Treatment Algorithm

Our current approach to treatment of adult ALL is beginning to incorporate these principles of risk adapted therapy. We advocate strongly the participation in clinical trials for adults with ALL. For younger patients, we have turned our focus to trying to achieve the same improvements in outcome noted by the pedi-atric cooperative groups for high-risk adolescents, where DFS is now routinely over 70%. To this end, an intergroup trial (CALGB and SWOG) will treat patients younger than 30 years with a regimen that is currently being used in the Children's Oncology Group (COG) for all adolescents and other high-risk children with ALL. The ECOG continues to explore the benefit of allo SCT in first remission for suitable younger patients, and their preliminary results also appear encouraging.

Current clinical trial efforts for adults with precursor B and T ALL have been directed toward the addition of novel targeted agents to reduce MRD and prolong DFS. Based on preliminary results from the GMALL and MD Anderson Cancer Center, the incorporation of rituximab into front-line therapy for CD20+ precursor B ALL appears promising. The ongoing CALGB study, as noted above, explores the substitution of dexamethasone for prednisone during induction and postremission therapy, and incorporates an alternative monoclonal antibody, Campath-1H, during postremission therapy for CD52+ precursor B and T ALL.

For suitable patients with a t(9;22), t(4;11), or other high-risk ALL, an allo SCT in first remission remains our treatment of choice. For the t(9;22) patients, the addition of imatinib to frontline therapy may improve outcome. We are participating in a US intergroup trial that explores the addition of imatinib pre- and poststem cell transplant. Based on the exciting preliminary results described above in the section on Ph+ ALL, the incorporation of imatinib into standard induction and postremission therapy for older patients with ALL is rational, appears to be well tolerated, and significantly increases CR rates, with further follow up needed to validate the improvement noted in DFS and OS.

Finally, the outcome for patients with mature B-cell ALL has steadily improved, using short course-intensive therapy with fractionated alkylating agents, highdose MTX and cytarabine, and intensive CNS prophylaxis. The addition of rituximab for these strongly CD20+ patients may further improve response rates and has been incorporated into frontline therapies for mature B-cell ALL in both North American and European cooperative group trials.

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