IgD myeloma with multiple cutaneous plasmacytomas.

Extramedullary cutaneous plasmacytoma is an uncommon observation in clinical practice. In most of the cases it is usually an extension of underlying medullary plasmacytoma. This case report describes a patient with IgD myeloma who went into plateau phase following standard intravenous chemotherapy. After more than a year in plateau phase, he developed multiple fleshy nodular lesions in the skin. Biopsy of one of the lesions revealed relapse of myeloma in the skin. His IgD paraprotein remained in plateau phase and the bone marrow showed only 1% plasma cells. The patient has been treated with systemic intravenous chemotherapy followed by local radiotherapy.

Effects of interleukin 3 and interleukin 6 on platelet recovery in mice treated with 5-fluorouracil.

We have studied the effects of murine recombinant interleukin 3 (IL-3) and human recombinant interleukin 6 (IL-6) on platelet recovery after administration of 5-fluorouracil (5-FU) to mice. 5-FU at 250 mg/kg body weight was administered as a single i.p. injection, and treatment with IL-3 alone, IL-6 alone, or a combination of IL-3 plus IL-6 was initiated immediately following the 5-FU or after a delay of 2 days. In addition, the effects of the combination of IL-3 plus IL-6 were evaluated following delays in initiation of their administration until 4 or 6 days after 5-FU treatment. In all schedules, the IL-3 and IL-6 treatments were discontinued 8 days following 5-FU. IL-3 and IL-6 were given s.c. three times daily; each injection of IL-3 was 80,000 U, each injection of IL-6 was 5000 U, and the combination comprised separate injections of IL-3 and IL-6 at the same respective doses. The combination of IL-3 and IL-6, initiated immediately or 2 days following 5-FU, diminished the platelet nadir and increased platelet counts on individual days during the recovery phase, thus apparently decreasing the time required for recovery to a normal platelet level. However, using self-modeling nonlinear regression, in order to analyze variability in the duration of thrombocytopenia, statistically significant shortening of the period of thrombocytopenia could not be consistently demonstrated. Neither IL-3 alone nor IL-6 alone had any effect on the above parameters. Recovery of hematocrit values and white blood cell levels was unaffected by administration of either IL-3 or IL-6 alone or the combination of both cytokines. We propose that IL-3 and IL-6 can act synergistically to enhance platelet recovery following 5-FU-mediated thrombocytopenia, but their modification of the response to 5-FU is modest.

Pseudo-Gaucher cells.

A case of acute lymphoblastic leukaemia, associated with cells resembling Gaucher cells in the bone marrow, is reported. The patient had no evidence of inherited Gaucher's disease and the ultrastructural appearance of the cells was consistent with pseudo-Gaucher cells described in other haematological diseases. This is the first report of these cells in association with acute lymphoblastic leukaemia.

Multiple in vivo effects of interleukin-3 and interleukin-6 on murine megakaryocytopoiesis.

