Toshitaka Kobayashi

Clinical significance of elevated soluble interleukin-6 receptor levels in the sera of patients with plasma cell dyscrasias

Summary .We investigated the clinical significance of the serum soluble interleukin‐6 receptor (sIL‐6R) in 42 patients with plasma cell dyscrasias (27 with multiple myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS), and two with plasma cell leukaemia (PCL)). Serum levels of sIL‐6R in normal individuals were 77 ± 21 ng/ml (mean ± SD, n= 18); those in patients with MGUS and with MM were elevated (102 ± 33 ng/ml, mean ± SD, P < 0–05 and 126 ± 60ng/ml, mean ± SD, P < 0–01, respectively). Significant correlations were not found between the serum levels of sIL‐6R and known prognostic factors (C‐reactive protein, haemoglobin levels, calcium, creatinine, β2‐microglobulin, amounts of M‐protein, or percentages of plasma cells in bone marrow). Elevated serum sIL‐6R did not affect the survival of the patients with MM. Serial measurements of sIL‐6R together with the clinical course of patients with plasma cell neoplasias revealed a good correlation between the sIL‐6R level and disease activity. We conclude that sIL‐6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.

Pyothorax-associated lymphoma : An unusual case with biphenotypic character of T and B cells

Pyothorax-associated lymphoma is known to develop in patients who received an artificial pneumothorax for pulmonary tuberculosis some 30 to 40 years previously. Such patients exhibit large, immunoblastic lymphoma cells and often have a B-cell phenotype. We present a patient with an artificial pneumothorax and such a late developing lymphoma but with the unique finding of aberrant T- and B-cell phenotypes. Southern blot hybridization using immunoglobulin gene JH and T-cell receptor beta chain receptors revealed germline configurations. Lymphomas developing in immunocompromised patients, such as those with acquired immunodeficiency syndrome, may show such unusual phenotypes. The unusual phenotypes found in this patient provide evidence that his pyothorax-associated lymphoma was related to an immunocompromised state.

Chronic Neutrophilic Leukemia Associated with Monoclonal Gammopathy of Undetermined Significance

A 30-year-old man with chronic neutrophilic leukemia (CNL) in association with monoclonal gammopathy is presented. Physical examination on admission revealed moderate hepatosplenomegaly. Initial blood count showed neutrophilic leukocytosis (42.2 x 10(9)/1 with 90% mature neutrophils). Leukocyte alkaline phosphatase (LAP) score was elevated. Bone marrow aspiration showed myeloid hyperplasia without dysplastic features. Karyotypic and molecular analyses of bone marrow cells showed the absence of Philadelphia (Ph1) chromosome and bcr gene rearrangement. Because there was no underlying infection or neoplasm, he was diagnosed as having CNL associated with IgG kappa-type monoclonal gammopathy (IgG, 1,269 mg/dl). In addition to its association with monoclonal gammopathy of undetermined significance (MGUS), the present case was also characterized by spontaneous remission of CNL during the 12-year follow-up, accompanied by a gradual increase in serum IgG levels up to 3,000 mg/dl. As far as we know, there have been 19 cases of CNL associated with monoclonal gammopathy in the literature. The median survival of these cases was 5 years. Although there have been only 6 cases of CNL associated with MGUS, survival of these cases was particularly favorable. Taken together with the observation that leukocytosis and hepatosplenomegaly in the present case subsided without specific treatment, we speculate that myeloid proliferation in the present case may have been a leukemoid reaction to underlying monoclonal gammopathy.

Hodgkin Disease with Subsequent Transformation to CD30 Positive Non-Hodgkin Lymphoma in Six Patients

Previous studies have indicated that some patients with Hodgkin disease have an aggressive clinical course. However, their characteristics have not been elucidated.

Lupus Anticoagulant-Like Activity Observed in a Dimeric λ Protein Produced by Myeloma Cells

We report here a lupus anticoagulant (LA)-like activity observed in a 45-year-old man with Bence-Jones protein (BJP) λ-type multiple myeloma. This patient showed no clinical symptoms of thrombosis or bleeding diathesis. Laboratory examina-tion on admission showed mild anemia, prolongation of activated partial thromboplastin time (APTT) (APTT, 56.2 seconds; control, 29.1 seconds), normal prothrombin time, normal thrombin time, and massive proteinuria (2.3 g/d). The mix test with normal plasma showed the presence of circulating anticoagulant. Based on the assumption that the λ-type BJP may have been responsible for the prolongation of APTT, we purified the BJP from the patient’s urine using column works. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the purified protein was a 48-kd homodimer of immunoglobulin λ-chains. Addition of the purified dimeric λ-type BJP to the normal plasma prolonged both APTT and dilute Russell’s viper venom time (DRVVT) in a dose-dependent manner, and the negatively charged phospholipid-dependent prothrombinase activity was significantly inhibited in the presence of this protein. Furthermore, both the prolongation of DRVVT and the inhibition of the prothrombinase activity were almost completely abrogated under the condition of high ionic strength. These findings collectively suggest that the dimeric λ-type BJP showed LA-like activity via the mechanism of ionic charge.

CD30‐positive lymphoma in human T‐cell leukaemia virus type 1 carrier without monoclonal integration of HTLV‐1

Summary. CD30, Ki‐1 antigen, an activated T‐cell antigen, is a member of the nerve growth factor receptor family. This antigen is expressed on the lymphoma cells of some adult T‐cell leukaemia/lymphoma (ATL/L) patients and some patients with Epstein‐Barr virus infection. CD30‐positive large cell cutaneous T‐cell lymphomas occasionally integrate a defective HTLV‐1 provirus. We describe here an HTLV‐1 carrier who developed Ki‐1 lymphoma with no evidence of monoclonal integration of the HTLV‐1 proviral sequence.