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Editor-in-chief
Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada


Publisher
Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282
email: biochimica.clinica@sibioc.it

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ISSN print: 0393 – 0564
ISSN digital: 0392- 7091



BC: Articoli scritti da G. Merlini

Le gammopatie monoclonali: una sfida continua per la Medicina di Laboratorio
G. Merlini  | 
Biochimica Clinica ; 43(4) 355-356
Editoriale - Editorial
 
Valutazione della risposta alla terapia in un paziente con amiloidosi AL e basse concentrazioni della catena leggera libera monoclonale
Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden
<p>Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden. In patients with light chain (AL) amyloidosis, reduction of amyloidogenic circulating free light chain (FLC) concentration translates in improvement of organ dysfunction and is associated with an increase in overall survival. Validated criteria for hematologic response to therapy are based on FLC quantification. However, patients with a difference between involved and uninvolved FLC (dFLC) &lt;50 mg/L are not evaluable for hematologic response. Here we report the case of a 69 year old man with AL (&lambda;) amyloidosis with renal involvement, presenting a low-FLC burden (dFLC 41 mg/L) at diagnosis. After two lines of treatment, a profound reduction of amyloidogenic FLC (dFLC 0 mg/L) was associated with an improvement of organ dysfunction. This case emphasizes the role of FLC assessment in the monitoring also of patients with a low-dFLC burden.</p><p>&nbsp;</p>
Biochimica Clinica ; 43(1) e4-e6
Casi Clinici - Case Report
 
La misura delle catene leggere libere indentifica la ricaduta di malattia e orienta per una rivalutazione della tipizzazione dell’amiloide in una paziente con amiloidosi AL
Free light measurement identifies relapse and prompts to reconsider amyloid typing in a patient with AL amyloidosis
<p>The detection and quantification of amyloidogenic light-chains (LC) is necessary for diagnosis and evaluation of response in AL amyloidosis. A 69 years old woman was initially diagnosed, in another center, with AL-<span style="font-family:calibri,sans-serif; font-size:11.0pt">&lambda;</span> amyloidosis with renal and soft tissue involvement in December 2001. After 4 cycles of therapy with melphalan and dexamethasone serum and urine immunofixation were negative and, after cycle 6, complete remission was confirmed. Free light chain (FLC) ratio was normal until June 2006, when proteinuria increased, and an elevated k-FLC concentration with abnormal k/<span style="font-family:calibri,sans-serif; font-size:14.6667px">&lambda;</span>-ratio was documented. We repeated the abdominal fat aspirate for amyloid typing by immune-electron microscopy that revealed k-LC deposits. The diagnosis was AL-k. A relapse was documented and the patient was started on bortezomib and dexamethasone therapy. After 8 cycles, complete remission was obtained. In this case, FLC allowed the identification of the amyloidogenic-LC, enabling the detection of relapse.</p>
Biochimica Clinica ; 42(2) e15-e17
Casi clinici - Case report
 
Ruolo del saggio Hevylite® nella diagnosi e nel monitoraggio delle gammopatie monoclonali
Role of Hevylite® assay in the diagnosis and monitoring of monoclonal gammopathies
<p>Clinical tests for detection and characterization of monoclonal immunoglobulins include serum and urine protein electrophoresis, and serum and urine immunofixation. The quantification of monoclonal components provides a surrogate for monitoring the size of malignant cell population in patients affected by plasma cell dyscrasia. As complementary test, immunoglobulin quantification is useful in patients with high concentrations of monoclonal IgG and in patients with monoclonal IgA whose electrophoretic migration is in the -fraction. Serum free light chain / ratio and the concentration of free light chains can also be used in different conditions. To overcome the limitations of traditional methods, e.g., for the quantification of monoclonal components that are indistinguishable from other proteins at electrophoresis, a new nephelometric immunoassay, called Hevylite assay (HLC), was developed. HLC separately measures in pairs light chain types of each intact immunoglobulin class, generating ratios of monoclonal immunoglobulin/uninvolved polyclonal immunoglobulin concentrations. Studies have shown that HLC and immunofixation are complementary methods. In this review, we summarize the role of HLC in the identification of clonality, prediction of prognosis in patients with multiple myeloma and in the evaluation of response to treatment. HLC ratio may also reveal immunoparesis and serve as a new marker for validating remission depth and relapse probability.</p>
Biochimica Clinica ; 40(4) 302-306
Rassegne - Reviews
 
