melphalan and Paraproteinemias

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Topics: Amyloidosis; Congo Red; Frailty; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Paraproteinemias

Fibrogenesis imperfecta ossium (FIO) is an extremely uncommon fatal bone disorder of poorly understood etiology. The pathogenesis of FIO is not well known. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. FIO clinically manifests in middle-aged adults presenting with fracture and bone pain. Elevated serum alkaline phosphatase is the only and the most consistent biochemical abnormality. Although paraproteinemia is observed in one-third of cases, the pathogenic link to the disease process is unclear. Limited information on FIO and its close resemblance to many metabolic bone disorders leads to delayed or missed diagnoses and management. Prednisolone, bisphosphonates, melphalan and steroids have been tried previously with variable success. Recently, a trial of recombinant growth hormone therapy was found to be effective. Further research focused on the pathogenetic mechanisms of FIO is needed to identify and develop targeted therapeutic options.

Topics: Alkaline Phosphatase; Biopsy; Bone and Bones; Bone Diseases, Metabolic; Collagen; Diphosphonates; Disease Progression; Fractures, Bone; Humans; Melphalan; Mutation; Osteogenesis Imperfecta; Paraproteinemias; Prednisolone; Prognosis; Radionuclide Imaging; Steroids

The monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an "onco-nephrologic" approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Bortezomib; Cyclophosphamide; Dexamethasone; Humans; Immunoglobulins; Immunosuppressive Agents; Kidney Diseases; Lenalidomide; Melphalan; Oligopeptides; Paraproteinemias; Pentostatin; Rituximab; Thalidomide; Vidarabine

Various renal disorders are associated with monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass myeloma and is recognized after electrophoretic analysis of proteinuria and AL amyloidosis, which diagnosis is usually made after pathological examination of non-invasive tissue specimens (i.e. abdominal fat or minor salivary glands), a kidney biopsy is required to identify the other types of renal disorders associated with monoclonal gammopathies and to estimate renal prognosis. Renal pathological diagnosis is difficult and relies on careful examination of kidney biopsy samples, by light microscopy, immunofluorescence studies using conjugates specific for Ig light and heavy chains, IgG sub-classes and heavy chain constant domains and by electron microscopy. In some cases, additional studies are required to identify the nature of deposits, such as immuno-electron microscopy or mass spectrometric-based proteomic analysis after laser dissection. In patients with renal disorders related to Ig light chain precipitation or deposition (myeloma cast nephropathy, AL amyloidosis, Randall-type light chain deposition disease), measurement of serum free light chains at baseline and throughout follow-up is mandatory to evaluate clonal response to chemotherapy. A more than or equal to 50% decrease in serum free light chain levels is associated with increased renal and patient survival. In AL amyloidosis, serum levels of markers of cardiac disease (NT-proBNP and troponin) are also closely associated with prognosis. Efficient chemotherapy, tailored to the underlying plasma cell or lymphoproliferative disorder and adapted to renal function, should be promptly introduced, even in the absence of overt malignant haematological disease. Renal prognosis and patient survival (particularly in AL amyloidosis and cast nephropathy) are closely associated with the rapid achievement of an haematological response. The combi

Topics: Amyloidosis; Biopsy; Boronic Acids; Bortezomib; Dexamethasone; Heart Transplantation; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Kidney; Kidney Diseases; Kidney Transplantation; Melphalan; Paraproteinemias; Plasma Exchange; Pyrazines

Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG) IgGλ or IgAλ at a low rate and systemic manifestations. They are invalidating and life-threatening.. AL-PN usually mimics small fiber length-dependent axonal polyneuropathies, but also multifocal or painful neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm the diagnosis of AL-PN, initial investigations should identify amyloidosis on nerve or accessory salivary glands, to establish the type of amyloid after serum free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is based on the presence of four criteria proposed by Dispenzieri. These neuropathies are associated with biomarkers, useful for diagnosis and treatment monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS).. Early diagnosis of these neuropathies and early treatment using high-dose melphalan associated with an autologous hematopoietic stem cell graft or low monthly doses can improve the clinical manifestations and patient survival.. Systematic search for monoclonal gammopathy by immunofixation and serum free light chains is very useful for the management of progressive peripheral neuropathies of unknown origin.

Topics: Amyloid; Amyloid Neuropathies; Biomarkers; Biopsy; Castleman Disease; Combined Modality Therapy; Drug Therapy, Combination; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin lambda-Chains; Melphalan; Paraproteinemias; Peripheral Nerves; POEMS Syndrome; Prednisone; Salivary Glands, Minor; Skin; Thalidomide; Vascular Endothelial Growth Factor A

Systemic AL amyloidosis is a rare complication of monoclonal gammopathies. Renal manifestations are frequent, mostly characterized by heavy proteinuria, with nephrotic syndrome and renal failure in more than half of the patients at diagnosis. Without treatment, median survival does not exceed 12 months. Amyloid heart disease and diffusion of amyloid deposits are associated with reduced survival. Treatment of systemic AL amyloidosis has been profoundly modified with the introduction of international criteria for the definition of organ involvement and hematologic response, and with the use of sensitive tests for the measurement of serum-free light chain levels. Melphalan plus dexamethasone is now established as the gold standard for first line treatment of systemic AL, with similar efficacy and reduced treatment-related mortality compared to high-dose therapy. Modern chemotherapy regimens, based on the use of novel agents such as bortezomib and lenalidomide, might further improve patient survival.

Topics: Amyloid; Amyloidosis; Biomarkers; Boronic Acids; Bortezomib; Cardiomyopathies; Consensus Development Conferences as Topic; Dexamethasone; Drug Therapy, Combination; Heart Transplantation; Humans; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Transplantation; Lenalidomide; Melphalan; Natriuretic Peptide, Brain; Paraproteinemias; Paraproteins; Peptide Fragments; Prognosis; Pyrazines; Randomized Controlled Trials as Topic; Renal Dialysis; Thalidomide

Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (SCT) or oral melphalan with dexamethasone (MDex). The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

Topics: Amyloidosis; Animals; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Melphalan; Paraproteinemias

Multiple mycloma causes a disproportionate amount of the malignancy-related renal insufficiency. Acute renal insufficiency in myeloma patients can occur due to dehydration, hypercalcemia, side effects of medications (NSAIDs) or tumor lysis syndrome in addition to cast nephropathy, amyloidosis and light chain deposition disease. Patients on hemodialysis have traditionally been excluded from antineoplastic therapy due to fear of side effects and lack of studies addressing benefit. Melphalan is the most effective chemotherapeutic agent in myeloma and its PK (pharmacokinetics) are not adversely affected by impaired renal function. Because of more pronounced toxicity of Melphalan 200 mg/m2 conditioning regimen, Melphalan 140 mg/m2 has become the standard of care. 24% of patients become dialysis-independent at a median of 4 months after autotransplantation. Favorable factors for becoming dialysis independent were duration of dialysis 10 ml/min. While no good data are available on the use of thalidomide in the presence of renal failure, it is our experience that severe neuropathy, constipation, lethargy and bradycardia are more frequent in patients with creatinine >or=3 mg/dl. It has become apparent that bisphosphanates-zoledronic acid more than pamidronate-cause renal dysfunction. If patients remain dialysis-dependent after autotransplantation, we recommend to delay considering a renal transplant until at least 3 years after the first transplant.

