Free Light Chain Ratio As a Simple Prognostic Marker in a Single Institution Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5320-5320
Author(s):  
Camila Pena ◽  
Javier Voisin ◽  
Alexis Peralta ◽  
Manuela Ortiz ◽  
Viviana Balboa ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Plasma Cell ◽  
Light Chain ◽  
Staging System ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Staging Systems ◽  
Study Population ◽  
International Staging System

Abstract Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow plasma cell infiltration and the secretion of monoclonal immunoglobulin (Ig) in the serum or urine. Median survival in MM patients is approximately 5 years and significant morbidity may be experienced. The course is progressive and although, always incurable, the prognosis is highly variable. The two more widely used staging systems in MM are by Durie and Salmon and the International Staging System (ISS). Others have been studied, including serum free light chain (sFLC) concentrations and ratio (sFLCr). Methods: We measured sFLC in 27 newly diagnosed MM (21 Intact Ig MM, 5 light chain MM, 1 non secretory MM) at our center (Hospital del Salvador, Santiago de Chile) from October 2013 until June 2015. The sFLCr was calculated with the involved monoclonal light chain as the numerator. The median sFLCr was 17. Patients were divided into a "low group" (<17 sFLCr) and a "high group" (>17 sFLCr). We also analyzed these patients using the cut off (sFLCr of 50) previously reported by Garcia de Veas Silva et al. [Hematology reports 2015; 7 (s1) p23] The median follow-up was 16 months. Results: During the period of study there were 8 deaths (29,7%). Seven (87,5%) of these deaths presented with an ISS score of 3 (table 1). Mortality rates were lower in the group of patients with "low" sFLCr (15,3%, 2 deaths in a group of 13 patients), as compared to patients with a "high" sFLCr (42,9%, 6 deaths in a group of 14 patients) (table 2). Using the cutoff established by Garcia de Veas Silva et al, the mortality rate for patients with sFLCr >50 was 66,7% vs. 11,1% in for patients in the <50 sFLCr group (table 3). Discussion: Although a short follow up period was available for analysis, we believe these results are promising. sFLCr can be used as an easy prognostic indicator in newly diagnosed, symptomatic MM, especially when high risk patients (>50 sFLCr) are identified. The introduction of biomarkers in the evaluation of MM patients will enable better risk assessment and rational follow up. Table 1. International Staging System. Stratification of our study population. ISS N Patients N Deaths Mortality (%) 1 2 0 0 2 12 1 8,3 3 13 7 53,9 Table 2. Mortality rate in our study population using the median sFLCr as a cut off value. Mortality MM N Patients N Deaths Mortality (%) All 27 8 29,6 sFLCr>17 14 6 42,9 sFLCr<17 13 2 15,4 Table 3. Mortality rate in our population using the published cut off sFLCr value. Mortality MM N Patients N Deaths Mortality (%) All 27 8 29,6 sFLCr>50 9 6 66,7 sFLCr<50 18 2 11,1 Disclosures Delgado: The Binding Site: Employment.

scholarly journals Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system

Leukemia ◽  
2008 ◽  
Vol 22 (10) ◽  
pp. 1933-1937 ◽  
Author(s):  
C L H Snozek ◽  
J A Katzmann ◽  
R A Kyle ◽  
A Dispenzieri ◽  
D R Larson ◽  
...  
Keyword(s):  
Light Chain ◽  
Prognostic Value ◽  
Staging System ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
International Staging System

A Comparison of 3 Staging Systems for the Outcome Following Autologous Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5479-5479
Author(s):  
Hee-Jung Sohn ◽  
Kihyun Kim ◽  
Jae-Hoon Lee ◽  
Soo-Mee Bang ◽  
Dong Hwan Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gold Standard ◽  
Staging System ◽  
Stage I ◽  
Event Free Survival ◽  
Free Survival ◽  
Staging Systems ◽  
International Staging System ◽  
Beta 2 Microglobulin

