Beta‐2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B‐cell lymphoma

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

doi:10.1002/hon.2312

Cited by 30 publications

(36 citation statements)

References 42 publications

(45 reference statements)

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“…However, serum B2M levels also imply involvement of the immune reaction to the tumor because it is a component of major histocompatibility complex (MHC I) (49,50). Based on these grounds, several studies have shown the poor prognostic effect of serum B2M in DLBCL (30,51,52). However, these results are controversial, and most of these studies have shown difficulties in determining the universal optimal cut-off point.…”

Section: Discussionmentioning

confidence: 99%

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

et al. 2020

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The risk stratification of diffuse large B-cell lymphoma (DLBCL) is crucial. The International Prognostic Index, the most commonly used and the traditional risk stratification system, is composed of fixed and artificially dichotomized attributes. We aimed to develop a novel prognostic model that allows the incorporation of up-to-date attributes comprehensively without information loss. We analyzed 204 patients with primary DLBCL who were uniformly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2007 to 2012 at Asan Medical Center. Using the multivariable fractional polynomial (MFP) method and bootstrap resampling, we selected the variables of significance and the best fitted functional form in fractional polynomials. Age, serum β2-microglobulin, serum lactate dehydrogenase, and BCL2 expression were selected as significant variables in predicting overall survival (OS), while age was excluded in predicting 2-years event-free survival. The prognostic score calculated by the MFP model effectively classifies patients into four risk groups with 5-years OS of 89.91% (low risk), 81.21% (low-intermediate risk), 66.40% (high-intermediate risk), and 37.89% (high risk). We suggest a new prognostic model that is simple and flexible. By using the MFP method, we can incorporate various clinicopathologic factors into a risk stratification system without arbitrary dichotomization.

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Section: Discussionmentioning

confidence: 99%

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

et al. 2020

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“…The prognostic role of beta-2 microglobulin in patients with DLBCL treated with rituximab has not been fully investigated in previous studies except for the notable Japanese studies by Kanemsa et al and Miyashita et al [34, 35]. They reported that elevated serum beta-2 microglobulin was a poor prognostic predictor in patients with DLBCL in the rituximab era.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era

et al. 2016

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The prognostic value of serum beta-2 microglobulin for diffuse large B-cell lymphoma (DLBCL) is not well known in the rituximab era. A retrospective registry data analysis of 833 patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was conducted to establish the prognostic significance of serum beta-2 microglobulin at a ≥2.5 mg/L cutoff. Five-year progression-free survival (PFS, 76.1% vs. 41.0%; p < 0.001) and overall survival (OS, 83.8% vs. 49.2%; p < 0.001) were significantly worse in patients with elevated serum beta-2 microglobulin (n = 290, 34.8%). Furthermore, the five parameters of the International Prognostic Index, accompanying B symptoms, bone marrow involvement and impaired renal function were associated with worse PFS and OS. In multivariate analysis, elevated beta-2 microglobulin was a significant poor prognostic factor for PFS (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.29–2.24; p < 0.001) and OS (HR, 2.0; 95% CI, 1.47–2.75; p < 0.001). In an independent validation cohort of 258 R-CHOP treated patients with de novo DLBCL, elevated beta-2 microglobulin levels remained a significant poor prognostic factor for PFS (HR, 2.03; 95% CI, 1.23–3.32; p = 0.005) and exhibited a strong trend of association with worse OS (HR, 1.64; 95% CI, 0.98–2.75; p = 0.062). The significance of serum beta-2 microglobulin levels as an independent prognostic factor for patients with DLBCL receiving R-CHOP is confirmed.

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“…This elevated value is independently associated with unfavorable prognosis of most of the hematological malignancies (269, 273–277). These associations persist despite adjustment for well-validated clinical prognostic scores and therapy indicators (274, 278, 279). …”

Section: β2m In Non-renal Diseasesmentioning

confidence: 97%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

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Beta‐2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B‐cell lymphoma

Cited by 30 publications

References 42 publications

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

Risk Stratification Using Multivariable Fractional Polynomials in Diffuse Large B-Cell Lymphoma

Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

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