1096 - Multimodal Imaging of the Functional and Physiological Bone Marrow Microenvironment in AML: Toward Personalized Clinical Applications
Presenter(s)
S. K. Hui1, M. Al Malki2, H. Ghimire1, C. Han1, J. F. Sanchez2, D. Yang3, M. Malekzadeh4, S. Mokhtari2, B. Chen5, J. Song6, S. V. Dandapani1, R. Nakamura2, A. Salhotra2, A. Stein2, and J. Y. C. Wong1; 1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, 3Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, 4City of Hope, Duarte, CA, 5Department of Diagnostic Radiology, City of Hope, Duarte, CA, 6Department of Pathology, City of Hope, Duarte, CA
Purpose/Objective(s): Relapse remains a major barrier to long-term survival in relapsed/refractory AML/ALL post-HCT. Our prior studies demonstrated that dose-escalated total marrow and lymphoid irradiation (TMLI, 16–20 Gy at 1.5–2 Gy BID), which targets radiation to the bone marrow (BM) and lymph nodes, is safe and improves overall survival compared to standard total body irradiation (TBI). However, reducing relapse while preserving the bone marrow microenvironment (BME) remains an unmet need. This NIH-funded clinical correlative study (NCT03422731) integrates F-18 fluorothymidine (FLT) -PET/CT, dual-energy CT (DECT), and water-fat MRI (wfMRI) to globally map functional (cell proliferation) and physiological (marrow fat/active marrow) BME globally in patients with active AML and in CR. Given AML’s radiosensitivity, we explored image-guided TMLI with simultaneous boost (SIB) to active BM niches and evaluated wfMRI/DECT-derived fat fraction (FF%) as biomarkers for BM regeneration and engraftment dynamics.
Materials/Methods: AML patients from two trials (NCT02094794, NCT03494569) underwent FLT-PET (n=25), DECT (n=22), and wfMRI (n=22) before and after HCT. Patients receiving TMLI were compared to a CR cohort treated with TBI (12–13.2 Gy at 1.65–2 Gy BID). FLT-PET measured standardized uptake values (SUVs) across skeletal regions; DECT and wfMRI quantified FF% in the spine and iliac crest, validated with biopsies. Longitudinal imaging assessed BME recovery over one year. Functional TMLI planning simulated SIB to FLT-avid regions, evaluating dose conformity and organ-at-risk (OAR) sparing (detailed dosimetry reported separately).
Results: FLT-PET distinguished AML marrow from remission at one year, with significantly higher SUVmean (13.2 vs. 6.6; p=0.02; 9.6 vs 4.5, p=0.03) for spine and pelvis respectively. FF% (n=32) inversely correlated with cellularity% in biopsy findings (Pearson r = - 0.61; p<0.001). DECT and wfMRI demonstrated progressive marrow recovery post-TMLI, with FF% normalizing at one year, comparable to TBI-treated patients. SIB-TMLI simulations confirmed safe dose escalation to 24 Gy while meeting OAR limits (mean lung =7.7 Gy; bowel <6 Gy).
Conclusion: Integrating FLT-PET, DECT, and wfMRI provides a comprehensive approach to assess BME in AML patients undergoing TMLI. FF% serves as a biomarker for BM regeneration, reflecting a dynamic, adaptable BME tolerating higher radiation doses. A strong inverse correlation between FLT SUV and FF% suggest leukemic burden resides in active marrow niches. Multimodal imaging-guided SIB-TMLI allows high precision and personalized dose escalation to disease-rich marrow while sparing OARs, benefitting older or high-risk patients. These findings underscore BME preservation’s importance in AML treatment and support adaptive, image-guided therapies to improve outcomes.