Utilità del saggio Hevylite nella gestione clinica di una paziente affetta da amiloidosi AL con gammopatia biclonale
Usefulness of the Hevylite assay in the management of a patient with AL amyloidosis and biclonal gammopathy
<p>Patients with AL amyloidosis often have small monoclonal components (MCs) difficult to quantify by densitometry. IgA are the most problematic, due to anodic migration and possible masking under proteins migrating in &beta; zone. We evaluated the usefulness of the Hevylite assay (Binding Site, Birmingham UK), at diagnosis and during follow-up, in a patient with AL amyloidosis and biclonal gammopathy. At diagnosis serum immunofixation identified an IgG&lambda; and an IgA&lambda; band (the last one not reliably quantifiable in capillary electrophoresis). The &kappa; serum free light chain (FLC) concentration was 4.94 mg/L and &lambda; 26 mg/L (&kappa;/&lambda; ratio 0.19). The Hevylite test showed both IgG&lambda; and IgA&lambda; above the reference limits, with abnormal &kappa;/&lambda; ratios. After treatment, a 27% decrease in IgG&lambda; and a 56% decrease in IgA&lambda; concentration were documented by Hevylite, which was the only mean to quantify the monoclonal components in this patient.</p>
Biochimica Clinica ; 40(2) e12-e15
Casi clinici - Case report
 
Identificazione di danno renale reversibile e di precoce risposta alla chemioterapia in pazienti con amiloidosi AL
Identification of reversible renal damage and early response to chemotherapy in AL amyloidosis
<p>The kidney&nbsp;is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or&nbsp;reversibility of renal involvement. Furthermore, criteria for renal response have never been validated. We designed a&nbsp;staging system for renal damage and identified criteria for renal response and progression in a population of 732&nbsp;newly diagnosed patients with AL amyloidosis. The population was composed of 461 patients from Pavia (testing&nbsp;cohort) and 271 subjects from Heidelberg (validation cohort). Baseline proteinuria &gt;5 g/24 h and estimated glomerular&nbsp;filtration rate (eGFR) &lt;50 mL/min/1.73 m<sup>2</sup> were independently associated with poorer renal survival and discriminated&nbsp;between 3 stages (with none, one or two markers above the cut-off) with significant different renal survival. At 6-month&nbsp;follow-up, a &ge;25% eGFR decrease predicted poor renal survival in both cohorts and was adopted as criterion for renal&nbsp;progression. A decrease in proteinuria &ge;30% or below the cut-off of 0.5 g/24 h in absence of renal progression were&nbsp;the criteria for renal response, being associated with longer renal survival in the testing and validation cohorts. These&nbsp;endpoints can be used as validated response criteria in renal AL amyloidosis, allowing early assessment of treatment&nbsp;efficacy.</p>
Biochimica Clinica ; 40(1) 21-27
Contributi scientifici - Scientific Papers
 
Valutazione dell’impatto delle raccomandazioni del Gruppo di Studio SIBioC Proteine sull’operatività dei laboratori italiani
Evaluation of the impact of recommendations by the SIBioC Proteins Study Group on Italian laboratory procedures
<p>Protein diagnostics is central in the management of subjects with monoclonal gammopathy. Laboratory&nbsp;should provide the most useful information to ensure the best patient outcome. To assess if recommendations issued&nbsp;after the 2007 survey have impacted on Italian laboratories contributing to a better harmonization of the post-analytical&nbsp;phase, the SIBioC Proteins Study Group has repeated a similar survey in February 2015. Twenty questions were&nbsp;electronically submitted to all SIBioC members using the software &quot;Survey monkey&quot;. 103 responses were collected,&nbsp;corresponding to ~6% of Italian laboratories. 47% of laboratories add an appropriate comment to the serum protein&nbsp;electrophoresis report when no monoclonal component (MC) is detected (36% in 2007). MC are correctly defined by&nbsp;63% of the laboratories; however, 11% reports MC as &ldquo;thickening&rdquo; or &ldquo;asymmetry&rdquo; or &ldquo;homogeneous peak&rdquo;. These&nbsp;ambiguous terms were used by roughly the same percentage (14%) in 2007. In 2015, the number of laboratories&nbsp;performing a MC typing only when requested by the clinician is reduced by 10% when compared to 2007. In both&nbsp;surveys, the percentage of laboratories performing and reporting the MC quantification is 77%. The worse results were&nbsp;obtained for Bence Jones protein (BJP) determination (not investigated in 2007): only 66% of laboratories utilize the&nbsp;immunofixation to detect the BJP and 57% do not quantify the protein. Although some progresses in harmonization of&nbsp;reporting are observed in CM testing over years, there is still room for significant improvement.</p>
Biochimica Clinica ; 39(6) 585-590
Contributi scientifici - Scientific Papers
 
