Die Behandlung der Myelocytenleukämien mit Dibrommannitol

Zusammenfassung

Das Cytostaticum Dibrommannit zeigt ein dem Busulfan ähnliches, in vivo jedoch stark verzögertes alkylierendes Verhalten mit hoher Wirkungsselektivität auf die Granulopoese. Wie die klinischen Ergebnisse bei 32 Patienten, davon 29 chronischen Myelocytenleukämien mit insgesamt 128 Behandlungskuren, zeigen, sind bei oralen Dosen von 5–7 g je Kur Remissionen bei 85% der Myelocytenleukämien zu erreichen. DBM senkt die Leukocytenzahl intensiv, während Thrombocyten und Erythrocyten nur wenig beeinträchtigt werden. DBM wirkt rascher und auf die Milzschwellung intensiver als Busulfan und ist auch bei busulfanresistenten Fällen noch wirksam.

Summary

Dibrommannit (DBM=1,6-dibromo-1,6-dideoxy-d-mannitol) presents a cytostatic agent of the alkylating type. After oral application it is quickly and completely absorbed in the intenstine and is reabsorbed after the passage of the liver and gall bladder. Consequently its activation is markedly retarded and shows a cytostatic active blood level during 48 hours and more. DBM has a high selectivity of action on the granulopoiesis similar to busulphan. Clinical results in 32 patients are reported, twentynine of them having chronic myelocytic leukemia with 128 courses of treatment and a maximal period of therapy of 37 months. The average total dose was 23 g, the maximal dose 152 g. The dose per course was 5–7 g and the duration 24 days in average with a daily dose about 200–500 mg orally. Remissions could be achieved in 85%. In 38% they were complete remissions with normalization of the blood picture and complete regressions of the hepato- and splenomegaly. The mean duration of the remissions was 37 days, if a reneval increase of the white cell count above 10000 was taken as a yardstick. Ninetythree days passed in the average until the next maximum leukocyte count was observed. DBM intensively decreased the leukocytes. Thrombocytes and erythrocytes, however, were only slightly involved. The decrease of the white cells continued in some degree even further 3–4 months after the withdrawal of the compound. Leukopenie below 2000 was seen in 5%, thrombopenic purpuras in 4%. Initial effects of DBM occurred sooner than after busulphan treatment. Splenomegaly reacted more readily. DBM was even active in cases resistant to busulphan. After long term treatment with DBM, 4 patients developped a resistance. In myeloblast crisis DBM was ineffective.