melphalan and Nephrotic-Syndrome

An eighty-one-year-old male with lower leg edema and proteinuria was diagnosed as having nephrotic syndrome and was hospitalized for a detailed examination. Kidney biopsy and immunostaining revealed nodular glomerulosclerosis and deposition of lambda chains, respectively. Because these findings indicate the occurrence of light chain deposition disease (LCDD), the underlying disease was found to be multiple myeloma BJ-lambda. After the administration of melphalan and prednisolone, followed by further addition of zoledronic acid, the patient's nephrosis remitted. However, renal dysfunction gradually deteriorated further and hemodialysis was instituted. He eventually died of gastrointestinal bleeding and biliary infection. The period of time from the initial diagnosis to death was thirty months. Autopsy revealed pervasive infiltration of plasma cells and light chain deposition in multiple organs. The uncontrollable gastrointestinal bleeding appears to have been caused by light chain deposition in the vascular walls of a bile duct. Although medical treatment for elderly LCDD cases depends on chemotherapy alone, it is difficult to obtain a complete remission with melphalan and prednisolone, according to the literature. Reports on the validities of biological agents, such as bortezomib, are beginning to appear, and accumulation of further therapeutic experience is eagerly awaited.

Topics: Aged, 80 and over; Autopsy; Humans; Immunoglobulin Light Chains; Kidney; Male; Melphalan; Microscopy, Electron; Multiple Myeloma; Nephrotic Syndrome; Prednisolone

Light chain deposition disease (LCDD) damages most frequently kidneys, and less frequently other organs. The incidence of LCDD is lower than the incidence of AL-amyloidosis. Symmetric swelling of both legs was the first sign of nephrotic syndrome with renal insufficiency in our female patient. Renal biopsy specimen revealed the diagnosis of LCDD. Bone marrow biopsy contained 40% of plasma cells. Bone survey showed no osteolytic changes. These findings confirmed the diagnosis of multiple myeloma (MM) Durie Salmon stage IB with LCDD. The patient was initially treated with 4 cycles of VAD (vinkristine, adriamycine, dexamethasone) chemotherapy with no response. Followed collection of peripheral haematopoietic stem cells and later high dose chemotherapy with reduced dose of melphalan 140 mg/sqm and autologous peripheral haematopoietic stem cells transplantation. Melphalan dose was reduced because of renal insufficiency (serum creatinine 290 micromol/l) before application of conditioning regimen. High dose therapy was complicated by with deterioration of renal function, creatinine increased to 600 micromol/l. Worsening of renal function was most likely caused by nephrotoxicity of melphalan in nephrotic syndrome. This has been previously described in patients with AL-amyloidosis, and nephrotic syndrome who were treated with high dose melphalan. This phenomenon was entitled "post conditioning renal insufficiency". Hypoalbuminemia hypoproteinemia and reduced intravascular volume and renal damage caused by amyloid deposits as well as probably, amorphous non-amyloid deposits of monoclonal immunoglobulin are likely to have contributed to nephrotoxicity of the high dose of melphalan. However, worsening of renal insufficiency was facilitated by the mucositis-associated sepsis. Follow-up examination one month after high dose chemotherapy showed complete remission, that was confirmed by further examinations. In the course of the first year after high dose chemotherapy renal function gradually improved and nephrotic syndrome completely disappeared (complete kidney remission). Proteinuria declined to 2-3 g/24 hours and glomerular filtration slowly improved. Three years after high dose chemotherapy the patient is still in complete remission of multiple myeloma and free of nephrotic syndrome, with slightly increased creatinine (160 micromol/l) that, nevertheless, has had an improving tendency over last 3 years. The present case study illustrates accomplishment of complete ha

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Kidney; Melphalan; Multiple Myeloma; Nephrotic Syndrome; Remission Induction; Transplantation, Autologous

Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Alkylating Agents; Amyloidosis; Boston; Cardiomyopathies; Case Management; Clinical Trials as Topic; Combined Modality Therapy; Factor X Deficiency; Female; Forecasting; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Male; Melphalan; Middle Aged; Multicenter Studies as Topic; Multiple Organ Failure; Nephrotic Syndrome; Patient Care Team; Patient Selection; Pilot Projects; Remission Induction; Renal Dialysis; Survival Analysis; Survival Rate; Transplantation Conditioning; Treatment Outcome

Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk. The hallmark of this syndrome is proteinuria greater than 3.5 grams per 24 hours, and the clinical features are secondary manifestations of an underlying primary glomerular or systemic disease. The objectives of treatment are threefold: correcting the primary disease, decreasing the symptoms and secondary effects associated with this syndrome, and preventing complications. This article presents a case report of a man diagnosed with nephrotic syndrome secondary to amyloidosis. The clinical aspects of the disease processes, the diagnostic evaluation, the treatment course, and disease management are discussed.