Topics: Antineoplastic Agents, Alkylating; Busulfan; Dose-Response Relationship, Drug; Humans; Kidney; Kidney Transplantation; Melphalan; Multiple Myeloma; Paraproteinemias; Renal Dialysis

Amyloidosis is a rare disease in which a specific protein is deposited as aggregated interstitial fibrils that can compromise organ function and lead to death. Immunoglobulin (Ig) light-chain amyloidosis (AL), caused by the monoclonal gammopathy of a plasma cell dyscrasia, is the most common type. A hereditary type is also caused by mutant transthyretin and other proteins. Rarely, a patient with amyloid has both a monoclonal gammopathy and a hereditary protein. In AL, circulating monoclonal Ig light chains can be measured with the free light-chain (FLC) assay and provide a target for therapy to eliminate the underlying plasma cell dyscrasia while supporting the patient's organ function. Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor FLC is eliminated. For patients with limited organ involvement, intravenous melphalan in doses from 100 to 200 mg/m2 with autologous stem cell support (SCT) is an effective approach and, when followed at 3 months post-SCT with adjuvant thalidomide and dexamethasone for persistent plasma cell disease, has a 1-year hematologic response rate of 77%. Monthly oral melphalan and dexamethasone for 1 year can also be effective therapy for patients too sick for SCT (67% response rate). Hematologic complete responses are usually durable and result in long-term survival and a variable degree of organ recovery. For patients with advanced cardiac involvement, the prognosis remains guarded even with treatment. Drugs effective in multiple myeloma are usually active in AL, depending on side effects. New agents such as bortezomib and lenalidomide have shown promising activity, and novel antibody-based approaches for imaging amyloid and accelerating removal of deposits are being actively investigated.

Topics: Amyloidosis; Combined Modality Therapy; Glucocorticoids; Humans; Immunoglobulin Light Chains; Immunosuppressive Agents; Melphalan; Myeloablative Agonists; Organ Transplantation; Paraproteinemias; Stem Cell Transplantation

Focal and segmental glomerulosclerosis (FSGS) is a common histological finding in patients with proteinuria. The natural history of the condition varies, and although it may be responsive to therapy, FSGS is an important cause of end-stage renal disease. FSGS can be caused by a variety of conditions, but it has been reported rarely in association with a plasma cell disorder.. Mayo Clinic databases were queried and cross-referenced for FSGS and plasma cell disorders. The diagnoses were confirmed, and relevant clinical and laboratory data were abstracted.. A cohort of 13 patients with "idiopathic" FSGS and a monoclonal plasma cell disorder were identified. Four patients had myeloma, and 9 patients had monoclonal gammopathy of undetermined significance. Patients treated for myeloma experienced improvement in their renal lesion, and the latter relapsed when the myeloma relapsed.. We show that FSGS and plasma cell disorders are temporally and epidemiologically linked. Therapy for the underlying plasma cell disorder can lead to resolution of FSGS. The emerging molecular pathogenesis of both FSGS and myeloma also provides potential mechanisms that link the 2 conditions together. Thus, physicians must rule out a plasma cell proliferative disorder in patients with FSGS before concluding that the renal lesion is idiopathic. Moreover, FSGS may respond favorably after the underlying plasma cell disorder is controlled.

Topics: Aged; Amyloidosis; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cohort Studies; Combined Modality Therapy; Comorbidity; Cytokines; Databases, Factual; Dexamethasone; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunoglobulin Light Chains; Kidney; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Multiple Myeloma; Myeloma Proteins; Paraneoplastic Syndromes; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Prednisone; Prevalence; Proteinuria; Recurrence; Remission Induction; Retrospective Studies; Time Factors; Vasculitis

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Humans; Immunoglobulin Light Chains; Kidney Diseases; Melphalan; Multiple Myeloma; Paraproteinemias; Stem Cell Transplantation

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Child; Diagnosis, Differential; Heavy Chain Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone; Prognosis; Time Factors; Vidarabine; Waldenstrom Macroglobulinemia

Topics: Acute-Phase Reaction; Adult; Aged; Amyloid; Amyloidosis; B-Lymphocytes; Biopsy; Child; Contraindications; Female; Heart Transplantation; Humans; Immunoglobulins; Immunohistochemistry; Joints; Male; Melphalan; Middle Aged; Nervous System; Paraproteinemias; Prednisone; Prognosis; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Skin; Staining and Labeling; Viscera

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.

Topics: Adrenal Cortex Hormones; Adult; Aged; Bone and Bones; Bone Diseases; Child; Collagen; Collagen Diseases; Female; Fractures, Bone; Humans; Hydroxycholecalciferols; Male; Melphalan; Microscopy, Electron; Middle Aged; Paraproteinemias; Tendons

The interrelation between plasma cell dyscrasia and myelofibrosis or agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct syndromes has been proposed: (1) plasma cell dyscrasia associated with simple marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting with AMM representing two distinct clonal diseases.. The authors report the case of a 68 year-old man seen initially with severe anemia, massive splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis coexisting with massive bone marrow infiltration with IgA lambda-producing plasmacytoid cells.. Cyclic therapy with vincristine, carmustine, cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the myeloma lasting for 2 years and complete resolution of all the clinical features resembling AMM.. The authors' observations and the report of two other patients in whom remission of AMM has been observed after myeloma treatment underline the broad spectrum of secondary abnormalities ranging from moderate bone marrow fibrosis to the full clinical expression of a syndrome closely mimicking AMM. These secondary abnormalities are potentially reversible even in the presence of advanced bone marrow fibrosis and massive splenomegaly.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Diagnosis, Differential; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Prednisone; Primary Myelofibrosis; Splenomegaly; Vincristine

Topics: Alkylating Agents; Amyloidosis; Anemia; Anemia, Refractory; Animals; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Blood Transfusion; Bone and Bones; Bone Marrow Examination; Bone Marrow Transplantation; Bone Neoplasms; Calcium; Combined Modality Therapy; Diagnosis, Differential; Heavy Chain Disease; Humans; Immunoglobulin D; Immunotherapy; Interferons; Kidney Failure, Chronic; Leukemia; Melphalan; Mice; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Myeloma Proteins; Osteolysis; Osteosclerosis; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisone; Radionuclide Imaging; Waldenstrom Macroglobulinemia

Topics: Adult; Aged; Arsenic; Benzene; Bone Marrow; Breast Neoplasms; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Ovarian Neoplasms; Paraproteinemias; Waldenstrom Macroglobulinemia

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Humans; Leukemia, Plasma Cell; Melphalan; Multiple Myeloma; Paraproteinemias; Plasminogen; Plasminogen Activators

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carmustine; Cell Cycle; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Drug Evaluation; Humans; Melphalan; Multiple Myeloma; Paraproteinemias; Plasma Cells; Prednisone; Prognosis; Random Allocation; Vincristine

There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV.. We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT.. Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events.. This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.

