LINAC-based intensity modulated total marrow irradiation (TMI) in addition to myeloablative fludarabine/IV busulfan conditioning prior to allogeneic stem cell transplant for high-risk hematologic malignancies: A phase I study.

7045 Background: Total body irradiation (TBI) currently has limited use in stem cell transplant due to significant extra-hematologic toxicity. Intensity modulated total marrow irradiation (TMI) represents an innovative technique to selectively irradiate the bone marrow. We combined a fully myeloablative chemotherapy regimen with escalating doses of TMI in a Phase I trial in allogeneic stem cell transplant. (Id: Clinicaltrials.gov NCT00988013). Methods: A Phase 1 trial (3+3 design) for adult patients with high risk (HR) hematologic malignancies enrolled 14 patients who were transplanted from related (n=9) or unrelated (n=5) donors and included: HR acute lymphoblastic (ALL) (n=2) or myeloid (AML) (n=9) leukemia, HR multiple myeloma (n=2) and chronic myeloid leukemia (CML) (n=1) resistant to TKI. Median age was 52 years (range 20-65). Patients received fludarabine 160mg/m2, targeted i.v. busulfan (AUC 4800 μM/min) and IM-TMI (from 3 to 12 Gy). Dose Limiting Toxicity was defined as any grade 3 or 4 toxicity u...