Topics: Adult; Amyloidosis; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Biopsy; Combined Modality Therapy; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Male; Medical History Taking; Melphalan; Nephrotic Syndrome; Physical Examination; Prednisone; Referral and Consultation

This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis (AL). Twenty-three patients had stem cells collected between November 1995 and September 1998. Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4. Three patients did not undergo stem cell infusion because of poor performance status. Two died of progressive amyloid at 1 and 3 months. One patient is alive on hemodialysis. Fourteen males and six females (median age, 57 years) underwent transplantation. Renal, cardiac (by echocardiography), peripheral neuropathy or liver amyloidosis occurred in 14, 12, 3, and 1, respectively. Echocardiography demonstrated an interventricular septal thickness > or = 15 mm in six patients, five of whom died post transplantation. Three patients died of progressive amyloidosis at 7, 7, and 21 months. Thirteen patients are alive with a follow-up of 3 to 26 months. Twelve (60%) fulfilled the criteria of a hematologic or organ response. Severe gastrointestinal tract toxicity was seen in five (25%). We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma. The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease.

Topics: Adult; Aged; Amyloidosis; Arrhythmias, Cardiac; Disease Progression; Female; Follow-Up Studies; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Liver; Male; Melphalan; Middle Aged; Myocardium; Nephrotic Syndrome; Peripheral Nervous System Diseases; Radiation Injuries; Renal Dialysis; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation

The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 years from the time of diagnosis with current management approaches. Clearly, more effective therapies are needed for this rapidly lethal disease. Five patients were treated with dose-intensive melphalan and blood stem cell support and followed for a period of 1 year. Patients were diagnosed with AL amyloidosis by tissue biopsy and categorized by performance status and organ involvement. Their plasma cell dyscrasias were evaluated with immunofixation electrophoresis of serum and urine specimens, quantitative serum lgs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor-mobilized blood stem cells, clinical evaluations and plasma cell studies were repeated at 3 and 12 months. Three men and 2 women aged 38 to 53 years were treated. Median performance status (SWOG) was 2 (1 to 3), and clinical presentations included nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatomegaly (n = 1). With a median follow-up of 13 months (12 to 17 months), all five patients are well and have shown stable or improved performance status and clinical remission of organ-related dysfunction, including a 50% reduction in daily proteinuria with no change in creatinine, reversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of the 5 patients (60%) at 12 months after treatment, plasma cell dyscrasias could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feasible therapy for patients with AL amyloidosis, even when there is clinical evidence of cardiac involvement. At least some patients with AL amyloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-specific disease after this form of treatment.

Topics: Adult; Amyloidosis; Cardiomyopathies; Feasibility Studies; Female; Follow-Up Studies; Gastrointestinal Diseases; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hepatomegaly; Humans; Karnofsky Performance Status; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Neutropenia; Peripheral Nervous System Diseases; Prednisone; Remission Induction; Treatment Outcome

We report a 58-year-old Japanese woman who presented with nephrotic syndrome. Steroid therapy and cyclosporine A administration were initiated, but hematological remission and renal response were not achieved. Renal biopsy revealed amyloid deposits in the mesangial region and the small arteries. Proteomic analysis based on laser microdissection and mass spectrometry showed that the amyloid deposits were composed of the constant region of the lambda light chain. She received vincristine, adriamycin, and dexamethasone therapy followed by high-dose melphalan and autologous stem cell transplantation, resulting in hematological complete remission and renal response with negative urinary Bence-Jones protein and proteinuria. Renal biopsy was performed four times during follow-up, demonstrating that amyloid deposits decreased gradually, while glomeruli showing global sclerosis increased from 3 to 62%. This case suggests that glomerular amyloid deposits can be cleared via tissue remodeling, if stem cells producing amyloid precursors are completely replaced by unrelated cells after stem cell transplantation.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Asian People; Combined Modality Therapy; Dexamethasone; Doxorubicin; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin lambda-Chains; Immunoglobulin Light-chain Amyloidosis; Kidney; Melphalan; Middle Aged; Myeloablative Agonists; Nephrotic Syndrome; Plaque, Amyloid; Proteomics; Remission Induction; Transplantation, Autologous; Vincristine

