Abstract B29: Increased vertebral marrow adiposity in long-term survivors of pediatric allogeneic hematopoietic stem cell transplant is associated with deficits in trabecular microarchitecture

Abstract

Abstract Background: As treatment-related mortality following allogeneic hematopoietic stem-cell transplantation (alloHSCT) declines, a major unmet need is the identification and prevention of late effects. Long-term survivors of hematologic malignancies requiring alloHSCT show impaired bone density and structure with excess whole body adiposity (Mostoufi-Moab, JBMR, 2012). Marrow adipocytes share common mesenchymal stem cells (MSC) with bone-forming osteoblasts, with an inverse relation between MSC differentiation into osteoblasts or adipocytes. The impact of alloHSCT and total body irradiation (TBI) on marrow adipose tissue (MAT) and trabecular bone microarchitecture (TBA) has not been addressed. Methods: Magnetic resonance spectroscopic imaging (MRSI) and high-resolution structural imaging were used to quantify vertebral MAT and distal tibia TBA on a 1.5 Tesla magnet. Twenty-five alloHSCT recipients with underlying diagnosis of acute leukemia, ages 12-24 years, were enrolled, a median of 11 years (range 5-19) after alloHSCT and TBI, and compared with age-, sex- and race-matched healthy controls. Results: AlloHSCT survivors had lower height Z-scores (-1.39 ± 0.98 vs. -0.04 ± 0.98; p < 0.001), compared with controls, while BMI Z-scores did not differ. Overall, greater MAT was associated with lower bone volume fraction (BVF), R = -0.57, p < 0.001. AlloHSCT was associated with higher mean (± SD) vertebral fat fraction (59.0 ± 11.3 vs. 29.3 ± 9.9; p < 0.001) and trabecular deficits including lower bone volume fraction (β -0.01; 95% CI -0.12, -0.00; p=0.02) and evidence of abnormal microarchitecture [greater erosion (p=0.01) with a more rod like structure (p=0.02)], vs. controls. TBA deficits were more pronounced in female alloHSCT recipients. Growth hormone deficiency was not associated with MAT or bone deficits. Conclusion: Survivors of childhood alloHSCT after TBI demonstrate marked increases in vertebral MAT combined with abnormal trabecular bone microarchitecture. Future studies are needed to determine the metabolic effects and fracture implications of excess MAT, and to identify therapies for improved bone accrual following childhood alloHSCT. Citation Format: Sogol Mostoufi-Moab, Wenli Sun, Jeremy Magland, Elizabeth Isaacoff, Nancy J. Bunin, Jill P. Ginsberg, Felix Wehrli, Justine Shults, Mary B. Leonard. Increased vertebral marrow adiposity in long-term survivors of pediatric allogeneic hematopoietic stem cell transplant is associated with deficits in trabecular microarchitecture. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B29.