Linac Based Total Marrow Irradiation and Myeloablative Chemotherapy In Allogeneic Stem Cell Transplantation for High Risk Patients.

Abstract 4526

Intensity modulated total marrow irradiation (IM-TMI) represents an innovative technique to irradiate the bone marrow in hematologic malignancies. IM-TMI has been performed previously using tomotherapy in combination with a reduced intensity preparative regimen. Here we report 2 cases where IM-TMI 300cGy was delivered using a linear accelerator in combination with fludarabine/IV busulfan.

To plan IM-TMI, 5 mm-slice CT scanning from top of the head to the mid femur was performed with immobilization using a customized whole body alpha cradle. All bones (excluding the arms and lower extremities) were contoured as the clinical target volume. A 3 mm margin was added to obtain the planning target volume (PTV). The organs at risk (OAR) including the brain, lenses, lungs, liver, kidney, small bowel and heart were identified and contoured. The IM-TMI technique consisted of three separate treatment plans: the head and neck; trunk; and pelvis.

Patients received fludarabine 40mg/m2 on days -8 to -5. IV busulfan was given on days -5 to -2 targeting an AUC of 4800microM/min based on a pretransplant test dose. IM-TMI was delivered on day -5. The patients received a total of 300 cGy IM-TMI dose in two fractions, 8 hours apart.

Two patients were treated: one is a 63 year old male with multiple myeloma who relapsed within 6 months after an autologous transplant with new cytogenetic abnormalities; and the second is a 52 years old female with AML who failed initial induction chemotherapy and at the time of transplant was in complete remission after receiving a second induction and one consolidation chemotherapy. Both patients received PBSC from HLA matched siblings.

IM-TMI technique achieved 95% coverage of the PTV. The mean doses to the lenses and lungs were 99 and 195 cGy, respectively. Overall doses delivered to OAR were reduced by 20–67% on average when compared to standard total body irradiation. Treatment time was 44 min and 32 min for the beam-on and set-up, respectively, using the Varian 21 EX linac and MV imaging.

Both patients suffered Bearman grade 1 mucositis. No other extramedullary toxicities were observed. Both engrafted in a timely manner achieving neutrophil >0.5 × 10⁹/L at day 13 and 14, and platelet >20 × 10⁹/L at day 8 and 9, respectively. Full donor chimerism was noted by day +30. After follow up of 246 and 218 days, respectively, both patients are alive and in remission. One developed a grade 2 acute GVHD and none of them has chronic GVHD.

This study demonstrates for the first time the use of IM-TMI using a linear accelerator. The possibility of adding higher doses of IM-TMI to a myeloablative regimen without toxicity will be tested in a dose escalating clinical trial.