To investigate the clinical characteristics and histopathological features of kidney disease in elderly patients.. We retrospectively analyzed the results of 4,185 consecutive renal biopsies, and 288 patients aged >60 years at the Second Hospital of Jilin University from January 1998 to December 2013 were finally included. All patients had been clinically and histologically diagnosed with kidney disease.. Nephrotic syndrome was the main clinical indication for biopsy. Twenty-four patients (8.33 %) experienced a minor complication related to their biopsy procedure. Among patients diagnosed as primary glomerulonephritis (GN), membranous nephropathy (MN) was the most frequent subclassification (24.7 %), followed by mesangioproliferative glomerulonephritis (MsPGN, 11.1 %) and IgA nephropathy (IgAN, 8.0 %). Amyloidosis (8.7 %) was the most common secondary GN, followed by antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune GN (5.2 %) and diabetic nephropathy (DN, 3.8 %). Based on renal biopsies results, 143/288 patients received immunosuppressive therapy and showed an overall remission rate (complete plus partial remissions) of 74.1 %. Among 71 MN patients, 29 patients received steroids plus cyclophosphamide and showed a remission rate of 79.3 %, while 42 patients received steroids and tacrolimus and showed a remission rate of 90.5 %. Among 25 patients with amyloidosis, 22 cases received melphalan plus dexamethasone and showed a remission rate of 40.9 %, while three patients received vincristine, adriamycin, and dexamethasone and showed a remission rate of 66.7 %.. Making an accurate pathologic diagnosis by renal biopsy is crucial for selecting the proper treatment for elderly patients with kidney disease.

Topics: Aged; Aged, 80 and over; Amyloidosis; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antineoplastic Agents, Alkylating; Autoimmune Diseases; Biopsy; Cyclophosphamide; Dexamethasone; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Retrospective Studies; Tacrolimus; Treatment Outcome

We report a 50-year-old female patient with diffuse and rapidly progressing splenic calcification. She had developed nephrotic syndrome and been diagnosed with renal amyloid light-chain amyloidosis in 2010. Although she had been given melphalan and dexamethasone therapy and high-dose melphalan followed by autologous blood stem-cell transplantation, her renal function worsened and hemodialysis was started in May 2011. Since November 2011, splenic calcification, probably associated with amyloidosis, had progressed, and diffuse calcification was observed throughout the splenic area in September 2012. During the same period, the patient was hospitalized for thrombocytopenia. Although splenic dysfunction due to calcification was suspected to be the cause of thrombocytopenia, the association between the two could not be established. The platelet count rose with an improvement in hepatic congestion due to reinforced fluid removal during dialysis.

Topics: Amyloidosis; Calcinosis; Dexamethasone; Disease Progression; Female; Humans; Melphalan; Middle Aged; Nephrotic Syndrome; Peripheral Blood Stem Cell Transplantation; Renal Insufficiency; Splenic Diseases; Thrombocytopenia; Transplantation, Autologous

An atypical case of late-onset lattice corneal dystrophy is described in a 61-year-old man without a family history of eye disease. Mutational analysis of the TGFBI gene excluded any pathogenic sequence variants. However, 2 years later, renal impairment and nephrotic syndrome were diagnosed, resulting in a diagnosis of systemic heavy-chain amyloidosis.. Slit-lamp examination, corneal photography, and in vivo confocal microscopy were performed. General systemic evaluation included blood and urine assessment, bone marrow and renal biopsies, and cardiologic evaluation. A DNA sample underwent initial mutational analysis of TGFBI and, subsequently, gelsolin. The renal biopsy sample was subject to direct protein sequencing by mass spectrometry.. A bilateral, atypical, fine, midperipheral lattice corneal dystrophy with minor central subepithelial scarring was clinically characterized. Subsequently, abnormal renal functions with proteinuria, IgG lambda paraproteinemia, extensive deposition of amyloid in renal glomeruli, and increased plasma cells in bone marrow were identified. No pathogenic sequence mutations were identified in TGFBI or the gelsolin genes. Direct protein sequencing by mass spectrometry showed amyloid to be heavy-chain deposition rather than the more usual light-chain deposition.. Atypical midperipheral lattice corneal dystrophy presenting with adult onset and negative family history should arouse suspicion for an association with paraproteinemias or amyloidosis. Exclusion of TGFBI mutations should alert the clinician to the possibility of potentially life-threatening conditions, with referral for careful systemic evaluation.