Topics: Bortezomib; Cyclophosphamide; Dexamethasone; Humans; IgA Vasculitis; Immunoglobulin A; Lenalidomide; Melphalan; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Peripheral Nervous System Diseases; Plasma Cells; Prednisone; Retrospective Studies; Rituximab

There is currently no standard treatment for monoclonal immunoglobulin (MIg)-associated C3 glomerulopathy, and treatment is often dictated by the extent of the monoclonal gammopathy. Although chemotherapy treatment for MIg-associated C3 glomerulopathy may stabilize renal function, the overall renal prognosis of MIg-associated C3 glomerulopathy is still poor with frequent progression to end-stage renal disease. We present a case of a 55-year-old man with IgG-κ gammopathy-associated C3 glomerulonephritis (C3GN) with bone marrow biopsy demonstrating 5 - 10 κ-restricted plasma cells. Following chemotherapy treatment unfortunately, the patient encountered relapsing courses of the disease. The patient subsequently received high-dose melphalan treatment followed by autologous hematopoietic stem cell transplant (ASCT). At 8 months follow-up, the patient remained hematologic response with stable kidney function. Since ASCT can offer durable hematologic remission, ASCT can potentially be a curative treatment option for patients with MIg-associated C3GN.
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Topics: Biopsy, Needle; Complement C3; Glomerulonephritis; Hematopoietic Stem Cell Transplantation; Humans; Kidney Glomerulus; Male; Melphalan; Middle Aged; Paraproteinemias; Prognosis; Transplantation, Autologous

POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.

Topics: Adult; Dexamethasone; Female; Humans; Hypogonadism; Melphalan; Paraproteinemias; POEMS Syndrome; Polyneuropathies; Thalidomide; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Female; Humans; Immunoglobulin G; Maintenance Chemotherapy; Male; Melphalan; Middle Aged; Paraproteinemias; Retrospective Studies; Scleromyxedema; Thalidomide; Treatment Outcome

A 70-year-old woman was admitted to our hospital because of fatigue and renal dysfunction and was diagnosed with light chain deposition disease (LCDD) with multiple organ involvement (kidney, thyroid gland, heart and eyes). After chemotherapy with bortezomib, cyclophosphamide and dexamethasone, hepatobiliary enzyme levels increased abruptly. A liver biopsy showed light chain deposition in Disse spaces. After two years of treatment with bortezomib, melphalan and prednisone (VMP) administered at shorter intervals relative to regular cycles, the patient showed a hematological and organ response. This case indicates that a relatively low dose intensity VMP regimen is preferable for elderly patients with LCDD with multiple organ involvement.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Female; Humans; Liver Function Tests; Melphalan; Paraproteinemias; Prednisone; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Causality; Cladribine; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Female; Humans; Lenalidomide; Leukemia, Large Granular Lymphocytic; Male; Melphalan; Methotrexate; Middle Aged; Multiple Myeloma; Neutropenia; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Prednisone; Protease Inhibitors; Pyrazines; Registries; Retrospective Studies; Thalidomide

Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS.. We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities.. Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died.. This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome.. This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Topics: Adult; Age of Onset; Female; Follow-Up Studies; Humans; Male; Melphalan; Myopathies, Nemaline; Paraproteinemias; Retrospective Studies; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

The following case shows corneal crystal formation in a patient in whom thee systemic work-up led to the diagnosis of a monoclonal gammopathy with increased monoclonal immunoglobulin G (IgG). We present the corneal signs and subsequent haematological investigations undertaken to establish this important association.. Systemic work-up of a patient with corneal deposits showed a monoclonal gammopathy with increased monoclonal immunoglobulin (IgG-type kappa). Corneal crystals, a rare, but significant, clinical finding, may be the initial presentation in a patient with monoclonal gammopathy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Combined Modality Therapy; Corneal Opacity; Crystallization; Cyclophosphamide; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin kappa-Chains; Kidney Failure, Chronic; Lenalidomide; Male; Melphalan; Middle Aged; Paraproteinemias; Paraproteins; Phacoemulsification; Postoperative Complications; Prednisone; Slit Lamp; Thalidomide

Topics: Adult; Disease Progression; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Topics: Brain Diseases; Coma; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Myeloablative Agonists; Paraproteinemias; Plasmapheresis; Prednisone; Scleromyxedema; Thalidomide; Treatment Outcome

Topics: Adult; Aged; Antibodies, Monoclonal; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Multiple Myeloma has been recognized since Ancient Times. The first well-documented case was reported in 1844 by Samuel Solly. The most commonly recognized case is that of Thomas Alexander McBean, a highly respectable tradesman from London in 1850. Mr. McBean excreted a large amount of protein that was described by Henry Bence Jones in the middle of the 19th century. Jones was a well-known physician and made many contributions to medicine. One of the best known cases of multiple myeloma was that of Dr. Loos that was reported by Otto Kahler. The recognition of plasma cells and subsequently their product, a monoclonal protein has been described in detail. The authors have reviewed the treatment of multiple myeloma including the novel agents, thalidomide, bortezomib and lenalidomide.

Topics: Adrenal Cortex Hormones; Alkylating Agents; Bence Jones Protein; Boronic Acids; Bortezomib; History, 19th Century; History, Ancient; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone; Proteinuria; Pyrazines; Stem Cell Transplantation; Thalidomide; Urethane

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

Aggressive treatment with high-dose i.v. melphalan followed by auto-SCT (HDM/SCT) is effective in inducing hematological and clinical remissions, and in extending survival in AL amyloidosis. Tandem cycles of HDM/SCT have been shown to increase hematologic complete response rates in patients with AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at the Boston University Medical Center were treated with a second cycle of HDM/SCT after failing to achieve a complete response after a first transplantation. A total of 11 of 57 patients (19%) treated with tandem transplantation developed high fever 12-24 h after melphalan administration. The average peak temperature was 39.1 degrees C. Other clinical features include hypotension, acute renal failure and skin rash. No infectious etiology was identified. One of the patients had serum available for measurement of cytokines before, during and after the febrile reaction. The concentration of several pro-inflammatory cytokines, including IL-6 and TNFalpha, increased significantly, showing a clear physiological response correlating with the clinical findings. We conclude that an unusual cytokine-mediated febrile reaction can occur in patients with AL amyloidosis exposed to a second cycle of high-dose melphalan, which we have termed a 'melphalan recall' reaction.

Topics: Adult; Amyloidosis; Antineoplastic Agents, Alkylating; Cytokines; Female; Fever; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Stem Cell Transplantation; Transplantation Conditioning

Topics: Antineoplastic Agents, Alkylating; Dose-Response Relationship, Drug; Humans; Male; Melphalan; Middle Aged; Myopathies, Nemaline; Paraproteinemias; Treatment Outcome

A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.

