losartan-potassium and Waldenstrom-Macroglobulinemia

Waldenström's macroglobulinaemia is a rare B-cell malignancy. It is prevalent in the sixth and seventh decades, the median age at diagnosis being 63 years. Conventional treatment has involved alkylator therapy, especially chlorambucil given daily at a low dose or intermittently at a higher dose. Purine analogues, used initially as salvage therapy in refractory disease, are increasingly used for initial therapy. However, purine analogue therapy entails significant complications, including immunosuppression, pancytopenia and autoimmune haemolysis. Moreover, it is unclear whether purine analogues extend survival. All of these need to be considered before initiation of therapy. More recently, anti-CD20 monoclonal antibody and thalidomide have been used with a 30% response in treated patients. High-dose therapy with stem cell support achieves a partial response in a majority of patients receiving this modality of therapy. The median survival of 5 years has not improved considerably since the introduction of purine analogues. Complete response is still uncommon; using all available modalities of therapy may increase the complete response rate and improve survival. Great strides in understanding the malignant cell, the microenvironment and the potential interactions have identified potential targets for therapy in multiple myeloma. These agents may also be useful in Waldenström's macroglobulinaemia. Since this is a rare malignancy, all patients should be treated with well-designed clinical protocols to achieve improvement in outcome.

Topics: Antibodies, Monoclonal; Antineoplastic Agents, Alkylating; Erythropoietin; Humans; Interferon-alpha; Plasmapheresis; Prognosis; Purine Nucleotides; Splenectomy; Thalidomide; Waldenstrom Macroglobulinemia

Topics: Aged; Erythropoietin; Female; Humans; Recombinant Proteins; Time Factors; Treatment Outcome; Waldenstrom Macroglobulinemia

Topics: Aged; Anemia, Refractory; Erythropoietin; Female; Humans; Leukemia; Lymphoproliferative Disorders; Male; Middle Aged; Recombinant Proteins; Waldenstrom Macroglobulinemia

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.

Topics: Adult; Aged; Animals; Blood Pressure; Blood Viscosity; Erythropoietin; Exchange Transfusion, Whole Blood; Female; Hematocrit; Humans; Kidney; Male; Middle Aged; Multiple Myeloma; Oxygen; Rats; Rats, Sprague-Dawley; Rats, Wistar; RNA, Messenger; Waldenstrom Macroglobulinemia

Immunoreactive levels of serum erythropoietin (EPO) have been measured in 95 patients with multiple myeloma (MM) and 12 patients with Waldenström's macroglobulinaemia (MW). Of the MM patients 23% were uraemic (mostly light and moderate renal failure) and 61.7% were anaemic. In the anaemic nonuraemic MM patients the mean serum EPO titre was 106.8 +/- 30.4 mU/ml which, when related to the extent of anaemia, was found to be appropriately elevated for the degree of anaemia (the mean haemoglobin (B-HGB) concentration was 6.66 +/- 1.31 mmol/l). The mean serum EPO concentration in uraemic and anaemic MM patients was 39.2 +/- 9.2 mU/ml, which was markedly lower than serum EPO levels in the non-uraemic MM patients, but still higher than in nonanaemic control subjects (22.5 +/- 8.5 mU/ml). The mean B-HGB concentration in uraemic MM patients was 6.04 mmol/l. In the anaemic MM patients with severe renal failure (S-creatinine levels greater than 400 mumol/l) the compensatory secretion of EPO was inadequate in relation to the degree of anaemia. The data indicate that unless the hypoproliferative anaemia of MM is accompanied by considerable renal failure the anaemia does not appear to be associated with a deficient biogenesis of EPO. Likewise the anaemia found in patients with MW also seems, generally, to elicit an appropriate increase in EPO secretion. Reasonably clinically stable MM patients with anaemia and uraemia may be candidates for replacement therapy with recombinant human erythropoietin (rhEPO).

Topics: Anemia; Erythropoietin; Female; Hemoglobins; Humans; Male; Multiple Myeloma; Uremia; Waldenstrom Macroglobulinemia

Topics: Agammaglobulinemia; Antibiotics, Antineoplastic; Antibodies, Heterophile; Blood Protein Disorders; Cell Differentiation; Cell Transformation, Neoplastic; Clone Cells; Erythropoietin; Fluorescent Antibody Technique; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Multiple Myeloma; Myeloma Proteins; Plasma Cells; Waldenstrom Macroglobulinemia

Topics: Binding Sites, Antibody; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Culture Techniques; Erythropoietin; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Macrophages; Methods; Microscopy, Electron; Mitosis; Multiple Myeloma; Neoplasms; Phagocytosis; Thymidine; Tritium; Waldenstrom Macroglobulinemia

Topics: Acetylcholinesterase; Alkaline Phosphatase; Anemia; Anemia, Hemolytic; Anticoagulants; Australia; Blood Transfusion; Chromium Isotopes; Coombs Test; Dextrans; Diagnosis, Differential; Drug Therapy; Epoetin Alfa; Erythrocyte Count; Erythrocytes; Erythropoietin; Hematologic Tests; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Hemosiderin; Humans; Iron; Iron Isotopes; Phenindione; Prednisone; Splenectomy; Waldenstrom Macroglobulinemia