Topics: Amyloid; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Corneal Dystrophies, Hereditary; Dexamethasone; DNA Mutational Analysis; Extracellular Matrix Proteins; Gelsolin; Glucocorticoids; Humans; Immunoglobulin Heavy Chains; Male; Mass Spectrometry; Melphalan; Microscopy, Confocal; Middle Aged; Mutation; Nephrotic Syndrome; Paraproteinemias; Pyrazines; Sequence Analysis, Protein; Transforming Growth Factor beta

Topics: Amyloid; Amyloidosis; Antifibrinolytic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Blood Coagulation; Blood Coagulation Factors; Dexamethasone; Disseminated Intravascular Coagulation; Female; Humans; Immunoglobulin kappa-Chains; International Normalized Ratio; Melphalan; Middle Aged; Nephrotic Syndrome; Partial Thromboplastin Time; Vitamin K

A 52-year-old woman was admitted to our hospital for treatment of nephrotic syndrome. Funduscopic findings showed fundal hemorrhage and soft exudates, and serologic analysis showed a monoclonal serum component that was identified as Bence Jones protein-k type. A bone marrow biopsy showed diffuse proliferation of atypical plasma cells, while a renal biopsy showed diffuse and nodular mesangial proliferation. Immunohistochemical staining confirmed the presence of k chains along the glomerular basement membrane and in mesangial areas. The patient was diagnosed as multiple myeloma (Bence Jones k type) with light chain deposition disease (LCDD). After high-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT), the multiple myeloma and nephrotic syndrome were in complete remission; her renal function was improved, but a renal biopsy performed 6 months after PBSCT showed the persistence of diffuse and nodular lesions. By contrast, a renal biopsy performed 3 years later showed complete resolution of the diffuse and nodular mesangial proliferation.

Topics: Antineoplastic Agents, Alkylating; Bence Jones Protein; Biopsy; Female; Humans; Immunoglobulin Light Chains; Immunohistochemistry; Kidney Neoplasms; Melphalan; Mesangial Cells; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Peripheral Blood Stem Cell Transplantation; Remission Induction; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Topics: Amyloidosis; Dexamethasone; Drug Therapy, Combination; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Paraproteinemias; Peripheral Nervous System Diseases; Secondary Prevention

Refractory pleural effusions present a challenging management problem and are associated with a poor prognosis in patients with primary systemic amyloidosis (AL). We report a series of four patients with AL who presented with bilateral pleural effusions that were refractory to diuretic therapy. After treatment with bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, three of the four patients had improvement in their pleural effusions, peripheral edema, and functional status. Additional studies are needed to further define the role of bevacizumab in the management of this group of patients.

Topics: Amyloidosis; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Captopril; Chest Tubes; Combined Modality Therapy; Dexamethasone; Diuretics; Drug Resistance; Edema; Fatal Outcome; Furosemide; Humans; Hypoalbuminemia; Male; Melphalan; Metolazone; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Peripheral Blood Stem Cell Transplantation; Pleural Effusion; Prednisolone; Serum Albumin; Spironolactone; Thalidomide; Thoracostomy; Transplantation, Autologous; Vascular Endothelial Growth Factor A

Multicentric Castleman disease is a systemic lymphoproliferative disease with incomplete understood etiology. The various renal complications of this disease may include minimal change disease, mesangial proliferative glomerulonephritis, membranous glomerulonephritis and nephrotic syndrome, caused by secondary amyloidosis. In several reported cases of localized Castleman disease associated with renal amyloidosis and nephrotic syndrome, resection of organs involved by lymphoid proliferation resulted in complete remission. However, therapy of multicentric Castleman disease with renal amyloidosis is not well-established. We treated a case of a 39-year-old woman with multicentric Castleman disease complicated by nephrotic syndrome caused by secondary AA amyloidosis. The patient underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), achieving complete remission. Autologous stem cell transplantation may be an attractive choice in therapy for refractory multicentric Castleman disease.

