Simultaneous occurrence of acute myelogenous leukemia and seminoma of the testis.

Simultaneous tumors are rarely encountered during the course of acute leukemias. We report on a case of seminoma of the testis that occurred during the evolution of acute myelogenous leukemia. To our knowledge, this simultaneous association has not previously been described, but a causal relationship was not apparent in the present case. The likelihood of a common carcinogenesis existed, but direct exposure to carcinogens could not be established. Although the results of a physical examination and echography were normal at the time of diagnosis, we cannot exclude the presence of microscopic cancer of the testis. Since the dissemination pattern of seminoma is usually slower than that observed in this case and the disease remains limited to the lymph nodes for long periods following dissemination, the rapid development of the present case might have been attributable to the immunosuppression and the scrotal sepsis that occurred during the induction therapy. Immunosuppression might have stimulated the progression of a primary microscopic seminoma and the development of metastasis, whereas the scrotal sepsis and inflammation might have favored the occurrence of metastasis through bypass of the lymphatic barrier.

Specific quantification of heparin-dependent antibodies for the diagnosis of heparin-associated thrombocytopenia using an enzyme-linked immunosorbent assay.

In order to specifically detect heparin-dependent antibodies in patients with suspected heparin-associated thrombocytopenia (HAT), an adapted ELISA test was developed. Serum-platelet bindable IgG (SPb-IgG) were measured in the absence and in the presence of heparin in the sera from a/ 25 normal controls, 25 patients treated by heparin without thrombocytopenia, 29 thrombocytopenic patients not receiving heparin and b/ 12 patients with confirmed HAT. In the absence of heparin, the 12 HAT sera showed normal or elevated SPb-IgG levels (range = 10.4-36 Arbitrary Units or AU) as compared to healthy controls (8-17.1 AU). After coincubation of HAT sera with heparin (0.25, 0.50, 0.75, and 1 IU/ml), SPb-IgG levels were consistently elevated (range = 22.8-150 AU), and this increase in IgG binding (equal in mean to 200%) was always inhibited with 5 IU/ml of heparin. In contrast, a mean maximum increase in SPblgG levels of only 20% was registered in all control groups whatever the tested heparin concentration. Thus, this ELISA allows the specific diagnosis of HAT by demonstrating a serum IgG binding on platelets only in the presence of therapeutic concentrations of heparin.

Thrombocytopenia in systemic lupus erythematosus: association with antiplatelet and anticardiolipin antibodies.

Serum platelet bindable immunoglobulin G (SPbIgG) and anticardiolipin antibodies (ACA) have been assayed in SLE patients with (group A, n = 8) and without thrombocytopenia (group B, n = 8). Moreover, we studied the binding of serum IgG on platelet proteins using a Western blotting procedure. Increased levels of SPbIgG were found in all thrombocytopenic patients and in five cases of group B. A binding of serum IgG on platelet proteins (80 and 53 kDa) was seen in seven of eight thrombocytopenic patients and in only one case of group B. ACA were present in the serum of four patients in each group and a significant inhibition of ACA IgG by entire washed platelets was achieved in only two severe thrombocytopenic cases. These data suggest that participation of ACA to the platelet destruction can be evoked for a few SLE patients, whereas recognition of platelet protein determinants by lupus autoantibodies is necessary to the thrombocytopenia.

Tolerance evaluation of L-asparaginase loaded in red blood cells.

OBJECTIVE: A pilot clinical study was conducted to evaluate the toxicity of a single dose of L-asparaginase loaded in red blood cells (RBCs). METHODS: Thirteen patients received a single dose of L-asparaginase in the range 30-200 i.u.kg-1. The enzyme was loaded in one autologous blood unit using a lysis-resealing process. A control population of 33 patients receiving L-asparaginase intravenously were tested in parallel. IgG, IgM and IgE class anti-L-asparaginase antibodies were detected using specific radioimmunoassays. RESULTS: L-Asparaginase pharmacodynamic parameters may be greatly improved by administration of the drug after internalisation in RBCs as compared to intravenous injection of free drug. The drug elimination was prolonged and similar to that of circulating carrier. After one injection of 30 i.u.kg-1, plasma L-asparagine was eliminated in 10 days and this was extended to 50 days for 150-200 i.u.kg-1. The drug was well tolerated and only transient variations were observed for some of the biological parameters measured. We did not reach the maximum tolerable dose (MTD) of L-asparaginase loaded in RBCs. No significant clinical toxicity was detected. In particular, no immune adverse effects were observed. CONCLUSION: This study opens new perspectives for the clinical utilisation of L-asparaginase. This mode of administration of the drug is able to improve pharmacodynamic parameters and enzymic efficacy and to increase the general tolerance of the treatment.