8544 Background: Previous attempts to deliver total body irradiation and high-dose melphalan (MEL) as part of AT regimens have been unsuccessful. TMI using helical tomotherapy may improve the efficacy of MEL, and may cause less toxicity. Patients and Methods: We designed a phase I study for pts with stages I-III MM in response or with stable disease (SD) . Pts received MEL 200 mg/m2 and AT, followed by a tandem ablative regimen consisting of TMI and AT. Starting at 1000 cGy, dose levels were to be increased by 200 cGy per cohort up to 200 cGy twice daily×5 days. Following tandem AT, maintenance therapy consisted of dexamethasone 40 mg/day×4 days and thalidomide 50–200 mg/day for 6 months (mos) for pts in complete response (CR), or for a minimum of 12 mos for pts not in CR. Results: The median age was 53.5 years (35- 66). Twenty three pts (13 female, 10 male) with stages I (1 ), II (6), and III (16) MM received MEL at a median time of 10 mos (7–18) from diagnosis; 22 pts received TMI (1000 cGy through 1800 cGy); 1 pt did not received TMI due to post-MEL toxicities. The median time between MEL and TMI was 63.5 days (range, 44–119). Granulocyte recovery to >1000/microliter following Mel was 14 days (13–15) versus 15 days after TMI (range; 13–19). Platelet recovery to >20,000/microliter was identical: 13 days (range:0–16 versus 0–17). Reversible grade 3 non-hematologic toxicities by TMI dose levels included febrile neutropenia (levels 1 and 2: 1 pt each); none (level 3); fatigue (level 4: 1 pt). Dose limiting toxicities at level 5 (1800 cGy) included grade 3 abdominal pain requiring parenteral feeding (n:1) and grade 3 hypotension requiring pressor support (n:1), defining the maximum tolerated dose (MTD) at 1600 cGy. The estimated median radiation dose to normal organs was 14–64% of the targeted bone marrow dose in the 6 pts each treated at doses 1600 and 1800 cGy. Best responses included CR (n:6), very good partial response (VGPR, n:7) PR or SD (n:7), and 2 pts are too early to assess. At a median follow-up of 12 months (range, 1–24+ mos) 2 pts progressed (at 8 and 20 mos) and 11 pts continue on maintenance. Conclusion: We defined the MTD of TMI as 1600 cGy, and preliminary outcome is encouraging. A phase II trial of tandem AT with 1600 cGy of TMI is ongoing. No significant financial relationships to disclose.