A phase II study of menogaril (7R-O-methylnogarol) in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group.

Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in second relapse or refractory were treated with menogaril, 100 mg/m2/day as a 90-min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47), and there was one partial response. Seven of eight responders were in first relapse with a 26% response rate among first relapse patients (7/27). The median duration of survival was 3 months for all first relapse patients and 4.3 months for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100% of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3 arrhythmias and one heart block). All had previously received anthracyclines. Remission duration was 1.6-48+ months; two patients underwent bone marrow transplantation and continue in CR at 36+ and 48+ months. The nontransplanted patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity of menogaril in this study were comparable to that of other clinically useful anthracyclines in AML. Further investigation of this agent in AML is warranted.

Plasmapheresis. A therapeutic option in the management of heparin-associated thrombocytopenia with thrombosis.

Heparin-associated thrombocytopenia with thrombosis (HATT) is an uncommon syndrome that is estimated to occur in 1-5% of patients with heparin-induced thrombocytopenia. Early diagnosis requires careful clinical surveillance, and the management of these patients can be complex. Cessation of heparin therapy and substitution or addition of oral anticoagulants, antiplatelet agents, dextrans, and prostacyclin analogues have been advocated. The authors are aware of only two case reports in the literature that examine the use of plasmapheresis as a therapeutic alternative. The authors report a case of a 53-year-old white man who developed HATT after a single protamine-reversed exposure to heparin. Controlled platelet aggregation studies performed before and after apheresis sessions documented a dramatic response and rapid normalization of platelet number and function in the patient. The authors conclude that plasmapheresis could be a valuable adjunct in the successful management of patients with HATT. When done in conjunction with platelet aggregation studies, an objective measurement of therapeutic efficacy can be achieved.

Chronic lymphocytic leukemia (CLL) terminating in multiple myeloma: report of two cases.

Two cases of multiple myeloma (MM) developed late in the course of chronic lymphocytic leukemia (CLL). An 81-yr-old white female developed, after 6 yr of CLL, IgAk MM with sheets of plasma cells abutting sheets of lymphocytes in the bone marrow, multiple pathologic fractures, and 0.26 g/24 free k light chains in the urine. A 74-yr-old white male developed, after 16 yr of CLL, k light chain MM with 20% plasma cells in the bone marrow, multiple panthologic fractures, and 3.7 g/24 hr free k light chains in the urine. In both cases the CLL had responded well to intermittent low-dose chlorambucil therapy, but the MM failed to respond to cyclic melphalanprednisone therapy. A review of 105 cases of CLL seen at the Geisinger Medical Center failed to turn up any other cases of MM developing during the course of CLL. The suggestion that there is an increased prevalence of MM in CLL is an attractive one because both diseases are B cell neoplasms and because of the increased frequency of asymptomatic monoclonal gammopathies in CLL found by others.

The activated partial thromboplastin time as a monitor of heparin therapy: a warning.

The degree of correlation between the whole blood clotting time (WBCT) and the activated partial thromboplastin time (APTT) was evaluated in 42 patients receiving intermittent intravenous heparin therapy. Correlation between the two tests was found to be poor (correlation coefficient 0.52), primarily for reasons related to characteristics of the APTT system employed. The relationship in vitro between the APTT and the level of heparin was evaluated and found to vary widely over a range of heparin concentrations. This study emphasizes the marked variability between various APTT systems and the dangers involved with substituting the APTT for the WBCT to monitor heparin without appropriate initial evaluation.