THE ANTILEUKEMIC ACTIVITY OF 5-AZA-2 DEOXYCYTIDINE (AZA-DC) IN PATIENTS WITH RELAPSED AND RESISTANT LEUKEMIA

被引:67
作者
RICHEL, DJ
COLLY, LP
KLUINNELEMANS, JC
WILLEMZE, R
机构
[1] Department of Haematology, University Medical Centre, Leiden
关键词
5-AZA-2'-DEOXYCYTIDINE; LEUKEMIA; DNA; DIFFERENTIATION; INHIBITION; INDUCTION; CYTOSINE; CELLS; MICE;
D O I
10.1038/bjc.1991.258
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the present study we demonstrate that Aza-dC in combination with Amsacrine has major antileukaemic properties in patients who have not already received extensive Ara-C therapy. Eight out of 11 patients in their first relapse of acute leukaemia achieved complete remission. Cross resistance between Ara-C and Aza-dC was revealed by the lack of antileukaemic activity in five patients with with Ara-C resistant leukaemia. Combination therapy with Aza-dC/Ams-acrine induced a considerable period of a granulo-cytopenia (28-35 days), while the toxic effect on erythro- and megakaryopoiesis was comparable to that reported for high dose Ara-C/Amsacrine chemotherapy. Remarkable is the long disappearance time for leukaemic blast cells in bone marrow, i.e. 3-5 weeks in some cases. Analysis of cell membrane markers showed a loss of the early differentiation antigens CD34 and CD33 from leukaemic bone marrow cells after 7 days of Aza-dC treatment, which is suggestive of leukaemic cell differentiation. In the small group of patients tested for DNA hypomethylation no association existed between the degree of hypomethylation and clinical response. Non-haematologic side effects were considerable in patients receiving the highest dosages of Aza-dC and consisted of severe, although usually reversible, gastrointestinal and neurological complications. In comparison with Ara-C, Aza-dC causes less nausea and vomiting and is therefore better tolerated.
引用
收藏
页码:144 / 148
页数:5
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