DESCRIPTION
Peripheral arterial disease (PAD) is a common atherosclerotic syndrome characterized by narrowing occlusion of the arterial vessels and eventual reduction in distal perfusion. Critical limb ischemia is the endstage of PAD of the lower extremities and results in pain at rest, ulcerated skin lesions, and significant risk for limb loss.
Endogenous compensatory mechanisms may occur as a result of occlusive arterial changes. Capillary growth (angiogenesis) mediated by hypoxic changes in the vessels results in the development of small capillaries that sprout from the pre-existing capillary but are too small to compensate for the occlusion of large arteries. Remodeling of collateral arterial vessels (arteriogenesis) is caused by the force exerted on these vessel walls by the blood flow that is redirected away from an occluded vessel. The mechanism underlying arteriogenesis includes the migration of bone marrow-derived stem cells to the perivascular space.
The rationale of hematopoietic stem-cell/bone marrow-cell therapy in PAD is to induce the development of collateral arterial vessels by boosting the physiological repair process of ateriogenesis. This requires large numbers of functionally active autologous precursor cells, and subsequently, a large quantity of bone marrow (e.g., 240-500 mL). Notably, the same risk factors for advanced ischemia (diabetes, smoking, hyperlipidemia and advanced age) are also risk factors for a lower number of circulating stem cells.
POLICY
Treatment of peripheral arterial disease, including critical limb ischemia, with injection or infusion of cells concentrated from bone marrow aspirate is considered investigational.
Policies with similar titles: Progenitor Cell Therapy for the Treatment of Damaged Myocardium Due to Ischemia
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ADDITIONAL INFORMATION
Based on initial evidence from case series and small randomized trials, injection of bone marrow concentrate may hold promise as a treatment for critical limb ischemia due to peripheral arterial disease. However, well-designed and well-conducted randomized controlled trials are needed to evaluate the health outcomes of this procedure. A number of trials are in progress, including several large randomized double-blind placebo controlled trials. Results from these trials are needed to adequately evaluate the impact on net health outcome of this procedure. Further information on the safety and durability of the treatment is also needed.
SOURCES
Aman, B., Luedemann, C., Ratei, R., & Schmidt-Lucke, J.A. (2009). Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplantation, 18 (3), 371-380. (Level 3 Evidence - Independent)
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2011). Stem-cell therapy for peripheral artery disease (8.01.55). Retrieved July 14, 2011 from BlueWeb. (8 articles and/or guidelines reviewed)
Complete Guide to Medicare Coverage Issues [Computer software]. (2011, April). Stem cell transplantation (NCD 110.8.1, p. 2-56). Ingenix.
Fadini, G., Agostini, C., Avogaro, A. (2010). Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis, 209 (1), 10-17. (Level 1 evidence - Independent)
Mantoba, S., Tatsumi, T., Murohara, T., Imaizumi, T., Katsude, Y., Ito, M., et al. (2008). Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. American Heart Journal, 156 (5), 1010 -1018. (Level 3 Evidence - Independent)
U. S. Food and Drug Administration. (2010, December). Center for Devices and Radiological Health. Pre-market approval decisions K103340. Retrieved July 14, 2011 from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=35385.
Walter, D., Krankenberg, H., Balzer, J., Kalka, C. Baumgartner, I., Schlüter, M., et al. (2011). Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebo-controlled pilot trial (PROVASA). Circulation. Cardiovascular Interventions, 4 (1), 26-37. (Level 2 Evidence - Independent)
ORIGINAL EFFECTIVE DATE: 12/10/2011
MOST RECENT REVIEW DATE: 12/10/2011
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