Topics: Adult; Amyloidosis; Castleman Disease; Female; Humans; Kidney Failure, Chronic; Melphalan; Myeloablative Agonists; Nephrotic Syndrome; Peripheral Blood Stem Cell Transplantation

Cardiac involvement occurs in up to 50% of patients with primary or A amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failure patients and as an index of myocardial dysfunction in patients with ALA. Data about BNP dosage for cardiovascular monitoring of patients with ALA on renal replacement therapy are lacking.. A 64 year old Caucasian man was admitted because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given but renal function worsened and in April 2004 standard bicarbonate hemodialysis was started. In March 2004 thalidomide was added to his therapy. During the follow-up ejection fraction was stable and was 65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma levels were increased and the values recorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow-up longer than two years.. In ALA patients a powerful prognostic role of BNP has been reported whose expression is increased in ventricular myocytes of patients with cardiac involvement. BNP level monitoring does not appear to be superior to standard echocardiography in evaluating cardiovascular status of uremic patients with ALA.

Topics: Amyloidosis; Anti-Inflammatory Agents; Bicarbonates; Buffers; Cardiac Output, Low; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Nephrotic Syndrome; Prednisolone; Renal Dialysis; Thalidomide; Treatment Outcome

A 52-year-old patient with atypical plasmocytoma presented with a bilateral serous detachment of the retina as well as a huge detachment of the pigment epithelium (PE) in the periphery. Shortly thereafter the PE ruptured. In the left eye this led to substantial central macular fibrosis.. The clinically healthy patient showed a nephrotic syndrome; neither typical monoclonality was detectable nor was erythropoiesis or myelopoiesis reduced.. To avoid further reduction of VA pars plana vitrectomy (ppV) with silicone oil tamponade and laser coagulation was performed. Clinical findings were reduced significantly and VA was stabilized for 2.5 years.. PE detachments and serous retinal detachments in patients with nephrotic syndrome are only mentioned in a few cases. However, a peripheral rupture of the PE to this extent seems to be very rare. Early ppV with silicone oil and laser coagulation may prevent further macular fibrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Choroidal Neovascularization; Comorbidity; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Kidney Neoplasms; Laser Coagulation; Lenses, Intraocular; Melphalan; Middle Aged; Nephrotic Syndrome; Ophthalmoscopy; Plasmacytoma; Postoperative Complications; Prednisolone; Recurrence; Renal Insufficiency; Reoperation; Retinal Detachment; Retinal Perforations; Silicone Oils; Visual Acuity; Vitrectomy

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Carcinoma, Squamous Cell; Clarithromycin; Dexamethasone; Diphosphonates; Glomerulonephritis; Humans; Idarubicin; Imidazoles; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Pamidronate; Protein Synthesis Inhibitors; Pyrazines; Skin Neoplasms; Thalidomide; Zoledronic Acid

Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity.

Topics: Amyloidosis; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Paraproteinemias; Proteinuria; Remission Induction; Salvage Therapy; Transplantation, Homologous; Treatment Failure

Amyloidosis is a systemic disease characterized by generalized deposition of beta-organized proteic fibrillar material with green birefringence under polarized light, in different tissues and organs, the most frequent kidney, liver and heart, with important clinical repercussion. Primary or AL amyloidosis is the most common subtype of amyloidosis (1), confirmed by biopsy-proved amyloid deposition in abdominal fat pad, rectum, kidney or liver, if necessary, in which fragments of monoclonal light chains are deposited. Cases with factor X (Stuart factor) of coagulation deficiency associated are described, due to adsorption of this factor to amyloid fibrills. Normally, evolution is fatal, with only few months of survival. We report a case of primary amyloidosis with nephrotic syndrome, severe factor X deficiency (without bleeding complications), possible heart affection and short-term good response to chemotherapic treatment.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Drug Therapy, Combination; Factor X Deficiency; Glucocorticoids; Humans; Immunoglobulin lambda-Chains; Kidney; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Prednisone; Treatment Outcome

Primary AL amyloidosis involves vital organs from the early phase of illness, resulting in a poor prognosis. We report a patient with nephrotic syndrome due to this type of amyloidosis, who was successfully treated with two courses of VAD (vincristine, doxorubicin and dexamethasone) and subsequent high-dose melphalan (140 mg/m2) with autologous stem cell support. Following the serial chemotherapy his proteinuria improved, and M protein became undetectable in both serum and urine. To avoid the progression of primary AL amyloidosis, intensive chemotherapy should be actively used when the general status and vital organ functions are well preserved.