Topics: Adult; Drug Therapy, Combination; Glomerular Mesangium; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Glycosylation; Humans; Immunoglobulin A; Immunoglobulin kappa-Chains; Male; Mass Spectrometry; Melphalan; Paraproteinemias; Polysaccharides; Prednisolone; Protein Processing, Post-Translational; Treatment Outcome

An 8-year-old male Austrian Pinscher and a 14-year-old male Golden Retriever were presented for evaluation due to unexplainable high fructosamine values despite euglycemia and epistaxis in combination with polydipsia/polyuria, respectively. Blood analysis revealed severe hyperglobulinemia, hypoalbuminemia and markedly elevated fructosamine concentrations in both dogs. Multiple myeloma with IgA-monoclonal gammopathy was diagnosed by serum and urine electrophoresis including immunodetection with an anti-dog IgA antibody and bone marrow aspirations. Diabetes mellitus was excluded by repeated plasma and urine glucose measurements. Fructosamine values were positively correlated with globulin, but negatively correlated with albumin concentrations. These cases suggest that, as in human patients, monoclonal IgA gammopathy should be considered as a possible differential diagnosis for dogs with high fructosamine concentrations.

Topics: Animals; Blood Proteins; Dog Diseases; Dogs; Fructosamine; Immunoglobulin A; Male; Melphalan; Multiple Myeloma; Myeloablative Agonists; Paraproteinemias

Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy.. We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation.. Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.

Topics: Biopsy; Diagnosis, Differential; Electromyography; Female; Humans; Hypertrophy; Immunoglobulin kappa-Chains; Melphalan; Paraproteinemias; Peripheral Nervous System Diseases; Salivary Glands; Sialography; Sjogren's Syndrome; Stem Cell Transplantation; Tomography, X-Ray Computed; Transplantation, Autologous

Light-chain deposition disease (LCDD) is a multisystemic disorder associated with plasma cell dyscrasias and multiple myeloma. It is histologically characterized by the deposition of a homogeneous, in electron microscopy granular, slightly eosinophilic material showing positivity usually for kappa light chains. In contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly involves the kidneys as the predominant organ manifestation resulting in a nephrotic syndrome. However, involvement of other tissues such as liver and heart have been described. Here we report a case of severe ischemic cholangitis in a patient with multiple myeloma receiving chemotherapy with melphalan, prednisone, and lenalidomide. Histopathological analysis revealed LCDD of the hepatic arteries as the underlying cause. This is to our knowledge the first case of LCDD of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangitis; Hepatic Artery; Humans; Immunoglobulin Light Chains; Ischemia; Lenalidomide; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone; Thalidomide

Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-ras mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.. Cytokine determinations were performed by commercially available ELISA kits, while K12-ras mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.. Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-ras mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.. IGF-I reduction in the transition: Controls-->MGUS-->MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.

Topics: Aged; Antineoplastic Agents, Alkylating; Case-Control Studies; Female; Fibroblast Growth Factor 2; Genes, ras; Humans; Insulin-Like Growth Factor I; Male; Melphalan; Middle Aged; Multiple Myeloma; Mutation; Paraproteinemias; Vascular Endothelial Growth Factor A

Light-Chain Deposition Disease (LCDD) frequently recurs after renal transplantation, displaying a pernicious course. Herein we have described a 39-year-old Caucasian man with a history of immunoglobulin G-kappa multiple myeloma who failed two chemotherapy regimens, but ultimately responded to the combination of thalidomide, bortezomib, and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation 3 years prior to transplantation, during which time he showed no evidence of persistent or recurrent disease. At 3 days following spousal living related renal transplantation, he displayed a rapid deterioration of renal function requiring dialysis therapy. This episode failed to respond to empiric antirejection therapy including anti-thymocyte globulin, plasmapheresis, and anti-CD20 monoclonal antibody. Increasing evidence suggested recurrence of LCDD, including positive immunofluorescence staining of basement membranes and vessels for kappa light chains as well as free kappa light chains in his urine and serum. Following suspension of sirolimus, he was initiated on and responded to bortezomib (1.3 mg/m(2)) with discontinuation of dialysis within 3 weeks and progressively improving renal function. His maintenance therapy, in addition to six 2-week-long cycles of bortezomib separated by 1-week rest periods, includes cyclosporine (50 mg twice daily), prednisone (10 mg daily), and curcumin (9 g daily). In sum, bortezomib rescue therapy salvaged a spousal renal transplant afflicted with recurrent LCDD.

Topics: Adult; Antilymphocyte Serum; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Pyrazines; Recurrence; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Topics: Adult; Diagnosis, Differential; Humans; Male; Melphalan; Motor Neuron Disease; Myeloablative Agonists; Myopathies, Nemaline; Myositis; Paraproteinemias; Stem Cell Transplantation

Topics: Acute Kidney Injury; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome; Humans; Kidney Neoplasms; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Plasma Cells; Plasmacytoma; Prednisolone; Thalidomide; Urine

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

Topics: Antineoplastic Agents, Alkylating; Combined Modality Therapy; Female; Glucocorticoids; Granuloma; Humans; Melphalan; Middle Aged; Necrobiotic Disorders; Paraproteinemias; Prednisolone; Skin; Skin Transplantation; Ulcer; Xanthomatosis

A 63-year-old man, known to have Bechterev's disease was admitted because of weight gain and nocturnal sweating. He also had signs of heart failure with progressive exertional dyspnoea. Many months previously numerous bleedings had occurred in the skin, predominantly the face (periorbital and perioral), the inguinal region and the penis.. Extensive diagnostic test failed to find any evidence of tumor. The Rumpel-Leede tourniquet test was positive, while platelet functions was normal, suggesting vascular disease. The skin biopsy showed many perivascular amyloid deposits (AL). Immunochemical differentiation also demonstrated the same amyloid in rectal and hepatic biopsies. But there was AA amyloid in a hepatic artery. Immunophoresis indicated a biclonal gammopahty of unknown significance.. These findings indicated the diagnosis of primary AL amyloidosis associated with a gammopathy of unknown significance and a secondary AA amyloidosis in the presence of chronic Bechterev s disease. The clinical picture also showed cardiac complications, predominantly heart failure and numerous previous myocardial infarctions without S-T elevations. Echocardiography, which revealed marked thickening of the left ventricle with a restrictive filling pattern, suggested cardiac co-morbidity. The patient underwent chemotherapy with melphalan and prednisone but had a sudden cardiac death.. In a case of bleeding of unknown cause systemic amyloidosis should be considered in the differential diagnosis. A tendency towards bleeding, as in this patient, may be the first sign of amyloidosis, which ist often diagnosed quite late in the course of the disease.

