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      Serum beta-2 microglobulin in malignant lymphomas: an old but powerful prognostic factor

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          Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its potential role as a convenient and non-invasive prognostic indicator in malignant lymphomas, the influence of serum β2 microglobulin is currently underestimated, and therapeutic decision making is rarely affected by this marker. Recent studies that included relatively large numbers of patients with specific histologic subtypes showed that serum β2 microglobulin is a potent prognostic marker in malignant lymphomas. In follicular lymphoma, this effort led to the incorporation of serum β2 microglobulin as an indicator in a new prognostic model. In this review, we summarize the current evidence supporting the role of serum β2 microglobulin as a prognostic factor in patients with malignant lymphoma and discuss perspectives for future investigations.

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          Most cited references 30

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          Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study.

          Patients with natural killer T (NK/T) -cell lymphomas have poor survival outcome, and for this condition there is no optimal therapy. The purpose of this study was to design a prognostic model specifically for extranodal NK/T-cell lymphoma, which can identify high-risk patients who need more aggressive therapy. This multicenter retrospective study was comprised of 262 patients who were diagnosed with NK/T-cell lymphoma. After a median follow-up duration of 51.2 months, 5-year overall survival rate in 262 patients was 49.5%. Prognostic factors for survival were "B" symptoms (P = .0003; relative risk, 2.202; 95% CI, 1.446 to 3.353), stage (P = .0006; relative risk, 2.366; 95% CI, 1.462 to 3.828), lactate dehydrogenase (LDH) level (P = .0005; relative risk, 2.278; 95% CI, 1.442 to 3.598), and regional lymph nodes (P = .0044; relative risk, 1.546; 95% CI, 1.009 to 2.367). Of 262 patients, 219 had complete information on four parameters. We identified four different risk groups: group 1, no adverse factor; group 2, one factor; group 3, two factors; and group 4, three or four factors. The new model showed a superior prognostic discrimination as compared with the International Prognostic Index (IPI). Notably, the distribution of patients was balanced when a new model was adopted (group 1, 27%; group 2, 31%; group 3, 20%; group 4, 22%), whereas 81% of patients were categorized as low or low-intermediate risks using IPI. The newly proposed model for extranodal NK/T-cell lymphoma demonstrated a more balanced distribution of patients into four groups with better prognostic discrimination as compared with the IPI.
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            Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project.

            The aim of the F2 study was to verify whether a prospective collection of data would enable the development of a more accurate prognostic index for follicular lymphoma (FL) by using parameters which could not be retrospectively studied before, and by choosing progression-free survival (PFS) as principal end point. Between January 2003 and May 2005, 1,093 patients with a newly diagnosed FL were registered and 942 individuals receiving antilymphoma therapy were selected as the study population. The variables we used for score definition were selected by means of bootstrap resampling procedures on 832 patients with complete data. Procedures to select the model that would minimize errors were also performed. After a median follow-up of 38 months, 261 events for PFS evaluation were recorded. beta2-microglobulin higher than the upper limit of normal, longest diameter of the largest involved node longer than 6 cm, bone marrow involvement, hemoglobin level lower than 12 g/dL, and age older than 60 years were factors independently predictive for PFS. Using these variables, a prognostic model was devised to identify three groups at different levels of risk. The 3-year PFS rate was 91%, 69%, and 51% for patients at low, intermediate, and high risk, respectively (log-rank = 64.6; P < .00001). The 3-year survival rate was 99%, 96%, and 84% for patients at low, intermediate, and high risk, respectively (P < .0001). Follicular Lymphoma International Prognostic Index 2 is a simple prognostic index based on easily available clinical data and may represent a promising new tool for the identification of patients with FL at different risk in the era of immunochemotherapy.
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              High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine.

              To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.

                Author and article information

                Blood Res
                Blood Res
                Blood research
                Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis
                September 2014
                25 September 2014
                : 49
                : 3
                : 148-153
                Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                Author notes
                Correspondence to Cheolwon Suh, M.D., Ph.D. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3209, Fax: +82-2-3010-6961, csuh@ 123456amc.seoul.kr

                #Changhoon Yoo and Dok Hyun Yoon equally contributed to this work.

                © 2014 Korean Society of Hematology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Review Article

                prognostic factor, lymphoma, beta-2 microglobulin


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