The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia.

ESSHAGH Amn,4 ARTHUR SAWITSKY,5 STANLEY LEE, STEPHAN D. MILLS, ’ E. OMER BURGERT, Jn., ’ CHARLES L. SPURR,7 RICHARD B. PATTERSON,7 FRANKLIN G. EBAUCH,5 G. \VATSON JAMES, III. AND JoHN H. MOON#{176} T 1-IE BROAD objective of the present study was to determine whether coml)inations of chemotherapeutic agents could improve the frequency and duration of complette remission in children with acute lymphocytic leukemia. The complete remission induction rate for the more effective remission inducing agents, prednisone and vincristine, approaches 60 per cent ( tal)le 8 ) . Patients who do not enter remission have a significantly shorter sunvival.’’2 Iii the present study an effort was made to increase the initial cornplete remission rate l)y using prednisoiie and 6-mercaptopurine ( 6-MP ) in coml)mation. While drug administration during complete remission will prolong the duration of remission,1 relapse always occurs. A patient who relapses on drug treatment is generally refractory to subsequent administration of the same drug. In the present study, three remission maintenance programs were employed in an attempt to delay the development of this drug refractoriness or resistance ( fig. 1 ) . For details of the rationale for these programs, see Discussion. Briefly, the first program consisted of combined concurrent 6-MP and methotrexate ( MTX ) in full doses. This has been shown to he at least as good as the best single agent for remission maintenance, 6-MP. The second remission maintenance program included 6-MP alternated at 28-day intervals with MTX. Drug resistance to antimetabolites )robably results from the selec-