Amiloidosi AL: il cuore del problema
AL amyloidosis: the heart of the problem
<p>Immunoglobulin light chain amyloidosis (AL) is characterized by the&nbsp;production of immunoglobulin light chains with conformational abnormalities that cause systemic toxicity with rapid&nbsp;deterioration of the function of vital organs. When the heart is involved, as it is the case in ~3/4 of patients, clinical signs&nbsp;and symptoms often appear when organ damage is already irreversible and the treatment cannot longer change the&nbsp;course of disease. Although in recent years new powerful therapeutic regimens have become available, which are able&nbsp;to significantly improve long-term survival, the mortality rate in the first year after diagnosis has indeed not improved, still&nbsp;being 25-30%. Cardiac involvement is responsible for almost all of these deaths. Early diagnosis based on biochemical&nbsp;markers of the disease rather than on clinical symptoms and signs can allow for early detection of patients with cardiac&nbsp;amyloidosis and to establish an effective therapy. To this end, our group has proposed the introduction of the&nbsp;measurement of natriuretic peptides that can identify the presence of amyloid cardiomyopathy with a sensitivity of 100%&nbsp;in the monitoring of subjects with monoclonal gammopathies of undetermined significance (MGUS) and altered ratio of&nbsp;circulating free light chains (FLC). Individuals with MGUS and altered FLC ratio are at intermediate/high risk of&nbsp;developing a malignant disease (AL amyloidosis in 10-15% of cases) and, according to the guidelines of the International&nbsp;Myeloma Working Group, they should be monitored regularly for their entire life. Here we describe a case where the&nbsp;application of these recent recommendations has allowed the timely recognition of amyloid cardiomyopathy.</p>
Biochimica Clinica ; 39(3) 220-222
Casi clinici - Case report
 
Casi clinici: un approccio nuovo per Biochimica Clinica, uno strumento utile per i professionisti di laboratorio
Case reports: a new approach by Biochimica Clinica, a useful tool for laboratory professionals
Biochimica Clinica ; 39(1) 015-016
Editoriale - Editorial
 
Documento di consenso SIBioC e Società Italiana di Radiologia Medica (SIRM) sulla richiesta di esami di laboratorio per la valutazione del danno renale da mezzi di contrasto
SIBioC-SIRM consensus document on the request of laboratory tests for evaluation of contrast media nephrotoxicity
<p>The contrast media, widely used in imaging diagnostics, show a favorable safety profile. As the&#160;presence of pre-existing disease is considered a risk factor for adverse events, patients should be carefully evaluated&#160;prior to the procedure. The aim of this consensus document is to recommend appropriate biochemical tests to be&#160;performed for an early recognition of individuals at higher risk of contrast media nephrotoxicity. This condition is defined&#160;by an increase of serum creatinine concentrations of at least 0.50 mg/dL and/or 25% within 3-4 days from contrast media&#160;exposure. The most important risk factor is renal insufficiency [estimated glomerular filtration rate (eGFR) &lt;60&#160;mL/min/1.73 m<sup>2</sup> or serum creatinine &gt;1.50 mg/dL]. Other risk factors are age &gt;75 years, dehydration, diabetes, heart&#160;failure and anemia. Monoclonal gammopathies, multiple myeloma, Waldenstr&#246;m macroglobulinemia and amyloidosis&#160;are not considered risk factors per se. On the basis of available guidelines, it is recommended: a) prior to the&#160;examination, to measure serum creatinine baseline with a method traceable to the international reference measurement&#160;system and report its concentration together with the eGFR using the Chronic Kidney Disease &#8211; Epidemiology&#160;Collaboration (CKD-EPI) equation; b) for monitoring, to measure serum creatinine more than once calculating the delta&#160;from the baseline value: if serum creatinine increases &gt;5%, repeat the test within 48-72 h. Performing of laboratory tests&#160;to exclude the presence of monoclonal gammopathies (i.e., serum protein electrophoresis, Bence Jones protein&#160;determination, serum free light chain measurements) is not required.</p>
Biochimica Clinica ; 38(2) 139-142
Documenti SIBioC - SIBioC Documents
 
Le analisi personalizzate nella Medicina di Laboratorio
G. Merlini  | 
Biochimica Clinica ; 38(2) 159-160
Recensioni - Book review
 