Topics: Amyloid; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Transplantation, Autologous

Topics: Acute Kidney Injury; Amyloidosis; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kidney Function Tests; Melphalan; Middle Aged; Nephrotic Syndrome; Recovery of Function; Risk Assessment; Severity of Illness Index; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

A 68-year-old man with a 30-year history of essential thrombocytosis developed nephrotic syndrome. Renal biopsy showed massive deposits of Congo red-negative periodic acid Schiff (PAS)-positive substance in the mesangium and capillary wall that was positive for IgG. Electron microscopic examination revealed 10- to 20-nm fibrils in the deposits, and there was no other organ involvement; thus, we diagnosed fibrillary glomerulonephritis. This is the first report of a case of fibrillary glomerulonephritis associated with essential thrombocytosis.

Topics: Aged; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Bone Marrow; Glomerulonephritis; Humans; Kidney; Male; Melphalan; Microscopy, Electron; Nephrotic Syndrome; Prednisolone; Thrombocytosis

Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation induces remission of the plasma cell dyscrasia in a substantial proportion of patients with AL amyloidosis. The impact of this treatment on associated renal disease is not known.. To determine the effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease.. Prospective cohort study.. Academic medical center.. 65 patients with AL amyloidosis and urinary protein excretion greater than 1 g/24 h who received dose-intensive intravenous melphalan and autologous blood stem-cell transplantation between 1 July 1994 and 30 June 1998.. 24-hour urinary protein excretion, serum cholesterol level, serum albumin level, creatinine clearance, urine and serum immunoelectrophoresis, and bone marrow biopsy. Renal response was defined as a greater than 50% reduction in urinary protein excretion in the absence of a 25% or greater reduction in creatinine clearance. Complete hematologic response was defined as absence of detectable monoclonal protein in serum and urine and a bone marrow specimen containing less than 5% plasma cells without clonal dominance of kappa or lambda isotype.. Among the 50 patients who survived for at least 12 months, proteinuria, hypoalbuminemia, and hypercholesterolemia improved during follow-up; 36% met criteria for a renal response. Median 24-hour urinary protein excretion decreased from a baseline value of 9.6 g/24 h to 1.6 g/24 h at 12 months among patients with complete hematologic response, and 71% met criteria for a renal response. Twenty-hour urinary protein excretion did not decrease during follow-up among patients with persistent plasma cell disease, and only 11% had a renal response at 12 months (P < 0.001 for hematologic responders vs. nonresponders).. Dose-intensive intravenous melphalan with autologous blood stem-cell transplantation improves the nephrotic syndrome in patients with AL amyloidosis-associated renal disease. The benefit is largely limited to patients achieving eradication of the underlying plasma cell dyscrasia.

Topics: Adult; Aged; Amyloidosis; Cholesterol; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Hypercholesterolemia; Infusions, Intravenous; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Proteinuria; Transplantation, Autologous; Treatment Outcome

Amyloidosis may be primary or myeloma-associated. Skeletal lesions and the percentage of bone marrow plasma cells (<10% in primary, >20% in myeloma) account for the major differences between the two varieties. In the literature there are rare cases of primary amyloidosis presenting without myeloma and followed by development of myelomatous manifestations. Usually, the primary disease (i.e. the myeloma) is advanced, when amyloidosis is diagnosed. We describe a patient who had presented with a severe and progressive systemic amyloidosis and was diagnosed later to have a mild light chain myeloma. Aggressive treatment with melphalan, prednisone and colchicine resulted in a temporary partial remission, followed by a rapid downhill course, and the patient's death. The point of relatively mild myeloma following a rapidly progressive course of advanced amyloidosis is emphasized. Awareness of the possibility of such a combination may lead to early diagnosis, a more aggressive or novel therapeutic approach and, possibly, to a better prognosis.

