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BC: Articoli scritti da G. Palladini

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
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
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
Adrenomedullina e peptidi correlati: dalla fisiologia alla diagnostica
Adrenomedullin and related peptides: from physiology to diagnostics
<p>Adrenomedullin (ADM) and related peptides have important physiologic effects on cardiovascular system, including a potent and powerful hypotensive activity caused by dilatation of resistance vessels. Other roles are played in endocrine and nervous systems. The plasma concentrations of ADM are increased in several cardiac diseases, raising the possibility of a role as a biomarker of heart failure. The actions of ADM are generally protective and beneficial to organs and tissues (e.g., vasodilation, natriuresis and anti-inflammation) and suggest that increased ADM expression or activity could act as a compensatory response to end-organ injury. The investigations on the possible applications of ADM in clinical studies have increased since the introduction of an assay measuring mid-regional proadrenomedullin (MR-proADM), a peptide derived from proadrenomedullin characterized by a high stability in plasma. Recent studies suggest that MRproADM could be a marker of adverse prognostic effects after myocardial infarction or during acute cardiac dyspnea. Recently, our group showed that MR-proADM is a powerful prognostic marker in AL (light-chain) amyloidosis, which may not only reflect cardiac dysfunction, but also widespread systemic disease, and can be combined with cardiac troponin for detecting patients at risk of early death. However, further studies are required in order to recommend the assay of MR-proADM in the clinical laboratory; in particular, there is a lack of information about: 1) kinetics of MRproADM release after acute events and 2) the specific contribution given by MR-proADM assay in addition to the wellestablished determination of natriuretic peptides.</p>
Biochimica Clinica ; 37(2) 086-090
Rassegne - Reviews
Un caso di gammopatia monoclonale risolto grazie ai biomarcatori cardiaci
A case of monoclonal gammopathy solved with cardiac biomarkers
Biochimica Clinica ; 35(3) 262