Topics: Amyloidosis; Death, Sudden, Cardiac; Diagnosis, Differential; Fatal Outcome; Glucocorticoids; Heart Failure; Hemorrhagic Disorders; Humans; Male; Melphalan; Middle Aged; Myocardial Infarction; Paraproteinemias; Prednisone; Spondylitis, Ankylosing

A 56-year-old married female presented in May 1998 with a 5-month history of xanthelasma of the eyelids, followed 4 months later by two enlarged lymph nodes of the left side of the neck and three of the left axilla. At the same time, she developed xanthomatous patches on the face, neck, and shoulders (Fig. 1). The cutaneous lesions were xanthomatous nodules and plaques, affecting the periorbital regions. Later, the whole face was affected, followed by ulcerated lesions on the scalp, chest, back, and extremities (Fig. 2). The skin lesions became painful, pruritic, ulcerated tumors (Fig. 3). In July 1998, computed tomography (CT) scans of the chest and abdomen with contrast medium showed pretracheal, bilateral axillary, right retrochural, paracaval, aortocaval, and para-aortic lymph node enlargement. These findings were suggestive of lymphoma. CT scan also showed slight heterogeneous hypodensity in the upper part of the right lobe of the liver, suggesting fatty infiltration. The spleen, pancreas, and suprarenal glands appeared normal. One cervical and two left axillary lymph nodes were excised. They revealed total replacement of the nodular architecture by a diffuse proliferation of mature lymphoid cells having small nuclei and a crumbled chromatin pattern, and very rare mitosis. It was concluded from the lymph node biopsies that these changes were typical of non-Hodgkin's lymphoma, diffuse and small cell type, of low-grade malignancy. A bone marrow aspirate showed a marrow heavily infiltrated by lymphoid cells with some immaturity. The megakaryopoiesis was adequate. Trephine biopsies showed similar changes. Iron stores appeared to be absent. The bone marrow picture was consistent with diffuse, well-differentiated non-Hodgkin's lymphoma, developing into chronic lymphocytic leukemia (CLL). Endoscopy showed antral-type gastric mucosa exhibiting mild chronic gastritis. Skin biopsy from a fresh lesion on the back showed a diffuse inflammatory cell infiltrate with collections of histiocytic cells. It also showed necrobiotic foci, surrounded by mixed inflammatory cells, dark palisaded foamy histiocytes, and a few Touton giant cells. These findings are compatible with necrobiotic xanthogranuloma (NXG) (Figs 4 and 5). Blood film showed normochromic, normocytic erythrocytes with anisopoikilocytotic leukocytes and normal platelets. The sedimentation rate was 90 mm in the first hour. The blood picture also showed monoclonal IgG paraprotein (3170 mg/dL) of the kappa li

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cyclophosphamide; Female; Glucocorticoids; Granuloma; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Melphalan; Middle Aged; Necrobiotic Disorders; Paraproteinemias; Skin Diseases; Treatment Failure; Treatment Outcome; Xanthomatosis

AL amyloidosis, a systemic disorder characterized by widespread deposition of amyloid fibrils derived from monoclonal Ig light chains in organs and soft tissues, is typically caused by an underlying plasma cell dyscrasia. However, this disease can also be associated rarely with a B-cell lymphoproliferative disorder. In this report, we describe the presentation and clinical course of 16 patients with this association. Although amyloid-related organ involvement in these patients was typical of AL amyloidosis, the patients in this series were on average older and more likely to be female than patients with disease associated with a plasma cell dyscrasia. They were also more likely to have multisystem involvement. Treatment decisions were based primarily on the dominent hematopathologic features of the associated lymphoproliferative disorder. However, high-dose melphalan and stem cell transplantation was the primary therapy in 5 patients, and each of these patients had prolonged survival, ranging from 36 to 102 months.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Antineoplastic Agents, Alkylating; B-Lymphocytes; Bone Marrow Cells; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Radiotherapy; Treatment Outcome

Serum free light-chain (FLC) concentrations were measured by a sensitive nephelometric immunoassay in 66 patients with AL amyloidosis before and after treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). At 1 year after HDM/SCT, 27 patients (41%) achieved a complete hematologic response (CR), that is, disappearance of the monoclonal gammopathy previously evident by immunofixation electrophoresis (IFE) in serum and urine and of plasma cell clonality in the bone marrow. Abnormally elevated FLC levels became normal in 27 patients (41%), and decreased by >90% in 37 (56%). Average improvements in FLC were 94% for patients who achieved a CR and 72% for those who did not (P=0.0001). However, a reduction in FLC of >90% was associated with a similar high likelihood of clinical improvement and prolonged survival, whether or not patients achieved a CR. While CR, as defined by standard criteria, is a more stringent indicator of hematologic response than are decreases in abnormally elevated FLC levels per se, these measures of hematologic response are complementary, and decreases in FLC are more readily detected early after treatment than are the changes in IFE and marrow studies required to determine CR.

Topics: Adult; Aged; Amyloid; Amyloidosis; Bone Marrow; Culture Media, Serum-Free; Disease-Free Survival; Female; Humans; Immunoassay; Immunoelectrophoresis; Immunohistochemistry; Male; Melphalan; Middle Aged; Paraproteinemias; Remission Induction; Retrospective Studies; Stem Cell Transplantation; Time Factors; Transplantation, Autologous; Treatment Outcome

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

An 8-year-old female Shetland sheep dog had hyperproteinemia with a monoclonal gammopathy and a solid mass on the liver, which was histologically diagnosed as a plasma cell tumor. After the treatment of surgery and chemotherapy, serum protein level reduced to the normal range and the gammopathy was disappeared. These findings indicate the plasma cell tumor developed primarily from the liver.

Topics: Animals; Dog Diseases; Dogs; Liver; Liver Neoplasms; Melphalan; Paraproteinemias; Plasmacytoma; Prednisolone

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Bence Jones Protein; Humans; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisolone

Specific treatment of light-chain deposition disease has been reported as ineffective in altering the course of the severe or end-stage renal failure it causes. The authors describe a case of biopsy-proven primary light-chain deposition disease of the kidney, severe renal failure, and incipient dialysis dependency, treated by autologous peripheral blood stem cell transplantation, that led to reversal of dialysis dependency and sustained improvement in renal function.

Topics: Antineoplastic Agents, Alkylating; Humans; Immunoglobulin Light Chains; Kidney Failure, Chronic; Male; Melphalan; Middle Aged; Paraproteinemias; Peripheral Blood Stem Cell Transplantation; Remission Induction; Renal Dialysis; Transplantation, Autologous

Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; CD4 Antigens; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Clone Cells; Combined Modality Therapy; Culture Media, Conditioned; Cyclophosphamide; Disease Progression; Female; Humans; Leukemia, Lymphoid; Melphalan; Middle Aged; Multiple Myeloma; Neoplastic Stem Cells; Osteolysis; Paraproteinemias; Prednisone; Vincristine

Topics: Aged; Amyloidosis; Drug Therapy, Combination; Factor X Deficiency; Female; Humans; Melphalan; Paraproteinemias; Prednisone; Treatment Outcome

A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented. The lupus diagnosis was established together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.

Topics: Aged; Chloroquine; Female; Humans; Lupus Erythematosus, Systemic; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone

Topics: Aged; Biopsy; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Drug Therapy, Combination; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Melphalan; Paraproteinemias; Paraproteins; Plasmapheresis; Postoperative Complications; Prednisolone; Recurrence; Transplantation; Transplantation, Homologous

High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown.. In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow.. In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy.. Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.