Topics: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Colchicine; Disease Progression; Fatal Outcome; Female; Heart Failure; Humans; Melphalan; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Prednisone

In a patient with nephrotic syndrome, renal biopsy revealed AL amyloid deposits. Monoclonal lambda light chains were identified in serum and urine. A low percentage of monoclonal plasma cells was detected in the bone marrow. The patient received four cycles of VAD and subsequent high-dose chemotherapy (HDCT) with melphalan (200 mg/m2) followed by autologous peripheral blood stem cell transplantation. Proteinuria rapidly diminished during chemotherapy. Three months after HDCT, the patient has no edema, and no signs of plasma cell dyscrasia are currently detectable. Using VAD before starting HDCT may improve the condition of patients with amyloidosis and reduce transplantation-related morbidity and mortality.

Topics: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dexamethasone; Doxorubicin; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Recurrence; Transplantation, Autologous; Vincristine

We report a case of a 39-year-old man with lambda-light-chain multiple myeloma, nephrotic syndrome due to lambda-light-chain deposition disease in kidneys and amyloidosis in other tissues. The patient was treated with melphalan and prednisone for 1 year. After that, he was administered interferon-alpha2b (IFN-alpha2b; 3 MU, 3 times a week) as maintenance therapy for 2 years. At present, 5 years and 6 months after the initial diagnosis, the patient receives IFN-alpha2b (3 MU, twice a week) and remains in complete haematological remission.

Topics: Adult; Amyloidosis; Antineoplastic Agents; Humans; Immunoglobulin Light Chains; Interferon-alpha; Male; Melphalan; Multiple Myeloma; Nephrotic Syndrome; Prednisone; Remission Induction; Survivors

Topics: Adult; Aged; Amyloidosis; Colchicine; Humans; Kidney; Kidney Function Tests; Male; Melphalan; Nephrotic Syndrome; Prednisone; Proteinuria

Patients (153) with biopsy-proven primary systemic amyloidosis (AL) were evaluated for their response rate to alkylating agent-based chemotherapy. Twenty-seven of the patients (18%) responded. The serum creatinine concentration had an adverse effect on response rate (P = .05). In patients with nephrotic syndrome, a normal serum creatinine value, and no echocardiographic evidence of cardiac amyloidosis, the response rate was 39% (12 of 31). Five of 34 patients with amyloid cardiomyopathy responded. Two of these five are alive 10 years after diagnosis. None of the 18 patients with amyloid peripheral neuropathy showed regression of their disease. The median time to achieve response was 11.7 months. The median survival of the 27 patients was 89.4 months and 21 of 27 survived 5 years (78%). Eight patients remain alive with a minimum follow-up of 90 months. Seven died of acute leukemia or dysmyelopoietic syndrome, a presumed complication of melphalan therapy. In the group of 126 patients who showed no response to alkylating agent-based therapy, the median survival was 14.7 months and 9 (7%) survived over 5 years. All 126 patients have died. Alkylating agent-based chemotherapy for AL is beneficial in a subset of patients and a trial of chemotherapy is strongly recommended. Those patients who do respond demonstrate survival benefit.

Topics: Amyloidosis; Discriminant Analysis; Humans; Melphalan; Multivariate Analysis; Nephrotic Syndrome; Prednisone; Survival Analysis; Time Factors

A 45-year-old man with primary amyloidosis was initially seen with nephrotic syndrome. Factor X was found to be 5% and antithrombin III (AT III) 45% of normal plasma values. During an 11-month period, despite severe factor X deficiency, the patient did not have any bleeding complications. He developed progressive renal failure and AT III levels increased to normal, at which time he developed severe bleeding complications. These findings suggest a protective role of AT III deficiency against bleeding in a patient with severe factor X deficiency.

Topics: Amyloidosis; Antithrombin III Deficiency; Biopsy; Blood Coagulation Tests; Colchicine; Factor X Deficiency; Gastrointestinal Hemorrhage; Humans; Hypoprothrombinemias; Kidney; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Prednisone; Splenectomy

An asymptomatic multiple myeloma of the kappa-light chain type was found in a patient with nephrotic syndrome and renal insufficiency. Light microscopy showed nodular glomerulosclerosis of the kidney similar to diabetic glomerulosclerosis. Diabetes mellitus could not be demonstrated. kappa-Light chain deposits could be shown by immunohistology in the mesangium and the glomerular and tubular basal membrane. In addition, massive kappa-light chain deposits in the sinusoidal walls of the liver and at the dermoepidermal junction of the skin and in the corium were found.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Bone Marrow Cells; Carmustine; Cyclophosphamide; Humans; Hypergammaglobulinemia; Hypertension, Renal; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Plasma Cells; Plasmacytoma; Prednisone; Vincristine

