melphalan and Hypergammaglobulinemia

Renal involvement is common in multiple myeloma. Although several types of renal disease are observed, most of them are considered to be specifically related to monoclonal immunoglobulin light chains. Myeloma cast nephropathy is the most frequent and sometimes associated with acute renal failure. AL amyloidosis and monoclonal immunoglobulin deposit disease are often presented as a nephrotic syndrome. In this review, we describe the pathogenesis and diagnosis of these three renal diseases. We also focus on the treatment of renal disease in multiple myeloma, in the view points of the chemotherapy to reduce M-protein and the prevention to reduce the risks of promoting renal injury.

Topics: Amyloidosis; Biomarkers; Combined Modality Therapy; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Hypergammaglobulinemia; Immunoglobulin Light Chains; Kidney Diseases; Melphalan; Multiple Myeloma; Myeloma Proteins; Plasma Exchange; Prednisolone

Long-term survival and outcome were determined for 80 patients with immunoglobulin light chain (AL) amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) more than 10 years ago. Seventeen (21%) patients died within the first year of treatment, of treatment-related complications (14%) or progressive disease (8%). Of the 63 surviving evaluable patients at one year, 32 (51%) achieved a complete hematologic response (CR). For all 80 patients, the median survival was 57 months (4.75 yrs). The median survival exceeds 10 years for patients achieving a CR after HDM/SCT, compared with 50 months for those not achieving a CR (P < .001). In conclusion, HDM/SCT leads to durable remissions and prolonged survival, particularly for those patients who achieve a hematologic CR.

Topics: Adult; Aged; Amyloidosis; Combined Modality Therapy; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Hypergammaglobulinemia; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Melphalan; Middle Aged; Stem Cell Transplantation; Survivors; Time Factors; Treatment Outcome

8 patients with plasmocytomas were treated with Endoxan and compared with 5 patients without any considerable treatment. Diagnosis, therapy and prognosis of plasmocytoma are discussed. Particularly mentioned are 3 patients with secondary tumours during cytostatic treatment, a plasmocytoma without paraprotein, a tumorous plasmocytoma with double paraproteinemia and a gammopathia with further development into a plasmocytoma 10 years later.

Topics: Aged; Alkylating Agents; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Hypergammaglobulinemia; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Male; Melphalan; Middle Aged; Plasmacytoma; Prognosis

Nineteen patients with light-chain deposition disease (LCDD) were studied retrospectively. This report presents data on long-term patient and renal survival and the response to intermittent administration of melphalan and prednisone. Immunoelectrophoresis or immunofixation demonstrated a monoclonal protein in the serum of 78% and in the urine of 84% of the patients; 16% had no demonstrable monoclonal protein in serum or urine. The median age at presentation was 51 years (range, 37 to 77 years). Twelve (63%) of the patients had a monoclonal protein of undetermined significance without evidence of myeloma. The typical glomerular lesion was a diffuse mesangial nodular lesion that was positive for periodic acid-Schiff (PAS) stain with acute and chronic tubulointerstitial changes. Fifteen patients had kappa light-chain deposition and four had lambda light-chain deposition. Five-year actuarial patient survival and survival free of end-stage renal disease were 70% and 37%, respectively. Seventeen patients received melphalan and prednisone, and one patient received chlorambucil and prednisone. All of the patients had some impairment of renal function at presentation, and 58% had a serum creatinine concentration greater than 354 mumol/L (4.0 mg/dL). There was either stabilization or improvement in renal function after chemotherapy in five of eight patients who had a serum creatinine concentration less than 354 mumol/L (4.0 mg/dL) at the initiation of therapy. Of the 11 patients with a high serum creatinine concentration (greater than 354 mumol/dL [4.0 mg/dL]), 82% progressed to end-stage renal disease despite therapy. Follow-up urine protein studies demonstrated at least a 50% decrease in urine protein excretion in five of 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypergammaglobulinemia; Immunoglobulin Light Chains; Kidney Diseases; Male; Melphalan; Middle Aged; Prednisone; Retrospective Studies; Survival Analysis; Time Factors

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

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Drug Therapy, Combination; Humans; Hypergammaglobulinemia; Interferon Type I; Melphalan; Methylprednisolone; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Prednisone; Vincristine

A 58-year-old woman presented with a history of premature onset of menopause, longstanding hepatosplenomegaly, monoclonal gammopathy, lower limb polyneuropathy of recent onset, diabetes mellitus, excessive perspiration and leg edema. Polyneuropathy and excessive perspiration improved following a course of prednisone and melphalan. The clinical and pathophysiological features fit the rare entity known as POEMS syndrome.

