International Journal of Clinical & Laboratory Research, Dec 1, 1993
The high frequency of liver involvement in cryoglobulinemia is well established. Although both et... more The high frequency of liver involvement in cryoglobulinemia is well established. Although both etiology and pathogenesis have remained so far undefined, recent studies suggest an association of mixed cryoglobulinemia with hepatitis C virus infection. To explore this hypothesis further, we assessed the prevalence of hepatitis C virus antibodies and RNA in a large group of patients, including: (1) 35 patients with cryoglobulinemia without clinical evidence of liver involvement (group 1), (2) 15 patients with symptomatic cryoglobulinemia associated with chronic liver disease (group 2) and (3) 12 patients with asymptomatic cryoglobulinemia associated with chronic liver disease (group 3). Anti-hepatitis C virus antibodies were detected by a second-generation enzyme-linked immunosorbent assay and third-generation immunoblot (SIA Prototype RIBA), whereas the polymerase chain reaction was used for the detection of viral RNA. Anti-hepatitis C virus antibodies, as detected by enzyme-linked immunosorbent assay, were demonstrated in 21 (60%) patients from group 1, 11 (73.3%) from group 2 and 10 (83.3%) from group 3. The immunoblot identified as positive 3 further patients in group 1 (giving a prevalence of 68.6%) and all patients in groups 2 and 3. Hepatitis C virus RNA was demonstrated in cryoprecipitates from 21 of 24 immunoblot-positives and from 6 of 11 immunoblot-negatives, indicating an actual active viral replication in 77.1% of group 1. This was also found in 13 (86.7%) and 10 (83.3%) cryoprecipitates of groups 2 and 3, respectively. Type II cryoglobulinemia was the prevalent form in group 1 (88.6%) and group 2 (73.3%), whereas type III was found in group 3 (58.3%) and in 26.7% of group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monot... more 6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monotherapy over 6 months, showed 47% overall response rate (ORR) in patients (pts) with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab (FA-ref), or to fludarabine with bulky (>5cm) lymphadenopathy (BF-ref). The effects of ofa retreatment (retx) and maintenance (mt) are unknown. Methods: Pts who responded to ofa and then progressed or had stable disease (SD) in Study 406, were offered retx in Study 416 (NCT00802737; GSK/Genmab) with ofa 1 x 300 mg + 7 x 2000 mg weekly followed by mt with ofa 2000 mg monthly for up to 2 years (if SD or better). Primary endpoint was ORR (1996 NCI-WG). Safety and time to event outcomes were also assessed. Results: Of 29 pts enrolled, 7 had SD and 22 had partial response (PR) and progressed in Study 406. Pts were defined per Study 406: 17 FA-ref, 11 BF-ref, 1 “other”. Pretreatment characteristics were similar between groups. Pts received a median of 12 doses (range 3-32); 86% had 8 doses, 3% received all 32 doses. 72% of pts had infusion-related adverse events (AEs), 41% at 1st infusion, mostly grade 1-2. The most common grade >3 AE occurring up to 60 days after last tx was infection (38%); the most common was pneumonia (17%). 3 pts (10%) had fatal infections, all bronchopneumonia. Clinical efficacy is shown in Table. Comparative analysis to Study 406 is ongoing. Conclusions: The response to ofatumumab (ofa) as induction retreatment and progression-free survival in this limited number of pts was similar to 1st treatment (Study 406). Ofa maintenance had some clinical benefit for pts with advanced CLL. Ofa was well-tolerated with no unexpected toxicities. [Table: see text]