Topics: Amyloid; Amyloidosis; Antineoplastic Agents, Alkylating; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Melphalan; Middle Aged; Paraproteinemias; Remission Induction; Transplantation, Autologous

We measured the serum levels of p53 mutant protein (p53M-ELISA) in 65 patients with plasma cell dyscrasia (PCD) and compared them with some conventional laboratory variables. Our aim was to assess, for the first time, the potential of this parameter as a new marker for laboratory management of PCD. Twenthy-tree out of 65 patients had monoclonal gammapathy of undetermined significance (MGUS) and 42 suffered from multiple myeloma (MM). MM patients, with no prior chemotherapy consecutively entered this study. They were treated with standard regimens of Melphalan and Prednisone (MP) and were analyzed for serum p53M level from the time of diagnosis to response to therapy or death. A subgroup of nine patients was regularly monitored for changes occurring in p53M levels during MP therapy. Serum levels of p53M were elevated in MM patients compared with MGUS and healthy controls (p = 0.002). Significantly higher p53M levels were shown by MM patients refractory to chemotherapy than by responding patients (0.38 ng/ml vs 0.22 ng/ml, p = 0.05). The measurement of serum p53M in the nine patients during the course of chemotherapy correlated with disease progression or response to therapy. If confirmed on a larger series of patients, these results suggest a potential role of serum p53 mutant levels in laboratory management of PCD patients.

Topics: Aged; Aged, 80 and over; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Prednisone; Prognosis; Tumor Suppressor Protein p53

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Fatal Outcome; Female; Humans; Immunoglobulin A; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Melphalan; Middle Aged; Paraproteinemias; Prednisone

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Corneal Diseases; Cyclophosphamide; Doxorubicin; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Thalidomide; Visual Acuity

Necrobiotic xanthogranuloma (NXG) is a rare non-X histiocytosis with conspicuous lesions on the periorbital skin.. A diabetic patient presented with NXG and a previous diagnosis of necrobiosis lipoidica on the legs over a period of almost 2 years before the development of the typical lesions of NXG on the periorbital regions, back, thighs and legs. The patient was found also to have developed lambda paraproteinemia.. Treatment with melphalan and prednisone resulted in great improvement of cutaneous lesions and paraproteinemia remission.. This case report details how melphalan and prednisone can be administered in the successful treatment of necrobiotic xanthogranuloma with lambda paraproteinemia.

Topics: Adult; Anti-Inflammatory Agents; Diagnosis, Differential; Drug Therapy, Combination; Female; Histiocytosis; Humans; Melphalan; Necrobiosis Lipoidica; Paraproteinemias; Prednisone

Several studies demonstrate that the BCL-2 and BCL-XL antiapoptotic genes are variably expressed in plasma cells of patients with multiple myeloma (MM). However, the plasma cell expression of BAX protein, their major proapoptotic partner, has not been investigated. Our initial Western blot analysis of myeloma cell extracts also suggested patient variability in the expression of BAX, which was not altered by exposure to interleukin 6. To further investigate the significance of BAX expression, we performed immunohistochemistry on archival bone marrow biopsies and compared BAX staining to BCL-2 immunostaining. Expression was first evaluated in 104 patients with reactive plasmacytosis, monoclonal gammopathy of undetermined significance/smoldering MM, or active MM. An increase (P < 0.05) in expression of both BAX and BCL-2 was detected in MM patients compared with patients with reactive plasmacytosis. Patients with monoclonal gammopathy of undetermined significance/smoldering MM had intermediate values. For correlations with outcome, expression was assessed in 43 patients at diagnosis who were treated with melphalan and prednisone; 30 at diagnosis who were treated with vincristine, Adriamycin, and dexamethasone; and 29 at relapse who were treated with second-line therapy. There was no correlation between BAX or BCL-2 expression and response to chemotherapy or duration of response or between BCL-2 expression and survival. However, patients who demonstrated extremely low plasma cell BAX expression had significantly increased survival. This was true for patients initially treated with melphalan and prednisone or vincristine, Adriamycin, and dexamethasone, as well as patients studied at relapse. BAX expression did not correlate with expression of proliferating cell nuclear antigen used as a marker of proliferation. These data indicate a myeloma-specific increase in BAX expression in plasma cells and suggest that low BAX expression identifies a cohort of patients with long survival, which is not specifically associated with low proliferating cell nuclear antigen expression.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; bcl-2-Associated X Protein; Biopsy; Blotting, Western; Bone Marrow; Cell Division; Dexamethasone; Disease-Free Survival; Doxorubicin; Humans; Immunohistochemistry; Melphalan; Multiple Myeloma; Paraproteinemias; Plasma Cells; Prednisone; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Recurrence; Time Factors; Vincristine

Topics: Aged; Antineoplastic Agents, Alkylating; Female; Granuloma; Humans; Immunoglobulin lambda-Chains; Melphalan; Necrobiotic Disorders; Paraproteinemias; Treatment Outcome; Xanthomatosis

Multiclonal gammopathies associated with multiple myeloma may result either from a neoplastic transformation of a cell clone undergoing immunoglobulin class switching or from independent transforming events yielding proliferation of unrelated plasma cell clones. The simultaneous presence of more than one neoplastic clone may possess regulatory implications in terms of cell proliferation, clonal expansion, secretion of M-components or response to chemotherapy. We report a patient, diagnosed with multiple myeloma stage IIIa, who presented with two well-defined homogeneous IgG1-kappa components in the serum (designated WER-1 and WER-2) with striking differences in their plasma concentration and response to the classic melphalan/prednisone treatment. Immunochemical characterization and amino terminal sequence analysis of both the heavy and light chains of each M-component undoubtedly determined their biclonal origin. WER-1 was identified as IgG1(VHII)-kappaI while WER-2 was classified as IgG1(VHIII)-kappaIII. The plateau phase was characterized by very low or undetectable levels of WER-2, a high, almost constant, concentration of WER-1 and the absence of Bence Jones proteinuria, whereas these parameters were completely reversed during the escape phase with levels resembling those observed at the time of diagnosis. The statistically significant negative correlation between the biclonal components and the different susceptibility to the treatment clearly suggests regulatory interactions between the clones WER-1 and WER-2.

Topics: Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bence Jones Protein; Fatal Outcome; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Interferon-alpha; Male; Melphalan; Multiple Myeloma; Paraproteinemias; Paraproteins; Prednisone; Sequence Analysis

A case of acute nonlymphocytic leukemia (ANLL) occurring 2 years after the diagnosis of multiple myeloma (MM) that had been treated by only one course of melphalan/prednisone chemotherapy is reported. Cytogenetic and fluorescence in situ hybridization analysis of peripheral blood cells revealed trisomy 8 as the sole cytogenetic defect at the time of diagnosis of ANLL. Two years earlier, when MM was diagnosed without any cytological evidence of co-existent myelodysplasia, chromosomal analysis of bone marrow cells showed the same pathological karyotype 47, XY, +8 in 14 of 20 mitoses studied. Our interpretation of this unusual cytogenetic finding is that at the time of diagnosis of MM, in spite of lacking cytological signs of myelodysplasia, an unrecognizable myelodysplastic syndrome must have been present which then evolved to ANLL.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, Pair 8; Disease Progression; Fatal Outcome; Follow-Up Studies; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Melphalan; Multiple Myeloma; Myelodysplastic Syndromes; Neoplasms, Second Primary; Paraproteinemias; Prednisone; Trisomy