Abstract The Durie-Salmon (DS) stage has been the gold standard for stratification of MM patients. However, the system does not contain beta-2 microglobulin (B2M) widely recognized as the single most powerful prognostic parameter. Recently, The Southwest Oncology Group (SWOG) staging system (Jacobson JL, et al. Br J Haematol122:441–50, 2003) and the International Staging System (ISS) (Greipp PR, et al. J Clin Oncol23:3412–20, 2005) utilizing B2M have been proposed. We aimed to evaluate whether the stage assessed at the time of ASCT by DS, SWOG, or ISS predict outcome following ASCT in patients with MM. Between November 1996 and December 2004, a total of 141 patients with MM who were treated with ASCT at 5 institutions in Korea were available for this analysis. The distribution of patients’ stage at ASCT by 3 staging systems was as Table 1. With a median follow-up of 20 months from ASCT, the median event-free survival (EFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 11–21) and 56 months (95% CI, 38–74), respectively. The median survival of each stage group according to 3 staging systems at ASCT was as Table 2. Differences in EFS among the stage groups were not statistically significant. However, OS after ASCT was dependent on the SWOG stage at the time of ASCT and also significantly longer in patients with ISS stage I than others (NR vs. 39 months, P =.001). In this study, OS following ASCT was influenced by the stage according to SWOG or ISS, but not DS. The distribution of patients by 3 staging systems Stage I II III IV DS 32 (23%) 23 (16%) 86 (61%) - SWOG 53 (38%) 66 (47%) 16 (11%) 6 (4%) ISS 85 (60%) 34 (24%) 22 (16%) - Median event-free survial and overall survival by 3 staging systems Stage I II III IV P EFS=evnet-free survival, OS=overall survival, NR=not reached, * in months EFS* DS 27 17 13 - .40 SWOG 22 15 24 4 .21 ISS 17 13 10 - .63 OS* DS NR 58 40 - .17 SWOG NR 41 32 17 .045 ISS NR 32 40 - .0042

The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1490-1490 ◽  
Author(s):  
Marie-Christine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Nikolitsa Kafasi ◽  
Dimitris Maltezas ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Light Chain ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Prognostic Information ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Poor Outcomes ◽  
Chain Type

Abstract We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine &gt;2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin &lt;10 g/dl, 32% albumin &lt;3.5 g/dl, and 51% bone marrow infiltration ≥50%. The median sFLCR was 6.00 in the 125 kappa-MM, and 46.43 in the 89 lambda-MM patients. With a median follow-up of 16 months (1–105), 88 MM patients with “low” sFLCR had a 3-year disease specific survival (DSS) of 93±4% vs. 63±6% for 126 patients with “high” sFLCR. The corresponding 5-year DSS rates were 83±7% vs. 43±10% (p=0.0001). In multivariate analysis, “high” sFLCR provided prognostic information independent of the value of ISS, as further reflected by the data presented in the table. LDH levels further contributed in the discrimination of prognosis in multivariate analysis: A subgroup of 19 patients (9% of total) with “high” sFLCR plus ISS=3 plus elevated LDH had a 0% projected DSS at 19 months. sFLCR and the previously described models remained predictive of the outcome, if only patients requiring treatment at diagnosis were analyzed. In conclusion, baseline sFLCR appears to be an easily determined, powerful, independent and very promising novel prognostic factor for survival in patients with newly diagnosed MM. Establishment of the optimal cutoff and prospective validation is needed. Its addition to ISS and LDH can identify subgroups of patients with excellent or very poor outcomes. DSS According to the Combined sFLCR and ISS System Patient Subgroup Pts (#,%) 3-yr DSS (%) 5-yr DSS (%) p “Low” sFLCR and ISS &lt;3 61 (29) 95 90 Either “High” sFLCR or ISS=3 96 (46) 82 56 &lt;0.0001 “High” sFLCR and ISS=3 50 (24) 37 24

Discrepancies in Serum Free Light Chain Assays and Immunofixation for Response Evaluation and Prognostication in Plasma Cell Proliferative Disorders

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5099-5099
Author(s):  
Nasir Bakshi ◽  
Nahlah AlGhasham ◽  
Maha Alharbi ◽  
Jalaluddin Bhuiyan ◽  
Ghada Elgohary ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Oligoclonal Bands ◽  
M Spike ◽  
Serial Samples