We describe two patients with primary systemic amyloidosis (AL) and the nephrotic syndrome. The administration of melphalan and prednisone was associated with resolution of the nephrotic syndrome. The serum albumin level returned to normal, proteinuria decreased to near normal, edema resolved, and the monoclonal protein in the serum and urine disappeared. In both patients, renal function remained stable and hepatomegaly disappeared. In both, however, amyloid deposition was greater in follow-up renal tissue than in the initial specimen. The effect of systemic therapy in AL must be assessed with histologic observations as well as clinical indexes.

Topics: Adult; Amyloid; Amyloidosis; Female; Humans; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Prednisone

The appearance of amyloidosis during the course of multiple myeloma is a well known fact and has an overall incidence of 6 to 15%. However, the total transformation of a plasmocytoma into a voluminous amyloid tumor is a very rare event. A female patient was diagnosed of lambda light chain disease after developing a conspicuous rib plasmocytoma over the same region where a pathological fracture had appeared three years before. She was treated with discontinuous courses of melphalan and methyl-prednisolone, and developed a reversible nephrotic syndrome and a pathological fracture of the right clavicle. At necropsy there was generalized amyloidosis and complete substitution of the rib plasmocytoma by amyloid substance, with another important accumulation of amyloid in the region of the clavicular fracture. The present concepts on amyloidogenesis in multiple myeloma are reviewed, and the peculiarities of the present case together with the possible role of initiating factors and the effects of therapy are discussed. The case herein reported appears to represent a human model of focal amyloidogenesis in myeloma.

Topics: Aged; Amyloidosis; Clavicle; Female; Fractures, Spontaneous; Humans; Melphalan; Methylprednisolone; Nephrotic Syndrome; Plasmacytoma; Ribs

Two patients with progressive primary amyloidosis, monoclonal serum and urinary proteins, multiple organ involvement, and nephrotic syndrome were treated with melphalan and prednisone for one year. In one patient, splenomegaly and nephrotic syndrome rapidly responded to therapy but massive hepatomegaly responded slowly, requiring 15 months' time for normalization of size. Results of liver function tests, although improved, remained abnormal, and amyloid deposits remained in the marrow. A second patient also demonstrated dramatic diminution in proteinuria and improvement in liver function abnormalities, but macroglossia persisted. These observations suggest that amyloid organ involvement may be reversible with differences in organ responsiveness to chemotherapy. An empirical trial of chemotherapy may be indicated in some patients with progressive primary amyloidosis, and therapy may need to be continued for a prolonged period of time before seeing an effect.

Topics: Amyloidosis; Colchicine; Drug Therapy, Combination; Female; Hepatomegaly; Humans; Melphalan; Middle Aged; Nephrotic Syndrome; Prednisone; Splenomegaly

A patient with primary amyloidosis with evidence for a plasma cell dyscrasia but no abnormal immunoglobulin components had nephrotic syndrome with severe renal impairment. Kidney and bone marrow had extensive amyloid infiltration. She was treated with penicillamine, malphalan, prednisone, and fluoxymesterone; through 6 months renal function gradually improved; urine protein excretion dropped dramatically, serum albumin rose; liver size decreased; the bone marrow returned towards normal. During the next 4 1/2 years melphalan, prednisone, and fluoxymesterone treatment was continued with further improvement in renal function to normal levels. The morphologic characteristics and cellular relations of amyloid fibrils in the bone marrow were studied before, during, and after successful chemotherapy; the findings are evidence for a dual role for the reticuloendothelial cell in the formation and destruction of primary amyloidosis. This patient's response suggests that a multi-agent chemotherapy approach should be further studied.

Topics: Adult; Amyloidosis; Biopsy; Bone Marrow; Bone Marrow Cells; Female; Fluoxymesterone; Humans; Kidney Glomerulus; Melphalan; Microscopy, Electron; Nephrotic Syndrome; Penicillamine; Phagocytosis; Prednisone; Remission, Spontaneous