Il contributo della diagnostica proteica nella gestione delle gammopatie monoclonali
Protein diagnostics in the management of monoclonal gammopathies
<p>This document examines laboratory tests&nbsp;to be used for the management of monoclonal gammopathies in different clinical scenarios, from screening to&nbsp;monitoring and assessment of the response to therapy. The content is based on international recommendations and&nbsp;guidelines currently available. It includes sections on the analytical aspects of different tests&nbsp;(serum&nbsp;protein&nbsp;electrophoresis, typing and quantification of monoclonal components, Bence Jones protein determination and free&nbsp;light chain measurement) and on their clinical significance as well. Different clinical settings are examined: screening,&nbsp;diagnosis, risk stratification, monitoring and response assessment. For each of those, laboratory tests to be used are&nbsp;indicated. Aim of the document is to help clinical laboratories avoiding unnecessary tests, ensuring in the meantime&nbsp;that all the investigations required for a optimal patient management are carried out.</p>
Biochimica Clinica ; 38(1) 47-53
Documenti SIBioC - SIBioC Documents
 
Componenti monoclonali piccole ma dannose
Small but harmful monoclonal components
<p>A small B-cell clone can synthesize a toxic monoclonal protein that&nbsp;causes severe organ damage. Diseases caused by these toxic immunoglobulins range from AL amyloidosis, light&nbsp;chain deposition disease and cryoglobulinemia to the POEMS (Polineuropathy, Organomegaly, Endocrinopathy,&nbsp;Monoclonal protein and Skin changes) syndrome. The serum monoclonal components are, in these cases, usually&nbsp;small and difficult to be detected by the commercially available methods. However, an early detection and a correct&nbsp;characterization of the monoclonal component is essential, because misdiagnosis or a delay in diagnosis can prevent&nbsp;the proper treatment of the patient worsening his outcome. Here we present two cases of amyloidosis AL, where the&nbsp;correct diagnosis was facilitated by specific and sensitive techniques. This does not mean that every clinical&nbsp;laboratory should be competent in this field and use these methods routinely, but simply that people should be aware&nbsp;of the problem, so that these clinical conditions can be properly managed.</p>
Biochimica Clinica ; 37(5) 431-434
Casi clinici - Case Report
 
Le catene leggere libere circolanti nella gestione del paziente con amiloidosi AL
Free light chain (FLC) assays in the management of patients with AL amyloidosis
<p>In light chain (AL)&nbsp;amyloidosis monoclonal FLC are not only a marker of the disease, but the toxic agent responsible for the organ&nbsp;damage. The possibility of measuring FLC provides an extraordinary means for managing AL amyloidosis. The&nbsp;quantitation of FLC, together with immunofixation of both serum and urine, allows optimal (98%-100%) sensitivity in&nbsp;detecting the amyloidogenic monoclonal protein. In combination with cardiac troponins and amino-terminal pronatriuretic&nbsp;type B peptide, FLC measurement grants an accurate prognostic stratification, which is important both in&nbsp;tailoring the therapeutic approach in individual patients and in designing and interpreting clinical trials. Chemotherapy&nbsp;targeting the amyloidogenic plasma cell clone succeeds in restoring organ function and prolonging survival only if it&nbsp;obtains a marked and persistent reduction of FLC, so much so that current response criteria are based on FLC<br />measurement.</p>
Biochimica Clinica ; 37(5) 347-351
Rassegne - Reviews
 
Perché è importante identificare e segnalare le piccole componenti monoclonali
Small monoclonal immunoglobulins should not be neglected
G. Merlini  | 
<p>The detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing systemic damage and protean clinical presentations.The monoclonal protein can aggregate and deposit systemically as occurs in light-chain amyloidosis, monoclonal immunoglobulin deposition disease, and monoclonal cryoglobulinemia.The clone synthesizing noxious monoclonal proteins is often small and sensitive techniques may be required to detect these immunoglobulins. A delay in diagnosis can cause irreversible organ damage and dramatically shorten survival. Prompt recognition of suggestive signs and symptoms should trigger a thorough diagnostic approach to reach the correct diagnosis quickly, as this is the key to effective therapy.</p>
Biochimica Clinica ; 36(1) 25-28
Opinioni - Opinions
 
Un caso di gammopatia monoclonale risolto grazie ai biomarcatori cardiaci
A case of monoclonal gammopathy solved with cardiac biomarkers
Biochimica Clinica ; 35(3) 262
CASI CLINICI - CASI CLINICI
 
La misura delle catene leggere libere delle immunoglobuline nel siero: aspetti analitici e clinici
Determination of free light chains in serum: analytical and clinical aspects
Biochimica Clinica ; 34(1) 26
RASSEGNE - RASSEGNE