Abstract 3020 Background. In patients with newly diagnosed MM, three/four-drug combinations seem ... more Abstract 3020 Background. In patients with newly diagnosed MM, three/four-drug combinations seem to be more effective compared with two-drug associations in terms of both rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) are still unknown. Methods. This is a multicenter, phase II study including patients with r-rMM having measurable disease, no more than 4 prior lines of therapy, adequate performance status, cardiac and liver function. As induction therapy patients received 6 28-day cycles of oral thalidomide 100 mg/day continuously at bedtime, oral dexamethasone 20 mg on day 1–2, 4–5, 8–9, 11–12, pegylated Liposomal Doxorubicin (pLD) 30 mg/m2 iv on day 4 and bortezomib 1.3 mg/m2 iv on day 1, 4, 8, 11 (ThaDD-V). As consolidation patients underwent 6 28-day cycles of rotating bortezomib 1.3 mg/m2 iv on day 1, 4, 8, 11 plus oral dexamethasone 20 mg on day 1–2, 4–5, 8–9 (3 courses) or thalidomide 100 mg/day continuously at bedtime plus oral dexamethasone 20 mg on day 1–4 (3 courses). Patients eligible and having suitable stem cell storage underwent ASCT instead of standard consolidation at the discretion of attending physician. Maintenance therapy included thalidomide 100 mg/day until relapse or intolerable toxicity. Since in the first 20 patients we recognized an excess of peripheral neuropathy, protocol was amended as follow: bortezomib 1.3 mg/m2 on day 1, 4, 11 and thalidomide 50 mg/day in all therapeutic phases. The primary end-points of this study were best response and toxicity of the planned therapy. Results. Forty-six patients were enrolled. Median age was 63.5 years (range 31–80 years) and the median number of prior regimens was 1 (range 1–4). Twenty-four patients (52%) had undergone autologous stem cell transplantation, 30 (65%) had received anthracyclines, 27 (59%) thalidomide, 8 (17.5%) bortezomib and 16 (35%) were refractory to the last regimen. After induction 16 patients (34.5%) achieved CR (6=13% sCR), 15 (32.5%) VGPR and 4 (8.5%) PR with a ORR of 76.5%. Seven patients (15%) progressed. Out of 46 patients undergone induction, 26 (20 standard, 6 ASCT) received consolidation therapy since 1 patients died during induction, 8 had progressive disease, 1 had second neoplasm, 7 had severe toxicities and 3 undergone allogeneic stem cell transplantation. Excluding 6 patients who have obtained sCR before, 5 (25%) out of 20 patients had further improvement in response. Therefore, best response after induction and consolidation were: 25 CR (54%; 8 sCR=17.5%), 16 VGPR (34.5%) and 2 PR (4.5%). Maintenance therapy did not further improve response. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p= 0.010) whereas prior ASCT, thalidomide or bortezomib, refractory disease and bortezomib dose-intensity did not affect quality of response. After a median follow-up of 31 months (range 12–53), 28 patients relapsed and 20 died. Median TTP was 18.5 months, median PFS was 17.5 months and median survival was 40 months. Median TTP of patients achieving PR-VGPR was 16 months (3 years= 10%) whereas in those obtaining CR it was 32.5 months (3 years= 45%; p=0.032) vs not reached (3 years= 85%) in patients achieving sCR (p=0.003). Main toxicity was peripheral neuropathy (PN). Indeed, in the first 20 patients we observed 6 (30%) grade 2 and 3 (15%) grade 3 PN. After amendment, grade 2 and 3 PN occurred in 3 (11.5%) and 2 patients (7.5%), respectively. DVT occurred in 2 patients (4.5%) and severe infection in 7 (15%). Grade 3–4 neutropenia, anemia and thrombocytopenia occurred in 4 (8.5%), 2 (4%) and 7 patients (15%), respectively. Finally, only one patients died of myocardial infarction during induction. During consolidation therapy other 2 patients developed grade 3 peripheral neuropathy. During maintenance with thalidomide no patients developed severe neuropathy requiring discontinuation. Conclusions. Multi-drug combination namely ThaDD-V as induction followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses are still possible. A reduced dose-intensity of bortezomib significantly decreases PN without jeopardizing outcome. Disclosures: Offidani: Celcene, Janssen Cilag: Honoraria. Polloni:Celgene: Honoraria. Corvatta:Celgene: Honoraria. Gentili:Celgene: Honoraria. Brunori:Celgene, Janssen-Cilag: Honoraria. Catarini:Cerlgene, Janssen-Cilag: Honoraria. Malerba:celgene, Janssen-Cilag: Honoraria. Leoni:Celgene, Janssen-Cilag: Honoraria.