Topics: Drug Therapy, Combination; Female; Hepatomegaly; Humans; Hypergammaglobulinemia; Immunoglobulin G; Melphalan; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Polyneuropathies; Prednisone; Syndrome

A 66-year-old man with necrobiotic xanthogranuloma associated with paraproteinaemia is described. He also had long-standing normolipaemic plane xanthomata. Treatment was with melphalan 0.15 mg/kg body weight/day. Initially, three 5-day courses were given at 4-weekly intervals but a fourth course was necessary after a further 4 months because of a deterioration in both his skin and associated systemic symptoms.

Topics: Aged; Granuloma; Humans; Hypergammaglobulinemia; Immunoglobulin G; Male; Melphalan; Necrobiosis Lipoidica; Xanthomatosis

Topics: Chlorambucil; Cyclophosphamide; Drug Therapy, Combination; Humans; Hypergammaglobulinemia; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Orthopedic Equipment; Paraproteins; Plasmacytoma; Prednisone; Prognosis; Vincristine; Waldenstrom Macroglobulinemia

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

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

Hyperviscosity syndrome associated with IgA monoclonal gammopathy was diagnosed in 3 dogs. Continuous plasmapheresis and alkylation therapy with melphalan and cyclophosphamide induced sustained remission in each dog. There was resolution of clinical signs associated with hyperviscosity syndrome and rapid establishment of normal serum protein concentrations.

Topics: Animals; Blood Viscosity; Cyclophosphamide; Dog Diseases; Dogs; Female; Hypergammaglobulinemia; Immunoglobulin A; Male; Melphalan; Plasmapheresis

Topics: Animals; Carmustine; Cell Transformation, Neoplastic; Clone Cells; Colony-Forming Units Assay; DNA; Doxorubicin; Drug Resistance; Humans; Hypergammaglobulinemia; Interferons; Melphalan; Mice; Mice, Inbred BALB C; Multiple Myeloma; Vinblastine; Waldenstrom Macroglobulinemia

Topics: Animals; Bence Jones Protein; Blood Viscosity; Cat Diseases; Cats; Dog Diseases; Dogs; Hemorrhagic Disorders; Hypercalcemia; Hypergammaglobulinemia; Kidney Diseases; Lymphoma, Non-Hodgkin; Melphalan; Multiple Myeloma; Waldenstrom Macroglobulinemia

Only four cases of immunoglobulin E (IgE) monoclonal "gammapathies" have been reported previously. Discussed here is a 57 year old man who presented with hypertension and the nephrotic syndrome. A monoclonal IgE-kappa component (0.6 mg/ml), which did not appear as an M spike on protein electrophoresis, was demonstrated by immunoelectrophoresis in the serum and urine. The patient's condition deteriorated rapidly due to renal failure, and he died five weeks after the diagnosis was made. Pathologic examination disclosed extensive glomerular lesions, but amyloid was not detected by light or electron microscopy. The possible relationship between the monoclonal gammapathy and kidney impairment is discussed.

Topics: Acute Kidney Injury; Fluorescent Antibody Technique; Humans; Hypergammaglobulinemia; Hypertension; Immunoglobulin E; Kidney; Male; Melphalan; Middle Aged; Prednisone

Extramedullary plasmocytomas of the skin are rare, especially if a participation of the bone marrow is lacking. A 76-year-old patient developed multiple skin tumours within 2 months. In addition he showed an increase of serum immunoglobulin A. Histopathologically the tumours resembled reticulum cell sarcoma with few plasma cells, partly immature.

Topics: Aged; Blood Sedimentation; Humans; Hypergammaglobulinemia; Immunoglobulin A; Male; Melphalan; Multiple Myeloma; Prednisolone; Skin Neoplasms

Topics: Age Factors; Antibody Formation; Arteritis; Bence Jones Protein; Blood Protein Disorders; Blood Protein Electrophoresis; Clone Cells; Cyclophosphamide; Female; gamma-Globulins; Humans; Hypergammaglobulinemia; Immunochemistry; Leukemia, Lymphoid; Lymphocytes; Macroglobulins; Male; Melphalan; Multiple Myeloma; Plasma Cells; Terminology as Topic; Waldenstrom Macroglobulinemia