Abstract Abstract 5099 Plasma cell proliferative disorders are monitored by a variety of methods. Serum protein electrophoresis (SPE), M-spike quantitation and Immunoelectrophoresis (IFE) are commonly assessed in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM) to determine disease progression, response, or relapse. sFLC quantitation provides a rapid indicator of response, detects the rare occurrence of FLC escape, and also allows disease monitoring in the absence of a measurable serum or urine M-spike. To improve sensitivity of response assessment in MM, the International Myeloma Working Group (IMWG) has recently introduced the stringent CR category. However, no formal studies have validated this criterion. Indeed, the role of the sFLC assay has recently been questioned because of the presence of discordant abnormal sFLC ratios in a significant proportion of patients in CR. This could be at least partly explained by the presence of oligoclonal bands in response to therapy, potentially leading to false-positive results. Accordingly it has been recommended that the serum M-spike be used to monitor disease, and that FLC quantitation be used only if there is no measurable disease by electrophoresis and if the monoclonal sFLC concentration is greater than 10 mg/dL in the context of an abnormal FLC ratio. By analyzing serial samples in our patient population we aim to help usefully interpret the sFLC results and in the long run validate the prognostic impact of attaining CR versus CR plus normal sFLC ratio (stringent CR) after therapy in MM. From a total of 566 samples submitted for FLC analysis over 24-month period at our institution, 94 cases were monoclonal (abnormal FLC ratio) with kappa being the involved chain in 63 and lambda in 31 cases. Serial data from 35 multiple myeloma patients were identified by the availability of 3 serum test results (SPE/IFE/sFLC) in at least 3 serial samples that were obtained 3 months to 6 months apart along with treatment outcome details. Kappa and lambda FLC were quantitated using a Siemens BNII® nephelometer and Freelite® reagent sets from The Binding Site, Birmingham, UK; M-spikes were quantitated Capillarys® system and reagent sets (Sebia Electrophoresis, Norcross, GA). The FLC data was analyzed as the involved FLC concentration (iFLC), the difference between the involved and uninvolved FLC concentration (dFLC), and the FLC K/L ratio (rFLC). Treatment modalities included allogeneic, or autologous stem cell transplantation, conventional, bortezomib or lenalidomide containing chemotherapy. There were 16 (45%) cases in which discordance was observed between the three techniques (sFLC/SPE/IFE) during the follow-up. 11/16 (68%) patients were found to have abnormal sFLC with both abnormal FLC ratio and involved chain (FLCi), while no M-band was detected by SPE/IFE. In two cases (13%) the pattern of discrepancy was opposite with IFE found to be positive while rFLC results were within normal range of 0.26 – 1.65 mg/l. In three cases (19%) abnormal FLC ratio was detected with SPE/IFE being normal but the sFLC ratio did not match the myeloma isotype (sFLC ratio <0.26 for kappa and >1.65 for lambda isotype). In a subgroup of patients (n = 4) who relapsed during follow-up from complete remission sequential monitoring of immunofixation and free light chain assays revealed normalization of SPE/IFE with only faint/ doubtful band detected in one while FLC results were abnormal. The variability of the serum M-spike, IFE and FLC measurements confirm the IMWG recommendations for patient monitoring. The free light chain assay ratio is widely reported as a useful marker for a faster detection of remission or progression in myeloma patients. These techniques in reality complement each other and the FLC results need to be interpreted with caution in context of the electrophoresis results in order to determine the status of remission. More sensitive methods such as multiparametric imunophenotyping analysis for minimal residual disease by multiparametric flowcytometry or molecular primer assays may be useful to determine the depth of complete remission as choosing the type of screening test will likely have a relevant impact in clinical decision making in MM. Disclosures: No relevant conflicts of interest to declare.

Unsuppressed serum albumin levels may jeopardize the clinical relevance of the international staging system to patients with light chain myeloma

2018 ◽  
Vol 36 (5) ◽  
pp. 792-800
Author(s):  
Tetsuhiro Kasamatsu ◽  
Shuji Ozaki ◽  
Takayuki Saitoh ◽  
Jun Konishi ◽  
Kazutaka Sunami ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Light Chain ◽  
Clinical Relevance ◽  
Staging System ◽  
International Staging System

A new staging system for radiotherapy-based treatment of hepatocellular carcinoma: A multicenter cohort study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16155-e16155
Author(s):  
Ting-Shi Su ◽  
Shi-Xiong Liang ◽  
Li-Qing Li ◽  
Qiu-Hua Liu ◽  
Xiao-Fei Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
External Validation ◽  
Staging System ◽  
Time Dependent ◽  
Multicenter Cohort Study ◽  
Discriminatory Ability ◽  
Training Cohort ◽  
Multicenter Cohort ◽  
Staging Systems