Quantitative measurements of circulating free immunoglobulin light chains (FLC) and of biomarkers... more Quantitative measurements of circulating free immunoglobulin light chains (FLC) and of biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins (cTnT and cTnI) are the expression of recent diagnostic and prognostic advances in AL amyloidosis. Here, we report a patient diagnosed as having AL amyloidosis involving heart, kidney and soft tissue, in association with immunoglobulin D multiple myeloma (MM). This is an extremely rare disease, mostly associated with a poor prognosis. In our patient, the front-line therapy with thalidomide and dexamethasonewasearly discontinued becauseof toxicity,whereas thesecond-line therapywith melphalan and dexamethasone produced complete hematological response and improvement in the involved organs, still maintained after a 3.10 year followup. Circulating FLC, NT-ProBNP and cTnI were measured in the context of diagnostic and monitoring assessments, demonstrating a significant progressive reduction of lambda FLC and NT-ProBNP that could be related to the treatment response and long survival. Introduction: AL amyloidosis, characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissue, mostly occurs in association with a plasma cell dyscrasia. IgD multiple myeloma (MM) is an extremely rare disease, accounting for 2% of all MM cases in which AL amyloidosis, Bence-Jones lambda light chain proteinuria and renal function impairment appear to be particularly frequent [1]. The pathological light chains, responsible for the organ dysfunction in patients with AL amyloidosis, can be estimated by measuring circulating biomarkers. In particular, determining serum levels of free Ig light chains (FLC) improves diagnosis and it is a powerful tool for assessment of treatment response and as predictor of prognosis [2]. In the patients with cardiac involvement, circulating levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and cardiac troponins (cTnT and cTnI) are highly specific markers of myocardial injury, and changes in their concentrations following treatment provide prognostic informations [3,4]. Here, we describe the clinical and laboratory findings of a 61-year-old woman, referred in 2006 to the nephrology clinic because of nephrotic-range proteinuria (24-hr urinary protein 3.96 g/dl), serum creatinine 0.7 mg/dl and creatinine clearance 48 ml/min. Her medical history included carpal tunnel syndrome at her right hand (for which she had undergone surgery 6 months before) and arterial hypertension since 1993. Our aim was to show the diagnostic and prognostic relevance of circulating FLC and cardiac biomarkers in AL amyloidosis. Methods: Our patient was investigated for suspicion of AL amyloidosis. Diagnostic work-up and prognostic evaluation included renal and bone marrow (BM) biopsies, serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), immunonephelometric Ig serum FLC immunoassay (FREELITE, The Binding Site Ltd, Birmingham, UK), 24h-urine electrophoresis (UPE), urine IFE, beta2-microglobulin, and determination of cardiac biomarker levels (i.e. NT-proBNP and cTnI). Results and discussion: Renal biopsy demonstrated homogeneous mesangial and sub-endothelial AL amyloid deposition, producing apple-green birifrangence under polarized light when stained with Congo-red dye; immunofluorescence showed bright staining for lambda light chain. SPE disclosed a monoclonal band (0.27 g/ dl) in the beta region, that on IFE resulted in IgD isotype with lambda light chain restriction. Bence-Jones proteinuria of lambda type was demonstrated by UPE. BM biopsy disclosed 50% infiltration by plasma cells with lambda chain restriction, exhibiting cytoplasmic azurophilic granules. Serum lambda FLC were increased to 9.4 mg/dl (normal range, 0.5–2.6 mg/dl), whereas kappa FLC were 0.8 mg/dl (normal range, 0.3–1.9 mg/dl). Fine-needle aspiration of abdominal fat did not result diagnostic. Electrocardiography showed the presence of low voltage in all limb leads; echocardiography revealed ‘ground glass’ appearance, interventricular septal thickness 17 mm, wall thickness 12 mm, and left ventricular 45% EF; doppler echocardiography detected evidence of grade II diastolic dysfunction; holter-ECG did not show complex ventricular arrhythmias. The serum concentration of NT-ProBNP was increased to 3096 pg/ml (normal range, 0–166 pg/ml), whereas the level of cTnI was 0.01 ng/ml (normal range, 0–0.07 ng/ml). Clinical and laboratory examinations also revealed: normocytic anemia (Hb 10.8 g/dl, MCV 82 fl), white blood cell count 10000/mm with normal differential count, platelet count 392000/mm, low serum protein level 4.4 g/dl, hypoalbuminemia 2.5 g/dl, 10.3% gamma-globulin, low serum IgG, IgA and IgM levels, beta2-microglobulin level increased to 4.5 mg/l (normal range, 0.8–2 mg/l), ESR 38 mm. Skeletal X-ray examination detected three osteolytic lesions in the skull. Tongue enlargement with…
