The document discusses three clinical trials for treating acute childhood leukemia and multiple myeloma: 1) The "total therapy" trials at St. Jude significantly raised cure rates for childhood acute leukemia from less than 10% to over 95% by applying all active drugs upfront instead of reserving them for relapse. 2) The first myeloma tandem transplant trial enrolled 231 patients, and at 10 years 33% were still alive and 15% had never relapsed. 3) Total Therapy 2 built upon Total Therapy 1 for multiple myeloma by using more intensive induction therapy, consolidation chemotherapy after transplants, and adding dexamethasone pulsing and thalidomide during maintenance.

1. Slide shows the tremendous progress made since the early 1960's in the treatment of childhood acute leukemia at St. Jude with their 'total therapy' trials, raising cure rates from <10% to >95% in contemporary trials. The underlying philosophy was to apply all active drugs at any one time up-front rather than reserving agents for the time of relapse.

2. The first ever myeloma tandem transplant trial – Total Therapy 1 – enrolled 231 patients. Shown are the long-term outcome results. At 10 years, 33% are alive and 15% have never relapsed (left panel). Duration of complete remission is depicted on the right, revealing 15 patients who are in continuous complete remission of the 94 who entered such state originally. These patients can be considered cured as all are beyond 10 years.

3. This slide shows the treatment diagrams for Total Therapy 1 (TT1, top) and Total Therapy 2 (TT2, bottom). The difference in TT2 v TT1 included: a) more intensive induction therapy; b) the introduction of consolidation chemotherapy after tandem transplants with Melphalan; and, c) the addition of Dexamethasone pulsing during the first year of maintenance. All patients were randomized to receive or not to receive Thalidomide, which we discovered here to have profound anti-myeloma activity in endstage disease.