Sequential high-dose ara-C and asparaginase versus high-dose ara-C alone in the treatment of XXXX with relapsed and refractory acute @entity1778 .

@entity1 @entity137 @entity19 @entity2664 @entity2033 @entity3052 @entity2734 @entity1778 @entity11402
In consideration of the full spectrum of hematologic and nonhematologic @entity137 juxtaposed to the response rates (Tables 2-5), it appears that for relapsed @entity1 with @entity3052 , six to eight consecutive doses of HDara-C or four doses started on days 1 and 8 have the optimal therapeutic index. These regimens are associated with a 25% CR rate and have comparable tolerable and reversible @entity137 spectra. An increase in the total number of doses to 12 does not appear to increase the remission frequency in relapsed @entity1 but does decidedly increase the spectrum, frequency, and severity of toxic manifestations. Studies of important pharmacologic determinants such as membrane transport and cellular accumulation of @entity11402 suggest that a lower unit dose may be just as effective, an approach that could potentially lower the frequency and severity of @entity137 . However, these concepts must be tested in suitably designed clinical trials. In contrast to the response rate noted in @entity1 with relapsed @entity3052 , @entity1 with refractory @entity3052 have a substantially lower CR rate (approximately 10%) when treated with HDara-C alone. These lower CR rates are comparable to those reported for other recently introduced new drugs such as m-AMSA and @entity2664 . In this setting of primary @entity1778 , multi-institutional and cooperative group trials of @entity2033 -ara-C----ASNase show a consistently higher response rate in the range of 30% to 50%. Why ASNase should especially contribute to this particular group is unknown at present. Studies show that the gene for @entity2734 synthetase is repressed in @entity3052 cells. It is speculated that in the initial @entity1778 cell population (as encountered in refractory @entity3052 ), the gene for @entity2734 synthetase is repressed and hence, the @entity1778 is sensitive to ASNase. In contrast, in the relapsed @entity1 with recurrent @entity1778 , the gene for @entity2734 synthetase may be @entity1778 would be ASNase-insensitive. The therapeutic index of HDara-C----ASNase is schedule dependent. In leukemic @entity19 , pretreatment or concurrent administration of ASNase and HDara-C leads to antagonism of both the therapeutic and toxic effects of HDara-C. These effects are consistent with similar effects of other protein synthesis inhibitors on ara-C @entity137 .(ABSTRACT TRUNCATED AT 400 WORDS)