International Journal of Clinical & Laboratory Research, Dec 1, 1993
The high frequency of liver involvement in cryoglobulinemia is well established. Although both et... more The high frequency of liver involvement in cryoglobulinemia is well established. Although both etiology and pathogenesis have remained so far undefined, recent studies suggest an association of mixed cryoglobulinemia with hepatitis C virus infection. To explore this hypothesis further, we assessed the prevalence of hepatitis C virus antibodies and RNA in a large group of patients, including: (1) 35 patients with cryoglobulinemia without clinical evidence of liver involvement (group 1), (2) 15 patients with symptomatic cryoglobulinemia associated with chronic liver disease (group 2) and (3) 12 patients with asymptomatic cryoglobulinemia associated with chronic liver disease (group 3). Anti-hepatitis C virus antibodies were detected by a second-generation enzyme-linked immunosorbent assay and third-generation immunoblot (SIA Prototype RIBA), whereas the polymerase chain reaction was used for the detection of viral RNA. Anti-hepatitis C virus antibodies, as detected by enzyme-linked immunosorbent assay, were demonstrated in 21 (60%) patients from group 1, 11 (73.3%) from group 2 and 10 (83.3%) from group 3. The immunoblot identified as positive 3 further patients in group 1 (giving a prevalence of 68.6%) and all patients in groups 2 and 3. Hepatitis C virus RNA was demonstrated in cryoprecipitates from 21 of 24 immunoblot-positives and from 6 of 11 immunoblot-negatives, indicating an actual active viral replication in 77.1% of group 1. This was also found in 13 (86.7%) and 10 (83.3%) cryoprecipitates of groups 2 and 3, respectively. Type II cryoglobulinemia was the prevalent form in group 1 (88.6%) and group 2 (73.3%), whereas type III was found in group 3 (58.3%) and in 26.7% of group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monot... more 6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monotherapy over 6 months, showed 47% overall response rate (ORR) in patients (pts) with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab (FA-ref), or to fludarabine with bulky (>5cm) lymphadenopathy (BF-ref). The effects of ofa retreatment (retx) and maintenance (mt) are unknown. Methods: Pts who responded to ofa and then progressed or had stable disease (SD) in Study 406, were offered retx in Study 416 (NCT00802737; GSK/Genmab) with ofa 1 x 300 mg + 7 x 2000 mg weekly followed by mt with ofa 2000 mg monthly for up to 2 years (if SD or better). Primary endpoint was ORR (1996 NCI-WG). Safety and time to event outcomes were also assessed. Results: Of 29 pts enrolled, 7 had SD and 22 had partial response (PR) and progressed in Study 406. Pts were defined per Study 406: 17 FA-ref, 11 BF-ref, 1 “other”. Pretreatment characteristics were similar between groups. Pts received a median of 12 doses (range 3-32); 86% had 8 doses, 3% received all 32 doses. 72% of pts had infusion-related adverse events (AEs), 41% at 1st infusion, mostly grade 1-2. The most common grade >3 AE occurring up to 60 days after last tx was infection (38%); the most common was pneumonia (17%). 3 pts (10%) had fatal infections, all bronchopneumonia. Clinical efficacy is shown in Table. Comparative analysis to Study 406 is ongoing. Conclusions: The response to ofatumumab (ofa) as induction retreatment and progression-free survival in this limited number of pts was similar to 1st treatment (Study 406). Ofa maintenance had some clinical benefit for pts with advanced CLL. Ofa was well-tolerated with no unexpected toxicities. [Table: see text]
