SALVAGE THERAPY FOR RELAPSED OR REFRACTORY CHILDHOOD ACUTE LYMPHOCYTIC-LEUKEMIA BY ALTERNATIVE ADMINISTRATION A LYMPHOID-DIRECTED AND MYELOID-DIRECTED CHEMOTHERAPEUTIC REGIMEN CONSISTING OF DUAL MODULATION OF ARA-C HYDROXYUREA, AND ETOPOSIDE

Risk-directed chemotherapeutic regimens in recent use have improved th e prognosis of children with acute lymphocytic leukemia (ALL). However , many patients relapse during or shortly after cessation of the initi al continuation chemotherapy. Since achievement of a second complete r emission (CR) is the initial step in successful retreatment effort, it is important to develop salvage protocols for children with relapsed or refractory ALL. In the present study, we developed a new salvage pr otocol (MLL-93) and applied the concept of dual chemical modulation of cytarabine, hydroxyurea, and etoposide with the alternative administr ation of high doses of myeloid-and lymphoid-directed agents. We also p lanned to perform allogeneic bone marrow transplantation (BMT) followi ng a CR if patients had HLA-identical donor(s). The six patients treat ed with the MLL-93 protocol achieved a second CR. One patient in CR di ed of interstitial pneumonia after an unrelated allogeneic BMT. The ot her five patients have been in CR for 12-41 months. We suggest that th e concepts of alternative administration of lymphoid-and myeloid-direc ted drugs and biochemical modulation are useful in the treatment of ch ildren with relapsed or refractory ALL. (C) 1997 Elsevier Science Ltd.