Bone marrow vascular architecture: Implications for targeting bone marrow cancers.

Abstract

e18610 Background: Many hematologic cancers (HC) are localized in the bone marrow (BM). Drug therapies are often administered intravenously (IVT) and require doses that limit serious adverse side effects (SAE) but which also compromise tumor control. An underappreciated question is whether advances in therapy delivery modes could dispatch more to the BM target than IVT while limiting SAE. Methods: Academic sources on the anatomy/physiology of BM extra (EXO) and intraosseous (INO) blood flow (BF) were analyzed from medical textbooks + published literature from multiple specialties. The outcomes + SAEs of interventional techniques in high mortality diseases were also evaluated. Results: The BM of all bones are potential reservoirs for tumor cells. 5 L/Min cardiac output (CO) distributes unequally to all organs. Bone and BM receive 5% of CO divided among 206 bones by size. BM vascular density is robust/diffuse, hence only a few BM vessels deliver drugs primarily to the target. Anatomic/physiologic factors also affect EXO/ INO BF in normal/disease states: vasomotor tone, blood pressure, vascular resistance/permeability, intramedullary pressure, endothelial function, angiogenesis, microvascular anatomy/density. Understanding a detailed architecture of the EXO/INO BM blood supply (BS) may help conceptually. General categories of bones are: long, flat, irregular, short, sesamoid. EXO flow comes from local systemic arteries. INO arteries consist of nutrient, periosteal, metaphyseal and transcortical vessels which are distributed variably in the 5 bone classes. These vessels eventually lead to dense diffuse capillary systems which deliver drugs thoughout the BM, only small amounts directed to the more localized target, Venous drainage generally accompanies the arteries. Knowledge of the EXO/INO vascular layout addresses the feasibility of direct and regional arterial delivery (IADT) to the BM. Safety of arterial procedures is denoted by the SAE/efficacy of transcatheter aortic valve replacement (TAVR) in cancer patients including HC. 30 day mortality of cancer/noncancer classes is similar as are vascular complications. IADT to solid tumors (ST) retrospectively has inferred short term positive tumor responses + fewer SAE than IVT. The pharmacokinetics (PK) are more efficacious than IVT. Conclusions: IVT to tumors within BM is reduced by BM %CO, dispersal of BF to bones, dense BM vasculature and vascular physiologic factors. No matter how effective therapy is against tumors during testing, if only a small portion reaches the tumor niche effectiveness may be undermined. Interventionalists can offer short term direct and indirect regional IADT to major blood vessels supplying the BM as a conditioning protocol with improved local BM delivery, followed by IV therapy. The results of IADT in ST has been encouraging regarding benefits/SAE. It should also be evaluated for HC with PK studies, evolving from there based on the results.