Topics: Blood Glucose; Blood Proteins; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Fructosamine; Glucocorticoids; Glycated Hemoglobin; Hexosamines; Humans; Insulin; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Recurrence; Serum Albumin

Topics: Bone Marrow; Drug Administration Schedule; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Peripheral Nervous System Diseases

IgE levels in sera of patients with multiple myeloma (MM) were found to be similar to those of patients with monoclonal gammopathy of unknown significance (MGUS) and to normal controls. This is in contrast to the significant depression in the level of the other polyclonal isotypes in patients with MM. Immediate skin test response to common environmental allergens was also preserved in patients with MM as compared with normal nonatopic controls. One-year treatment of MM patients with alkylating agents caused a significant decrease in the monoclonal immunoglobulin level and induced a tendency toward decreasing IgE level but had no effect on the polyclonal immunoglobulin concentrations. These findings suggest that IgE production and immediate skin test response is not impaired by the pathologic process in MM patients, in contrast to the production of other polyclonal immunoglobulins. This demonstrates the dissociation between the response of the IgE antibody and the other isotypes.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Skin Tests

Topics: Aged; Female; Granuloma; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Melphalan; Necrobiotic Disorders; Paraproteinemias; Prednisone; Xanthomatosis

Topics: Acute Kidney Injury; Humans; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisolone; Renal Dialysis; Waldenstrom Macroglobulinemia

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.

Topics: Aged; Cyclophosphamide; Female; Humans; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Melphalan; Paraproteinemias; POEMS Syndrome; Thrombocytopenia

The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective.

Topics: Adult; Aged; Cobalt Radioisotopes; Drug Resistance; Erythrocyte Transfusion; Follow-Up Studies; Humans; Male; Melphalan; Methods; Middle Aged; Multiple Myeloma; Pancytopenia; Paraproteinemias; Radioisotope Teletherapy

We report the case of a patient with scleromyxedema with abnormal monoclonal gamma globulin of the kappa type who was treated with melphalan (Alkeran), an alkylating agent. After nine and one-half years of therapy, the patient showed myelomonocytic leukemia. The risk of secondary malignancies must be considered when weighting the benefits and risks of melphalan treatment.

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Leukemia, Myeloid; Male; Melphalan; Paraproteinemias; Scleroderma, Systemic

Neutrophil chemiluminescence (CL) as a measure of oxygen-dependent killing activity was evaluated in 3 groups of patients: (a) 63 patients with multiple myeloma (MM); (b) 31 subjects with monoclonal gammopathy of undetermined significance (MGUS); (c) 32 healthy controls. Neutrophil CL response was shown to be significant reduced both in patients with MM (p less than 0.001) and in subjects with MGUS (p less than 0.001). A significant difference was also observed between the results obtained in MM and those of MGUS (p less than 0.001). Treated MM patients showed a more severe impairment of neutrophil chemiluminescence response than that observed in untreated patients (p less than 0.001). It is suggested that the impairment of neutrophil CL response, possibly related to decreased killing activity, may play a role, along with other known causes, in the increased susceptibility to infection observed in MM patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Luminescent Measurements; Melphalan; Multiple Myeloma; Myeloma Proteins; Neutrophils; Oxygen Consumption; Paraproteinemias; Peroxidase; Prednisone; Tetradecanoylphorbol Acetate; Vincristine; Zymosan

Scleromyxedema is an uncommon fibromucinous connective tissue disease characterized by accumulation of mucinous material in the dermis. A monoclonal paraprotein is regularly identified. A review of the literature (57 cases) shows the exceptional association of scleromyxedema with multiple myeloma (8.7%) and macroglobulinemia Waldenström (3.5%). A man with scleromyxedema, IgG lambda paraproteinemia, and sclerodactylia--as a special sign of scleromyxedema--is reported. Melphalan is the drug of choice in serious cases, but not effective in sclerodactylia.

Topics: Fingers; Humans; Hypergammaglobulinemia; Immunoglobulin G; Male; Melphalan; Microscopy, Electron; Middle Aged; Multiple Myeloma; Paraproteinemias; Scleroderma, Localized; Skin; Skin Diseases; Syndrome; Waldenstrom Macroglobulinemia

The incidence of a lymphoreticular system malignancy in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome (RS), is 3.3 to 10.6%. In 89 cases in the literature, the second neoplasm was either reticulum cell sarcoma or large cell diffuse histiocytic lymphoma (DHL), and there were 61 cases of Hodgkin's disease (HD). In a few cases the lymphoma was simultaneously diagnosed, for other cases an association with preexisting CLL was reported. Appearance of lymphoma was associated with leukemia regression for only 4 patients with DHL and 3 with HD. We report one case of B-lymphocyte CLL with macroglobulinemia, treated with melphalan and prednisone, in which DHL developed and the hematologic and histologic signs of CLL and of paraproteinemia remissed. Such patients might constitute a subgroup or a variant of RS. Since the non-Hodgkin malignant lymphomas (NHML) are considered to be monoclonal neoplastic expansion of the B-cell or T-cell lymphocytes, and since in some cases it has been proved that the proliferative cell clone was the same as that of the initial lymphoproliferative disease, RS could be a dedifferentiation or a transformation of CLL, resulting in an aggressive clinical course. The inclusion in this syndrome of CLL cases associated with HD is still controversial. Many of these cases could be giant cell pleomorphic lymphomas, while, on the contrary, in typical cases this association might be merely fortuitous.

Topics: Blood Transfusion; Female; Hemosiderosis; Humans; Immunoglobulin M; Leukemia, Lymphoid; Lymph Nodes; Lymphatic Diseases; Melphalan; Middle Aged; Paraproteinemias; Prednisone; Syndrome

The technique of crossed immunoelectrophoresis (X-IEP) has been used to quantify free monoclonal light chains (LC) directly in the serum of patients with light chain disease, without preliminary gel or membrane filtration of serum to separate whole immunoglobulin. LC concentration is proportional to the area under an immunoprecipitin peak formed by LC in the patient's serum and an anti-LC antibody of appropriate specificity. Light chains of beta electrophoretic mobility can be processed in the standard X-IEP technique at pH 8.6. Light chains of gamma mobility must be processed in a modified technique using a pH of 5.0 and a carbamylated antiserum in the second dimension gel. Dose response curves obtained from the method in serial dilution experiments with sera from 18 patients gave correlation coefficients greater than or equal to 0.99. Replicate measurements of absolute LC concentration on the same specimens were within +/- 10%. The method can also detect polymerized light chains. Serum light chain levels were measured during the course of plasmapheresis therapy in three patients with light chain disease and renal failure. Light chain levels were shown to fall after plasmapheresis and to rise rather rapidly in the interval between treatments.

