E. Kelemen, S. Tura
Dec 1, 1985
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Journal
Annals of the New York Academy of Sciences
Abstract
During a 14-year period, 70 Hungarian and 55 Italian polycythemia Vera (PV) patients received mitobronitol (Myelobromol, dibromomannitol: DBM) pulse therapy (a total of 1500-3500 mg DBM, during 3 to 5 days), on two to four occasions a year. Patients did not receive any other cytostatic agents. There were no clinical problems of pulsetherapy-induced cytopenia, which have been seen on rare occasions with the usual prolonged DBM therapy. DBM pulse therapy is not ideal because: (a) remissions endure for a few months only; (b) they are not sufficiently prolonged, i.e., low normal peripheral blood counts (in two-thirds or all of the main hemopoietic systems) are not achieved in at least half of the patients; and (c) supplementary initial phlebotomies must sometimes be performed. However: (1) both primary and secondary drug resistance occur rarely, (2) hemopoietic regeneration was always undisturbed, even after 17 to 39 pulses (given to 10 selected patients) during 6 to 13 years of DBM pulse therapy; and (3) it appears to be considerably safe, as regards drug-induced leukemia. In fact, although the literature holds that DBM is an alkylating agent, only two cases of acute nonlymphocytic leukemia developed among more than 100 DBM patients observed for 5 years or longer, which appears to be in accord with the rate of spontaneous leukemia developing in PV; i.e., extra leukemia cases did not appear to develop. In any event, compared with the well-known chlorambucil trial of the PV Study Group, this low leukemia rate for an alkylating agent is remarkable. The following questions arose in the course of this study: Are the above-mentioned advantages of DBM pulse therapy attributable to pulse therapy versus prolonged one? Is chlorambucil-induced acute leukemia the consequence of its prolonged administration rather than of its alkylating power? These important questions need to be investigated further on a larger number of patients.