Abstract 3020 Background. In patients with newly diagnosed MM, three/four-drug combinations seem ... more Abstract 3020 Background. In patients with newly diagnosed MM, three/four-drug combinations seem to be more effective compared with two-drug associations in terms of both rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) are still unknown. Methods. This is a multicenter, phase II study including patients with r-rMM having measurable disease, no more than 4 prior lines of therapy, adequate performance status, cardiac and liver function. As induction therapy patients received 6 28-day cycles of oral thalidomide 100 mg/day continuously at bedtime, oral dexamethasone 20 mg on day 1–2, 4–5, 8–9, 11–12, pegylated Liposomal Doxorubicin (pLD) 30 mg/m2 iv on day 4 and bortezomib 1.3 mg/m2 iv on day 1, 4, 8, 11 (ThaDD-V). As consolidation patients underwent 6 28-day cycles of rotating bortezomib 1.3 mg/m2 iv on day 1, 4, 8, 11 plus oral dexamethasone 20 mg on day 1–2, 4–5, 8–9 (3 courses) or thalidomide 100 mg/day continuously at bedtime plus oral dexamethasone 20 mg on day 1–4 (3 courses). Patients eligible and having suitable stem cell storage underwent ASCT instead of standard consolidation at the discretion of attending physician. Maintenance therapy included thalidomide 100 mg/day until relapse or intolerable toxicity. Since in the first 20 patients we recognized an excess of peripheral neuropathy, protocol was amended as follow: bortezomib 1.3 mg/m2 on day 1, 4, 11 and thalidomide 50 mg/day in all therapeutic phases. The primary end-points of this study were best response and toxicity of the planned therapy. Results. Forty-six patients were enrolled. Median age was 63.5 years (range 31–80 years) and the median number of prior regimens was 1 (range 1–4). Twenty-four patients (52%) had undergone autologous stem cell transplantation, 30 (65%) had received anthracyclines, 27 (59%) thalidomide, 8 (17.5%) bortezomib and 16 (35%) were refractory to the last regimen. After induction 16 patients (34.5%) achieved CR (6=13% sCR), 15 (32.5%) VGPR and 4 (8.5%) PR with a ORR of 76.5%. Seven patients (15%) progressed. Out of 46 patients undergone induction, 26 (20 standard, 6 ASCT) received consolidation therapy since 1 patients died during induction, 8 had progressive disease, 1 had second neoplasm, 7 had severe toxicities and 3 undergone allogeneic stem cell transplantation. Excluding 6 patients who have obtained sCR before, 5 (25%) out of 20 patients had further improvement in response. Therefore, best response after induction and consolidation were: 25 CR (54%; 8 sCR=17.5%), 16 VGPR (34.5%) and 2 PR (4.5%). Maintenance therapy did not further improve response. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p= 0.010) whereas prior ASCT, thalidomide or bortezomib, refractory disease and bortezomib dose-intensity did not affect quality of response. After a median follow-up of 31 months (range 12–53), 28 patients relapsed and 20 died. Median TTP was 18.5 months, median PFS was 17.5 months and median survival was 40 months. Median TTP of patients achieving PR-VGPR was 16 months (3 years= 10%) whereas in those obtaining CR it was 32.5 months (3 years= 45%; p=0.032) vs not reached (3 years= 85%) in patients achieving sCR (p=0.003). Main toxicity was peripheral neuropathy (PN). Indeed, in the first 20 patients we observed 6 (30%) grade 2 and 3 (15%) grade 3 PN. After amendment, grade 2 and 3 PN occurred in 3 (11.5%) and 2 patients (7.5%), respectively. DVT occurred in 2 patients (4.5%) and severe infection in 7 (15%). Grade 3–4 neutropenia, anemia and thrombocytopenia occurred in 4 (8.5%), 2 (4%) and 7 patients (15%), respectively. Finally, only one patients died of myocardial infarction during induction. During consolidation therapy other 2 patients developed grade 3 peripheral neuropathy. During maintenance with thalidomide no patients developed severe neuropathy requiring discontinuation. Conclusions. Multi-drug combination namely ThaDD-V as induction followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses are still possible. A reduced dose-intensity of bortezomib significantly decreases PN without jeopardizing outcome. Disclosures: Offidani: Celcene, Janssen Cilag: Honoraria. Polloni:Celgene: Honoraria. Corvatta:Celgene: Honoraria. Gentili:Celgene: Honoraria. Brunori:Celgene, Janssen-Cilag: Honoraria. Catarini:Cerlgene, Janssen-Cilag: Honoraria. Malerba:celgene, Janssen-Cilag: Honoraria. Leoni:Celgene, Janssen-Cilag: Honoraria.