Topics: Acute Kidney Injury; Aged; Allopurinol; Calcitonin; Carmustine; Counterimmunoelectrophoresis; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Male; Melphalan; Paraproteinemias; Peritoneal Dialysis; Plasmapheresis; Prednisone; Vincristine

Chemotherapy with alkylating agents and Prednisone can achieve a prolonged median survival time in patients with multiple myeloma which lasts as long as the remission endures. Aggressive therapeutic regimens could not achieve a further tumor cell reduction as soon as a stable phase is reached. Waldenström's macroglobulinemia requires a therapeutic approach, which is adjusted to the individual case. Patients with small tumor mass and therapy responders have a significant prolonged median survival time compared to patients with large tumor mass and non-responders.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunoglobulin Fragments; Immunoglobulin Light Chains; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Plasmacytoma; Prednisolone; Vincristine; Waldenstrom Macroglobulinemia

Three cases of advanced macroglobulinemia (two with severe cryoglobulinemia) have been treated for 6, 4 and 3 years, respectively, with regular plasma exchange and, during the last two years, also with short courses of cytostatics. The plasma exchange regimen has given the patients a marked relief from hyperviscosity symptoms and may have contributed to the improved peripheral blood values and lowered P-IgM levels. Addition of cytostatics, however, was necessary to obtain a lasting remission.

Topics: Antineoplastic Agents; Cryoglobulinemia; Cyclophosphamide; Dose-Response Relationship, Drug; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Plasma Exchange; Prednisone; Waldenstrom Macroglobulinemia

Topics: Aged; Cryoglobulins; Female; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Melphalan; Paraproteinemias; Plasmapheresis; Prednisone

Topics: Amyloidosis; Drug Therapy, Combination; Female; Humans; Melphalan; Middle Aged; Oxymetholone; Paraproteinemias; Penicillamine; Prednisone

A 33-year-old man with overall renal function in the lower normal range had daily excretion in the urine of between 31 and 70 gm of protein composed entirely of free monoclonal K light chains. K light chains were also present in the serum. Serum protein electrophoresis and findings on bone marrow and lymph node biopsy were diagnostic of light chain disease. Amyloid was absent from renal tissue. General clinical improvement and almost total disappearance of protein from the urine followed treatment with phenylalanine mustard.

Topics: Adult; Allopurinol; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Male; Melphalan; Paraproteinemias; Proteinuria

Topics: Adult; Humans; Male; Melphalan; Paraproteinemias; Skin Diseases; Syndrome

Immunoblastic lymphadenopathy is a recently described lymphoproliferative disorder, presumably of B-cell origin. It is characterized by regional or generalized lymphadenopathy, usually associated with hypergammaglobulinemia or dysproteinemia. Other findings may be hepatosplenomegaly, dermatitis, fever, malaise, weight loss, and various altered immunologic reactions. Histologically, the involved lymph nodes show immunoblast, plasmacytoid, and plasma cell proliferation. This may be extranodal as well. The case reported here is one of the few followed up prospectively. The patient's purpuric eruption was an apparent manifestation of a type II mixed cryoglobulinemia. Differing from what has usually been reported, we noted hypogammaglobulinemia and findings in part of altered cell-mediated immunity. Despite leukopenia and anemia there were no infectious episodes. Although a satisfactory treatment regimen has not been established, there was beneficial response to prednisone and short courses of melphalan.

Topics: Allopurinol; Anemia; B-Lymphocytes; Cryoglobulins; Female; Humans; Leukopenia; Lymphatic Diseases; Melphalan; Middle Aged; Paraproteinemias; Prednisone; Purpura, Hyperglobulinemic

Serum beta-lipoprotein and other specific protein concentrations were measured in 56 patients suffering from multiple myelomatosis, "benign" paraproteinaemia or Waldenström's macroglobulinaemia and in 56 control subjects. The mean level of B-lipoprotein in untreated patients with multiple myelomatosis and macroglobulinaemia was significantly lower than that of the controls. Patients who responded to chemotherapy showed a rapid return to normal of the beta-lipoprotein concentration, while the level remained unchanged in most of those who did not.

Topics: Aged; Blood Protein Electrophoresis; Blood Proteins; Chlorambucil; Cholesterol; Female; Follow-Up Studies; Hemoglobinometry; Humans; Immunodiffusion; Lipoproteins, LDL; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Prednisolone; Ultracentrifugation; Waldenstrom Macroglobulinemia

Topics: Amyloidosis; Female; Humans; Melphalan; Middle Aged; Paraproteinemias; Peripheral Nervous System Diseases; Prednisone

An unusual, nodulocystic form of scleromyxedema (lichen myxedematosus) developed in a 48-year-old man with a six-year history of psoriasis. The scleromyxedema responded to intermittent therapy with melphalan and prednisone. Dermabrasion smoothed and softened the skin and increased the mobility of the perioral skin. Two months after remission of the skin lesions, psoriasis recurred.

Topics: Dermabrasion; Humans; Male; Melphalan; Middle Aged; Mucopolysaccharidoses; Myxedema; Paraproteinemias; Prednisone; Psoriasis; Recurrence; Skin Diseases

Topics: Adult; Agglutinins; Autoantibodies; Cold Temperature; Humans; Male; Melphalan; Paraproteinemias

In a patient with essential cryoglobulinemia with systemic, cutaneous, and neurologic manifestations and a mixed IgG-IgM cryoprotein, elimination of systemic and cutaneous disease manifestations, as well as notable reversal of neurologic impairment, followed therapy with melphalan. Levels of circulating cryoprotein decreased, but protein structure was unchanged by chemotherapy. Experience to date with alkylating agents suggests that this mode of treatment is the most effective currently available.

Topics: Cryoglobulins; Female; Humans; Immunoglobulin G; Immunoglobulin M; Melphalan; Middle Aged; Neurologic Manifestations; Paraproteinemias; Prednisone; Remission, Spontaneous; Skin Manifestations

The transformation of lymphocytes in cultures with phytohaemagglutinin (PHA) or with pokeweed mitogen (PWM) was carried out during treatment on 28 patients with paraproteinaemia and on 20 control subjects. 78.5% of the peripheral blood lymphocyte short-term cultures from the treated patients showed a subnormal PHA-induced but high PWM-induced lymphocyte transformation. The other 21.5% of the treated patients had a normal pattern of lymphocyte transformation. Eight of 12 untreated patients with multiple myelomatosis and four of five untreated patients with benign paraproteinaemia also had a subnormal lymphocyte transformation to PHA but a high response to PWM. Serial lymphocyte transformation studies in eight of 18 myeloma patients during chemotherapy revealed that the initial subnormal lymphocyte transformation to PHA subsequently became higher than that to PWM. 82% of the bone marrow cultures from the patients showed a higher PWM-induced than PHA-induced lymphocyte response, also suggesting a B cell type of disease. In both dose response and time dependent investigations peak transformation of peripheral blood lymphocytes did not always coincide.

Topics: Chlorambucil; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymphocyte Activation; Melphalan; Paraproteinemias; Prednisolone; Time Factors

Topics: Cyclophosphamide; Drug Therapy; gamma-Globulins; Heavy Chain Disease; Humans; Melphalan; Multiple Myeloma; Paraproteinemias; Waldenstrom Macroglobulinemia