Daunorubicin, 1 mg/kg by rapid intravenous infusion daily for 7 consecutive days, was given 7 cases with previously untreated acute promyelocytic leukemia. In order to prevent the possible exacerbation of disseminated intravascular coagulation due to a sudden release of procoagulant from abnormal promyelocytes damaged by the potent antileukemic drug, heparin was administered intravenously at daily doses of 150 mg concurrently with chemotherapy.
Complete remission occurred in 4 cases. Maintenance therapy consisting of 6 to 9 intravenous injections of daunorubicin at 7-day intervals followed by oral 6-mercapto purine at daily doses of 100 mg was given to these patients. Remissions lasted 27, 30, 68 and 128 weeks. There has been no sign of relapse in the latter two cases. up to the time of this report. The most serious side effects of treatment were severe neutropenia and thrombocytopenia lasting for 2 to 3 weeks after initiation of the therapy, necessitating an intensive antibiotic therapy and platelet transfusion. Fibrinogen level rose after instituting administration of heparin in 2 of the 4 patients treated successfully, while it temporarily decreased in the remaining 2 cases and started to increase first when the mass of abnormal promyelocytes diminished. In none of the cases the bleeding tendency was intensified during heparin administration.
Three patients died of intracranial hemorrhage after treatment for 1,4 and 5 days, respectively. The possibility that heparin gave rise to the fatal hemorrhage in these patients cannot entirely be excluded. It is noteworthy, however, that remission was not produced in any of 11 cases treated at our clinic with various antileukemic agents other than daunorubicin before the introduction of the present protocol, and that 6 of 7 patients in this group without combined use of heparin died also of intracranial hemorrhage with a median survival of 8 days after the establishment of diagnosis.