Quantitative measurements of circulating free immunoglobulin light chains (FLC) and of biomarkers... more Quantitative measurements of circulating free immunoglobulin light chains (FLC) and of biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins (cTnT and cTnI) are the expression of recent diagnostic and prognostic advances in AL amyloidosis. Here, we report a patient diagnosed as having AL amyloidosis involving heart, kidney and soft tissue, in association with immunoglobulin D multiple myeloma (MM). This is an extremely rare disease, mostly associated with a poor prognosis. In our patient, the front-line therapy with thalidomide and dexamethasonewasearly discontinued becauseof toxicity,whereas thesecond-line therapywith melphalan and dexamethasone produced complete hematological response and improvement in the involved organs, still maintained after a 3.10 year followup. Circulating FLC, NT-ProBNP and cTnI were measured in the context of diagnostic and monitoring assessments, demonstrating a significant progressive reduction of lambda FLC and NT-ProBNP that could be related to the treatment response and long survival. Introduction: AL amyloidosis, characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissue, mostly occurs in association with a plasma cell dyscrasia. IgD multiple myeloma (MM) is an extremely rare disease, accounting for 2% of all MM cases in which AL amyloidosis, Bence-Jones lambda light chain proteinuria and renal function impairment appear to be particularly frequent [1]. The pathological light chains, responsible for the organ dysfunction in patients with AL amyloidosis, can be estimated by measuring circulating biomarkers. In particular, determining serum levels of free Ig light chains (FLC) improves diagnosis and it is a powerful tool for assessment of treatment response and as predictor of prognosis [2]. In the patients with cardiac involvement, circulating levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and cardiac troponins (cTnT and cTnI) are highly specific markers of myocardial injury, and changes in their concentrations following treatment provide prognostic informations [3,4]. Here, we describe the clinical and laboratory findings of a 61-year-old woman, referred in 2006 to the nephrology clinic because of nephrotic-range proteinuria (24-hr urinary protein 3.96 g/dl), serum creatinine 0.7 mg/dl and creatinine clearance 48 ml/min. Her medical history included carpal tunnel syndrome at her right hand (for which she had undergone surgery 6 months before) and arterial hypertension since 1993. Our aim was to show the diagnostic and prognostic relevance of circulating FLC and cardiac biomarkers in AL amyloidosis. Methods: Our patient was investigated for suspicion of AL amyloidosis. Diagnostic work-up and prognostic evaluation included renal and bone marrow (BM) biopsies, serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), immunonephelometric Ig serum FLC immunoassay (FREELITE, The Binding Site Ltd, Birmingham, UK), 24h-urine electrophoresis (UPE), urine IFE, beta2-microglobulin, and determination of cardiac biomarker levels (i.e. NT-proBNP and cTnI). Results and discussion: Renal biopsy demonstrated homogeneous mesangial and sub-endothelial AL amyloid deposition, producing apple-green birifrangence under polarized light when stained with Congo-red dye; immunofluorescence showed bright staining for lambda light chain. SPE disclosed a monoclonal band (0.27 g/ dl) in the beta region, that on IFE resulted in IgD isotype with lambda light chain restriction. Bence-Jones proteinuria of lambda type was demonstrated by UPE. BM biopsy disclosed 50% infiltration by plasma cells with lambda chain restriction, exhibiting cytoplasmic azurophilic granules. Serum lambda FLC were increased to 9.4 mg/dl (normal range, 0.5–2.6 mg/dl), whereas kappa FLC were 0.8 mg/dl (normal range, 0.3–1.9 mg/dl). Fine-needle aspiration of abdominal fat did not result diagnostic. Electrocardiography showed the presence of low voltage in all limb leads; echocardiography revealed ‘ground glass’ appearance, interventricular septal thickness 17 mm, wall thickness 12 mm, and left ventricular 45% EF; doppler echocardiography detected evidence of grade II diastolic dysfunction; holter-ECG did not show complex ventricular arrhythmias. The serum concentration of NT-ProBNP was increased to 3096 pg/ml (normal range, 0–166 pg/ml), whereas the level of cTnI was 0.01 ng/ml (normal range, 0–0.07 ng/ml). Clinical and laboratory examinations also revealed: normocytic anemia (Hb 10.8 g/dl, MCV 82 fl), white blood cell count 10000/mm with normal differential count, platelet count 392000/mm, low serum protein level 4.4 g/dl, hypoalbuminemia 2.5 g/dl, 10.3% gamma-globulin, low serum IgG, IgA and IgM levels, beta2-microglobulin level increased to 4.5 mg/l (normal range, 0.8–2 mg/l), ESR 38 mm. Skeletal X-ray examination detected three osteolytic lesions in the skull. Tongue enlargement with…
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