B. R. Perez1, G. Rajeev-Kumar1, M. Tran2, J. Partouche1, W. Stock2, R. Larson2, S. Kosuri2, J. LaBelle3, J. Kline2, P. Riedell2, M. Bishop2, B. Aydogan1, H. Liu4, and Y. Hasan1; 1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, 2Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, 3Department of Pediatrics, Section of Hematology, University of Chicago Medical Center, Chicago, Chicago, IL, 4Department of Medicine, Section of Hematology/Oncology at the University of Wisconsin, Madison, WI
Purpose/Objective(s): A secondallogeneic stem cell transplantation (allo-SCT) is an option following relapse after an initial SCT for hematologic malignancies. Conditioning with intensity-modulated total marrow irradiation (IM-TMI) is feasible and shows promise in optimizing the therapeutic ratio. We report on clinical outcomes and to identify IM-TMI dose to the oral cavity that would be associated with lower incidence of mucositis to help guide planning. Materials/
Methods: We conducted a retrospective analysis of patients undergoing second allo-SCT enrolled between Dec 2015 and Nov 2023 on a phase I dose-escalation trial of IM-TMI with fludarabine and melphalan. TMI doses were given twice daily, 1.5 Gy per fraction with total dose of 6, 9, or 12 Gy. The clinical target volume consisted of bones excluding mandible (except in 1 case), arms and lower extremities mid-femur down. We collected baseline patient and treatment characteristics and performed univariate analysis reported as mean (SD) or median [interquartile range]. Logistic regression (LR) was performed to evaluate potential predictors of oral mucositis incidence at 1 week following allo-SCT. Results: Of 31 patients, 18 (58%) were male, predominantly white (83%), with median age of 49 [41, 64]. The mean BMI was 30.62 (22.33) and with a Karnofsky >90 (68%). Majority being treated for AML (74%). Most common disease status at time of 2nd allo-SCT included 1st relapse in 8 (26%) followed by 2nd complete remission in 5 (16.1%), and 3rd complete remission in 4 (13%). TMI dose of 9 Gy was delivered to 15 patients (48%), 12 Gy to 10 (32%), and 6 Gy to 5 (16%). The average dose to the oral cavity was 298.05 cGy (95.7), with the oral cavity receiving on average 32% of the prescribed dose. 16 patients (52%) experienced mucositis within a month following allo-SCT with IM-TMI; 14 occurred within 7 days, half grade 1 and grade 3 toxicities. Pearson correlation showed moderate association between oral cavity dose and mucositis grade at day 7 (r = 0.284). On LR analysis of predictors, the oral cavity mean dose (OR = 1.032) and age (OR = 0.878) were found to be significant predictors of mucositis incidence at day 7 (p=0.04 and p=0.03 respectively). In LR model with oral cavity mean dose and age categorized by the median value, an oral cavity mean dose greater than the median of 264.7 cGy was associated with an OR of 44.8 (p=0.023). 5 of 31 patients (16%) had relapsed, 3 in the bone marrow and 2 with solid masses, at an average of 197 days (77.8) post allo-SCT. At a median follow up of 11 months, 11 patients (36%) were alive. Most common cause of death included persistence/progression of disease in 8 (40%) and infection in 9 patients (45%). Conclusion: Our study adds to the evolving literature on the integration of TMI into conditioning regimens for allo-SCT, specifically in the second transplant setting. Given that the oral cavity mean dose and age are significant predictors of mucositis incidence at day 7, caution must be applied in the delivery of TMI to the oral cavity, specifically in this population.
