A triclonal gammopathy in a relapsing multiple myeloma patient, detected by immunosubtraction method.

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the malignant proliferation of a plasma cell clone that produces a monoclonal immunoglobulin. Diagnosis and management of patients with monoclonal gammopathies depend on accurate identification and characterization of monoclonal proteins. We present a 67-year-old male patient with anaemia, weakness and weight loss for six months. His physical examination was normal with no fever, and no bone lesions were present in the imaging studies. Laboratory investigations revealed low haemoglobin and albumin concentrations with high total protein and beta 2-microglobulin concentrations. Capillary zone electrophoresis with immunosubtraction method revealed a triclonal pattern of M-protein (IgG κ + IgG λ + IgA κ) which was not prominent with immunofixation electrophoresis. After bone marrow biopsy, MM with triclonal gammopathy was diagnosed and autologous stem cell transplantation was performed. Six months later, again a triclonal M-protein was detected by immunosubtraction method, and a relapse was confirmed with a second bone marrow biopsy. The occurrence of monoclonal and biclonal gammopathies can often be seen upon diagnosis in plasma cell dyscrasias and lymphoproliferative disorders, but triclonal paraproteins are very rare and their clinical significance is unknown. In this particular patient, triclonality was detected by an alternative method called immunosubtraction by capillary electrophoresis. The patient was resistant to therapy suggesting that more than one monoclonal M protein may be a negative prognostic factor, and with new technologies and methods, the number of patients with different monoclonal patterns may increase.

Hydroxy-itraconazole pharmacokinetics is similar to that of itraconazole in immunocompromised patients receiving oral solution of itraconazole.

BACKGROUND: The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole (ITZ), is not fully known. METHODS: Oral solution of ITZ was administered in 46 immunocompromised patients as a single 200 mg dose for at least 12 days. The plasma concentrations of ITZ, active OH-ITZ, and keto-itraconazole (keto-ITZ), an inactive metabolite, 12 h after administration were determined by LC-UV or LC-MS/MS. RESULTS: The mean±SD of plasma concentrations of ITZ, OH-ITZ, and keto-ITZ were 833±468, 798±454, and 3.94±2.68 µg/l, respectively. A greater correlation coefficient was observed between plasma concentrations of ITZ and OH-ITZ (r=0.90, P<0.01) than between OH-ITZ and keto-ITZ (r=0.44, P<0.01). Plasma concentration of OH-ITZ was inversely correlated with concentration ratio of keto-ITZ to OH-ITZ (r=-0.52, P<0.01). Plasma concentrations of ITZ and OH-ITZ were correlated with serum concentration of albumin (r=0.36, P=0.01 and r=0.37, P=0.01) and estimated glomerular filtration rate (r=-0.27, P=0.08 and r=-0.35, P=0.02). CONCLUSIONS: The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-ITZ, serum concentration of albumin, and renal function in immunocompromised patients. The plasma concentration of OH-ITZ was strongly correlated with that of ITZ. Prevention of fungal infections can be improved by determining the plasma concentration of ITZ or OH-ITZ.

Hyperviscosity as a complication in a variety of disorders.

For a considerable time, hyperviscosity syndrome has been widely recognized as a serious manifestation of polycythemia and plasma cell dyscrasia. In this article a number of conditions will be considered in which the association with hyperviscosity has been more recently recognized and is less widely known. These conditions are hyperleukocytosis, retinoic acid therapy, and connective tissue disease such as rheumatoid arthritis. The essential problems in the first two are the hugely elevated white cell count (WCC) and the mechanical properties of the leukocytes, in other words, their relatively poor deformability and their adhesiveness for the endothelium. In the last, the essential problem is hugely elevated plasma viscosity due to immunocomplexes. They lead to increased flow resistance, especially in the microvessels, abnormal flow, and significant clinical symptoms. The details of the causes of the hyperviscosity, the symptoms that result, and the forms of treatment are discussed.

The clinical significance of pure Bence Jones proteinuria at low concentration.

The clinical significance of Bence Jones (BJ) proteinuria at low concentration (less than 0.2 g/24 hours) was investigated in 33 unselected patients who had no intact monoclonal immunoglobulin in their serum. The great majority (79%) of the patients were recognized as having malignant lymphoproliferative diseases, such as chronic lymphocytic leukemia (46%), hairy cell leukemia (6%), and non-Hodgkin's lymphoma (27%), whereas only two patients (6%) had multiple myeloma or systemic amyloidosis. Five patients (15%) had no evidence of definite malignant immunoproliferative disorders at the time of recognition of BJ proteinuria. Three of them, who were excreting steadily low amounts of BJ protein in their urine for 47, 61, and 73 months, respectively, without development of any B-lymphocytic malignancy, were classified as having a monoclonal gammopathy of undetermined significance. In the remaining two patients, BJ protein disappeared spontaneously 14 and 18 months, respectively, after its recognition. The study indicates that pure BJ proteinuria, even when occurring at low concentration, is most consistently associated with malignant proliferations of B-lymphocytic origin. However, the possibility should be considered that the clinical spectrum of the monoclonal gammopathy of the light chain type also includes benign and transient forms.

Plasma fibronectin in hemoblastosis.

Fibronectin (FN) is a glycoprotein whose plasma concentrations are reduced in many pathological conditions. In patients with hemoblastosis plasma FN was correlated with some clinical and biological parameters (stage of the disease, hepatosplenomegaly, infections and DIC), in order to assess its value as a tumor marker. The results suggest a poor relationship between FN levels and the course of the disease. However, the behaviour of the protein in relation with treatment was dynamic.