mitobronitol and Leukopenia

In a prospective, randomized trial the effectiveness of dibromomannitol (DBM), a brominated sugar alcohol derivative, was compared to busulfan in previously untreated patients. One hundred thirty-one patients were evaluated for response and survival. The effective dose of DBM was 4 mg/kg. The persistence of sensitivity to either DBM or busulfan was shown in a quantified fashion. Despite initial reports of the alleged unique effectiveness of DBM in treating chronic myeloid leukemia (CML), this study did not disclose any advantage of DBM over busulfan. Multivariate analysis investigating the importance of prognostic factors in CML indicated that age, sex, splenomegaly, and initial platelet count were important for predicting survival. Determination of such factors in CML are valuable in deciding those patients who could benefit from alternative forms of therapy. It also insures that study results are related to treatment rather than selection of patients with favorable or unfavorable prognostic factors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Busulfan; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Leukemia, Myeloid; Leukocyte Count; Leukopenia; Male; Mannitol; Middle Aged; Mitobronitol; Prognosis; Prospective Studies; Random Allocation; Thrombocytopenia

1,2-Anhydro-6-bromo-6-deoxygalactitol (BrEpG) and its D-mannitol analogue (BrEpM) intermediary metabolites in the conversion of dibromodulcitol (DBD) and dibromomannitol (DBM) into dianhydrogalactitol (DAG) and dianhydromannitol (DAM) have been prepared. The three types of derivative of each hexitol have been compared in their toxicities towards mice, tumour inhibitory activities against the Walker carcinosarcoma and haematological effects in rats. The bromoepoxides showed intermediate potency in all tests. The galactitol derivatives were always more potent than their mannitol counterparts. The mannitol derivatives were selectively myelosuppressive, being twice as toxic towards granulocytes as towards lymphocytes. The lymphotoxic activity of DBM, in particular, relative to its other toxic effects was particularly mild. These differences have been ascribed principally to the more rapid reactivity of DAG compared with DAM towards target nucleophiles, modulated by the influence of the bromine substituent on the transport properties of the dibromo- and bromoepoxy-derivatives.

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Dianhydrogalactitol; Lethal Dose 50; Leukopenia; Mannitol; Mice; Mitobronitol; Mitolactol; Rats