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Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

A patient with acute myelomonocytic leukemia is reported. He had presented erythroderma and atypical cellular infiltration of the skin 4 months prior to the detection of leukemia in the peripheral blood and bone marrow. Aleukemic leukemia cutis is a rare condition which is characterized by leukemic cells invading the skin prior to the observation of leukemic cells in the peripheral blood. The cases of aleukemic leukemia cutis reported in the literature show little or no conformity in their clinical appearance. Enzyme cytochemistry, immunocytological and electron-microscopic studies are of considerable help in differentiating the cutaneous infiltrates and in establishing early diagnosis. We report herein a patient with erythroderma which regressed spontaneously, whereas microscopic examination of a cutaneous biopsy showed atypical cells infiltrating the dermis. After a period of 3 months, during which the patient remained free of lesions, he showed recurrence of the erythroderma while developing acute myelomonocytic leukemia. We feel this unusual presentation of aleukemic leukemia cutis should be added to the evergrowing list of cutaneous manifestations of leukemia.

The mononuclear cells in the peripheral blood of 17 adults with acute phase toxoplasmosis were characterized with monoclonal antibodies. The absolute number of lymphocytes was increased by the presence of high numbers of T-cells with a surface phenotype of T-cytotoxic/suppressor cells (OKT3+, OKT8+). Shortly after the onset of the infection these cells expressed activation antigens (OKT10+, OKIa+). These changes were more pronounced in patients with lymphadenopathy, but were also present in those without symptoms of the disease. The activation antigens disappeared in the first weeks after onset of the disease but the reversed OKT4/OKT8 ratio persisted for 2 to 4 months. It generally normalized in parallel with clinical recovery of the patients. In one patient, however, a reversed OKT4/OKT8 ratio was present for more than 1 year after the disappearance of the symptoms.

Monoclonal antibodies recognizing specific antigenic determinants of peripheral T-lymphocytes (OKT3PAN), helper T-cells (OKT4IND) and suppressor T-cells (OKT8SUP) were used to study the immune regulation in autoimmune thyroiditis. An indirect immunofluorescence microscopy method was employed to quantify the number of different subtypes. In addition, B-lymphocytes were also studied using a fluorescent surface Ig detection technique. Patients with autoimmune thyroiditis--independent of their clinical status--show a decrease in the number of suppressor T-lymphocytes. This finding, in agreement with other functional tests, indicates that the autoimmune phenomenon is linked to a decreased T-suppressor activity.

The monoclonal B cells present in the blood of three patients with Waldenstrøm's macroglobulinaemia were analysed according to phenotype and function. As a marker for the monoclonal nature of the detected immunoglobulin (Ig) molecules, the kappa/lambda-ratio (two patients) or the presence of idiotypic (Id) determinants (one patient) were used. With double immunofluorescence it was shown that the neoplastic blood B cells were heterogeneous in respect to maturation stage. In addition to B cells carrying membrane bound IgM and IgD (mIgM+/IgD+), both mIgM+/IgD- and cytoplasmic IgM+ blastoid cells could be detected in the blood of the patients. This heterogeneity was also reflected in the responses of the monoclonal B cells upon stimulation with mitogens and T cell factors. B blastoid cells and IgM secretion could be induced after in vitro culture in the presence of Staphylococcus aureus, Pokeweed mitogen or a combination of both mitogens. It was shown that also T cell factors were effective in inducing monoclonal B cell differentiation.

Colloidal gold was used as a marker for the light microscopic detection of leukocyte cell surface antigens with monoclonal antibodies. Leukocytes were first incubated with monoclonal mouse antibodies, and then with colloidal gold-labeled goat-anti-mouse antibodies. The cells were fixed and stable preparations were made. Positive cells displayed numerous dark granules all over their surface membrane. In electron microscopy, these granules appeared as patches of gold particles. This immunogold staining method proved to be a reliable tool for the enumeration of T-lymphocytes and their subclasses. Accurate cell recognition, based on morphology and cytochemistry, permitted rapid cell counting. The procedure was also applied on small volumes of whole blood. This approach was used as a microtechnique for the enumeration of lymphocyte subpopulations in pediatric patients. In normal peripheral blood, the intracellular enzymatic activities of the immunogold-labeled lymphocytes were detected by the classical cytochemical reactions. The staining patterns for acid alpha-naphthyl acetate esterase, acid phosphatase and beta-glucuronidase were identical to those found in smears of unlabeled cells. The cytochemical profile of the OKT-defined normal lymphocyte subpopulations was established.

Forty-two previously untreated patients with multiple myeloma were entered in a prospective, randomised trial comparing recombinant interferon alfa-2C monotherapy with VMCP (vincristin, melphalan, cyclophosphamide and prednisolone). Both treatment arms were comparable for the stratification variables such as paraprotein type, stage of disease, and renal function. Rec. interferon effected 14% responses and 29% minor responses, while 57 and 32% of VMCP-treated patients achieved a pathologically documented remission (P less than 0.001). The time on initial treatment was significantly shorter in the IFN group (3.2 months) than in the VMCP group (7.6 months). In four patients in the IFN arm, primary treatment had to be changed according to progressive or severe stationary disease. Since all four patients responded to second line therapy (VMCP) no significant difference has been observed between the two groups in survival (median follow-up greater than 12 months). Despite this clear superiority of the conventional four-drug polychemotherapy, there was some suggestion that IFN might be particularly active in cases with low tumor-burden (stage I, II), and light-chain or IgA paraprotein type.

Hematologic values and lymphocyte subpopulations were determined in normal fetal blood during the second trimester of gestation. In these samples the platelet, erythrocyte, and leukocyte counts were significantly lower than in adults. Large red blood cells with a high hemoglobin content were present. Before the twentieth week of gestation, erythroblasts made up about half of the nucleated elements. Lymphocytes formed most of the leukocytes, and their absolute numbers were comparable to those in adults. Most of the fetal blood lymphocytes expressed T- or B-cell surface differentiation antigens. The percentage of T-cells was lower and that of B-cells was higher than in the adult. A high OKT4/OKT8 ratio was present. It was due to a low percentage of OKT8-positive cells. Lymphocytes with a natural killer cell phenotype were rare. Most lymphocytes were OKT10 positive, but almost none reacted with the antithymocyte antibody OKT6. These results give additional information about the development of blood cells in early human life. They can be used as reference values for the prenatal diagnosis of hereditary or acquired anomalies of the hematologic and immunologic systems.