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Multicenter Study
. 2019 Oct;103(4):335-341.
doi: 10.1111/ejh.13288. Epub 2019 Jul 26.

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

Tamar Tadmor  1   2 , Andrei Braester  3   4 , Dally Najib  5 , Ariel Aviv  6 , Yair Herishanu  7   8 , Mona Yuklea  9 , Lev Shvidel  10 , Naomi Rahimi-Levene  11 , Rosa Ruchlemer  12 , Ariela Arad  13 , Claudia Fogl  14 , Clara Henig  15 , Mira Barak  15 , Lee Magal  16 , Aaron Polliack  13 , Kelly Townsend  14 ; Israeli CLL study group
Affiliations
Multicenter Study

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

Tamar Tadmor et al. Eur J Haematol. 2019 Oct.

Abstract

Background: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation.

Aims: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL.

Results: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months.

Conclusion: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.

Keywords: CLL; Hevylite; IgG subclasses; free light chains; immunoparesis.

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References

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