e16155 Background: External beam radiation therapy has been used as a palliative to radical treatment of hepatocellular carcinoma (HCC) depending on different tumor status, liver function and patient's general state of health. The existing models of HCC staging cannot perfectly predict the prognosis of radiotherapy. In this study, we aimed to set up a new staging system for radiotherapy-based treatment by incorporating bilirubin-albumin (ALBI) grade and tumor status for the prognostic classifications of HCC. Methods: This multicenter cohort study included 878 HCC patients who received radiotherapy-based treatment. A new staging system was established: stage I, solitary nodule without macrovascular invasion or 2-3 nodules with no more than 3.0 cm each other and PS 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with anyone more than 3.0 cm or ≥4 nodules and PS 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion or regional lymph node metastasis or distant metastasis and PS 0-2 (IIIa: ALBI-1 grade; IIIb:ALBI-2 grade); stage IV: ALBI-3 grade without stage I patient or/and PS score 3-4. The new modified staging system and the existing staging systems, such as the BCLC, TNM, CNLC staging systems were used for prognostic analysis. All patients were separated into different stages and substages. The long-term overall survival outcomes and time-dependent receiver operating characteristic (ROC) were analyzed. Results: A training cohort of 595 patients underwent stereotactic body radiotherapy (SBRT) from 2011 to 2017 and an external validation cohort of 283 patients underwent intensity-modulated radiotherapy (IMRT) from 2000 to 2013 were included into establishing and validating the new staging system. In the training cohort, the median follow-up time was 55 months (range, 6–100 months), and the new staging system had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. BCLC staging could not differentiate stage 0 to A, and stage C to D in these selected patients. TNM staging could not completely distinguish stage IIIb to IV, but also stage Ia to Ib. CNLC staging could not differentiate among stage IIIa, IIIb, and IV. In the external validation, the median follow-up time was 95 months (range, 9–120 months), and the new staging system also had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. The new staging system had a better area under curve of time-dependent ROC than BCLC, TNM and CNLC staging in both SBRT and IMRT cohorts. Conclusions: The new modified (Su’s) staging system could provide a good discriminatory ability to separate patients into different stages and substages after radiotherapy treatment. It may be used to supplement the other HCC staging systems.

Impact of Serum Albumin and B2-Microglobulin level on 2-Year Overall Survival among Newly Diagnosed Multiple Myeloma Patients: A retrospective Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sherian Salama ◽  
Rodaina Yousef ◽  
Asma Al Olama ◽  
Mahmoud Marashi ◽  
Hana Salama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Serum Albumin ◽  
United Arab Emirates ◽  
Staging System ◽  
Albumin Level ◽  
Age At Diagnosis ◽  
Newly Diagnosed ◽  
International Staging System ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Background: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Evaluation and initial staging of the disease is made once the diagnosis is confirmed. The recommended staging system is the International Staging System (ISS). Which determines the Myeloma prognosis by 2 factors: beta-2 Microglobulin and Serum albumin. Goal and Objective: The main goal of this study is to assess the effect of Beta-2 microglobulin and Serum albumin on patient’s survival rate with Multiple Myeloma. The secondary objective is to compare the age at diagnosis with other literature. Methodology: The current study was carried out in Hematology Unit, Dubai Hospital, Dubai, Dubai Health Authority (DHA), United Arab Emirates. Chart review was done retrospectively for 49 newly diagnosed patients with Multiple Myeloma diagnosed between the period 2012-2016. Purposive sample was used to those patients who met the inclusion criteria of this study, to be diagnosed and treated in DH. diagnosed and received regular treatment in Dubai Hospital. Results: Medina follow-up of the patients in this study was (12.8) months. The 2-year overall survival rate for patients with Multiple Myeloma (n = 49) was approximately 80%. While, the 2-year OS rate based on Albumin level. Patients with albumin level > 3.5 mg\dl was significantly higher compared to those who had an albumin level <3.5 mg\dl. 100%, 65% respectively, P = 0.033. Moreover, the 2-year OS rate in terms B2MG level. Patients who had a B2MG < 3.5 mg\dl OS was slightly higher compared to those who had (3.5-5.5 and 5.5 mg\dl). OS rate approximately 85 %, 80 % and 75 respectively, P = .737 Conclusion: Multiple myeloma (MM) is a very heterogeneous disease. For this reason, various prognostic factors and staging systems have been developed to predict the disease outcome. International Staging System (ISS) is very useful in determine the survival based on serum β2- microglobulin and serum albumin levels. The age at diagnosis in Dubai hospital, United Arab Emirates is much younger compared to other studies conducted worldwide. The sample used in the study was also highly diverse in terms of culture and nationality. Such diversity is largely typical in Gulf especially in United Arab Emirates. Therefore, this can play important role in age at diagnosis.

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