The in vivo effects of interleukin-3 (IL-3), interleukin-6 (IL-6), and a combination of IL-3 plus IL-6 on murine megakaryocytopoiesis and thrombopoiesis were examined. Human recombinant IL-6 was administered subcutaneously as 14 equal injections of 5,000 units each during a 102-hour period. Murine recombinant IL-3 was given as 8 injections of 80,000 units each during the first 54 hours. Megakaryopoiesis and thrombopoiesis were evaluated 120 hours after initial administration of the cytokines. Platelet levels increased by 20% following IL-3 alone, 35% following IL-6 alone and 61% after administration of both IL-3 and IL-6. Platelet production, as measured by 75Se-selenomethionine incorporation, increased by approximately 120% in animals that had received IL-6 or IL-3 plus IL-6. Megakaryocyte ploidy analysis by two-color flow cytometry showed a shift in the modal ploidy class from 16N to 32N and a significant increase in the frequency of 64N cells only in IL-6 treated animals. Both bone marrow and splenic megakaryocyte colony-forming cells were significantly increased following either IL-3 or IL-6. Bone marrow megakaryocyte size increased 18%, 43%, and 38%, respectively, after administration of IL-3, IL-6, or the combination of IL-3 plus IL-6. Leukocyte counts and hematocrits were unaffected by either cytokine. Additional groups of mice received the same injection schedule as above and the serial effects on peripheral blood cell levels were assessed for 30 days. Platelet levels, which had been elevated by IL-3 or IL-6, fell to control values within 4 days following the last injection. Animals given IL-6 or IL-3 plus IL-6 were subsequently thrombocytopenic relative to controls on days 7 through 9 following cessation of treatment. Temporary 'cycling' of platelet levels was observed for 3 weeks following treatment with IL-6 or the combination of IL-3 plus IL-6. We conclude that IL-6 and to a lesser extent IL-3 stimulate platelet production in vivo and that their combined effects on platelet levels are approximately additive. Following discontinuation of IL-3 or IL-6, the effects are rapidly reversed, presumably by negative feedback mechanisms, resulting in a period of 'rebound thrombocytopenia' in mice that had received IL-6.

Autoimmune cytopenias in Castleman's disease.

The authors report a case of Castleman's disease in which the major clinical problems have been caused by severe thrombocytopenia and neutropenia. The cytopenias were caused by autoimmune destruction of mature cells as demonstrated by bone marrow findings and cell-specific antibody assays. There also was evidence of red cell autoantibody production but no overt hemolysis. The thrombocytopenia currently is controlled by intermittent vincristine, having proved refractory to steroids, splenectomy, and danazol and only partially responsive to high dose intravenous immunoglobulin. The neutropenia showed temporary improvement with immunoglobulin but has been resistant to all other therapy. This case provides further evidence for disordered immune regulation in Castleman's disease.

Results of the First International Granulocyte Serology Workshop.

Eleven laboratories participated in the First International Workshop of Granulocyte Serology. Participants were asked to identify any granulocyte-reactive antibodies present in 12 human sera distributed as unknown samples. Granulocyte immunofluorescence and granulocyte micro-agglutination were the most commonly used techniques. The incidence of false-positive and false-negative reactions was 15 and 4%, respectively. Most laboratories were able to distinguish between granulocyte-specific and anti-HLA antibodies using platelet absorption. The identification of the specificity of granulocyte-specific antibodies caused the most problems; these were correctly identified on only 57% of occasions.

Use of frozen neutrophils in serological testing.

We describe an immunofluorescence test to detect neutrophil-specific antibodies using neutrophils fixed to a slide and frozen prior to use. In titration studies using NA1, NA2 and NB1 antisera the technique was less sensitive than the standard immunofluorescence test but did enable slides to be stored for at least 5 months with no loss of NA1, NA2 and NB1 antigens. This technique can be used as a simple alternative to neutrophil cytoplasts for the identification of neutrophil antibodies. However, its use as a screening test in neutrophil serology is limited by the occurrence of false negative reactions with weakly reactive antisera.

Familial thrombocytopenia and myopathy.

We report a family in which a combination of myopathy and thrombocytopenia is transmitted as an autosomal dominant characteristic through three generations. The myopathy has unusual histological features with type II fibre atrophy and vacuolation while the thrombocytopenia appears to be due to a defect in megakaryocyte maturation, platelet morphology and function being normal. The haematological findings in such a family have not been described previously.

Familial myopathy associated with thrombocytopenia: a clinical and histomorphometric study.

We describe an unusual vacuolar myopathy with tubular aggregates in a mother and son from a family presenting with a slowly progressive, predominantly limb girdle, weakness and distal upper limb weakness in association with reduced blood clotting ability. To our knowledge this is the first report of a familial clinical defect of both muscle and platelets in the same individuals. The possibility that the primary defect may be due to an abnormality of the tubular intramembranous systems in muscle cells and platelet precursors is discussed.