creatinine to the stages according to ISS and to stage 1-3 according to A L and L model was in IgG vs IgA isotype significantly different (p < 0.0001- 0.030). Staging system according to ISS had proportional distribution of stages 1- 3, whereas in the A L model prevailed in IgA and IgG isotype risk category 2, ie. intermediate-risk (47.3 and 44.7%) and in the L model prevailed risk category 3, ie. high-risk (41.5 and 52.6%) with low count of category 1, ie. low- risk category (23.4 and 10.5%). McNemar- Bowker test of symmetry showed in both types of MM the highest concordance between the stratification according to D S and L in category 3, ie. high-risk (31.9 vs. 28.9%) with overall accord only in 53.2 and 42.1% and with significant shift in the case of IgG isotype only (p = 0.036). In IgG and IgA isotype there was an overall concordance in the distribution of categories 1- 3 according to ISS vs. A L (62.4 and 63.2%) but with significant shift of the stratification (p = 0.002 and 0.028). In the case of IgG and IgA isotype there was a close relationship between the models A L and L (64.5 and 81.6%) with significant stratification shift (p < 0.0001 and 0.030).

CONCLUSION

The new stratification models for MM according to A L and L are easily practically applicable, with close relationship to principal PF but they need separate assessment of IgG and IgA isotypes of MM. The choice of optimal model for routine practice needs a validation study aimed at progression free survival and overall survival.

摘要

背景

本研究旨在比较多发性骨髓瘤(MM)中两种新的分层模型,即根据阿韦 - 洛索(A L)和根据路德维希(L)的模型,基于高分辨率熔解曲线(HLC r)指数(受累 - HLC/未受累HLC的血清水平之比,即使用比浊法/散射比浊法技术,在Binding Site SPA(PLUS)技术上使用特异性多克隆抗体评估的HLC κ/HLC λ)以及β2微球蛋白(β2M)与MM的选定预后因素(PF)以及根据杜里 - 萨尔蒙(D S)和国际分期系统(ISS)的分期系统进行比较。

患者与方法

在一组132例患者(94例IgG型和38例IgA型MM)诊断时,我们评估了HLC r、选定的PF以及D S、ISS、A L和L分层系统。

结果

与IgA亚型不同,在IgG亚型中,我们发现HLC r与根据D S和ISS的分层存在显著关系,D S中A和B亚阶段之间存在差异(p = 0.049),ISS的1期与3期之间存在差异(p = 0.001)。在IgG组中,Hb和白蛋白降低的程度以及β2M升高与根据ISS、A L和L模型的分层结果高度显著相关(p < 0.0001),ISS系统和A L中LDH升高,以及ISS和L中肌酐升高,但根据任何分层系统的分期与游离轻链比(FLC r,免疫球蛋白的血清游离轻链κ/λ之比)、血小板和钙的值无关。在IgA型中,Hb、血小板、白蛋白降低的程度以及β2M升高与根据ISS、A L和L的分层结果存在显著关系,ISS中肌酐升高,但对于任何分层系统,FLC r、钙和LDH的值无关。选定的PF,尤其是Hb、白蛋白和β2M,以及血小板、LDH和肌酐与根据ISS的分期以及根据A L和L模型的1 - 3期的相关性程度在IgG与IgA亚型中显著不同(p < 0.0001 - 0.030)。根据ISS的分期系统,1 - 3期分布成比例,而在A L模型中,IgA和IgG亚型中风险类别2占主导,即中危(47.3%和44.7%),在L模型中风险类别3占主导,即高危(41.5%和52.6%),1类计数低,即低危类别(23.4%和10.5%)。McNemar - Bowker对称性检验表明,在两种类型的MM中,根据D S和L的分层在3类,即高危中一致性最高(31.9%对28.9%),总体一致性仅为53.2%和42.1%,仅在IgG亚型中存在显著偏移(p = 0.036)。在IgG和IgA亚型中,根据ISS与A L的1 - 3类分布总体一致(62.4%和63.2%),但分层存在显著偏移(p = 0.002和0.028)。在IgG和IgA亚型中,A L和L模型之间关系密切(64.5%和81.6%),分层存在显著偏移(p < 0.0001和0.030)。

结论

根据A L和L的MM新分层模型易于实际应用,与主要PF关系密切,但它们需要对MM的IgG和IgA亚型进行单独评估。选择常规实践的最佳模型需要针对无进展生存期和总生存期的验证研究。

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