1062 - Radiation-Related Late Toxicities Following Total Marrow Irradiation Transplant Conditioning Regimens

C. J. Ladbury¹, S. V. Dandapani¹, C. Han¹, S. K. Hui¹, D. Yang², G. Marcucci³, J. Rosenthal³, A. M. Monzr³, R. Nakamura³, A. Stein³, A. Liu¹, and J. Y. C. Wong¹; ¹Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, ²Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, ³Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA

Purpose/Objective(s): Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have been developed as a component of organ sparing myeloablative conditioning hematopoietic cell transplant (HCT) regimens via delivery using intensity-modulated radiation therapy, with the goal of achieving reduced toxicities and potentially dose-escalation. However, long-term toxicities after TMI/TMLI are not well characterized. This study sought to prospectively quantify pulmonary, renal, thyroid, and cataract toxicities as part of a trial that monitored after TMI/TMLI. Materials/

Methods: A total of 302 patients with primarily multiple myeloma or acute leukemia undergoing HCT with TMI/TMLI conditioning were prospectively followed after treatment as part of an IRB-approved prospective trial. Follow-up included pulmonary function tests, serum creatinine, glomerular filtration rate, thyroid panel, and ophthalmologic examinations performed at 100 days, 6 months, and annually thereafter, though not all patients had assessments for each toxicity. Median TMI dose was 12.5 Gy (10-20 Gy) delivered at 1.5 to 2.0 Gy twice per day at a dose-rate of 200 cGy/min. Radiation-related toxicities including pulmonary toxicity, renal toxicity, hypothyroidism, and cataract formation after HCT were evaluated using cumulative incidence, reported at 8 years. Patients with organ impairment preceding transplant were excluded.

Results: Median age was 48 years (range 9-72). Median follow-up (range) for all patients was 2.2 (0.0-15.1) years and for patients alive at the time of last follow-up (n=58), 6.3 (3.0-8.3) years. Mean organ doses in Gy were lung 7.1, kidneys 6.7, thyroid 6.8, and lens 2.5. The cumulative incidence of radiation pneumonitis (RP) was 0.5%. The cumulative incidence of infection and RP (I/RP) was 35.4% (95%CI: 24.9-46.1%). Mean lung dose <8 Gy predicted for numerically lower cumulative rates of I/RP (30.5% vs 51.0%, P=.10). No radiation-induced renal toxicity was noted. Cumulative incidence of elevated TSH was 16.5% (95%CI: 8.2-27.4%) with 14.1% (95%CI: 6.0-25.5%) requiring replacement therapy. Cumulative incidence of cataract formation was 25% (95%CI: 13.5-39.0%) with 12.0% (95%CI: 4.6-23.2%) requiring surgery.

Conclusion: To our knowledge, this represents the largest study to date reporting long term toxicities after TMI/TMLI. TMI/TMLI is associated with lower rates of pulmonary toxicity, renal toxicity, and hypothyroidism compared with historical cohorts treated with conventional total body irradiation. Rates of cataract formation were comparable. This study supports continued evaluation of TMI/TMLI conditioning regimens in patients undergoing HCT.