Peripheral arterial disease (PAD) is a common atherosclerotic syndrome associated with significant morbidity and mortality. Development of PAD is characterized by narrowing and occlusion of arterial vessels and eventual reduction in distal perfusion. Critical limb ischemia is the end stage of lower-extremity PAD in which severe obstruction of blood flow results in ischemic pain at rest, ulcers, and a significant risk for limb loss. The standard therapy for severe, limb-threatening ischemia is revascularization aiming to improve blood flow to the affected extremity. If revascularization fails or is not possible, amputation is often necessary.
A proposed treatment for critical limb ischemia due to peripheral arterial disease is stem cell therapy. The rationale of hematopoietic cell/bone marrow-cell therapy in PAD is to induce arteriogenesis by boosting the physiologic repair processes. This requires large numbers of functionally active autologous precursor cells and, subsequently, a large quantity of bone marrow or other source of stem cells. The concentrate of bone marrow aspirate contains a mix of cell types, including lymphocytoid cells, erythroblasts, monocytoid cells and granulocytes. Following isolation and concentration, the hematopoietic cell/bone marrow concentrate is administered either intra-arterially or through multiple injections into the muscle.
Treatment of peripheral arterial disease, including critical limb ischemia, with injection or infusion of stem cells concentrated from bone marrow aspirate is considered investigational.
Policies with similar titles:
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
The current literature on stem cells as a treatment for critical limb ischemia due to PAD consists primarily of phase 2 studies using various cell preparation methods and methods of administration. A meta-analysis of the trials with the lowest risk of bias has shown no significant benefit of stem cell therapy for overall survival, amputation-free survival, or amputation rates. Well-designed randomized controlled trials with a larger number of subjects and low risk of bias are needed to evaluate the health outcomes of these various procedures. More data on the safety and durability of these treatments are also needed. The evidence is insufficient to determine the effects of the technology on health outcomes.
BlueCross BlueShield Association. Medical Policy Reference Manual. (7:2017). Stem cell therapy for peripheral arterial disease (8.01.55). Retrieved December 18, 2017 from BlueWeb. (18 articles and/or guidelines reviewed)
Botham, C., Bennett, W., and Cooke, J. (2013). Clinical trials of adult stem cell therapy for peripheral artery disease. Methodist Debakey Cardiovasc Journal, 9 (4), 201-205. (Level 2 evidence)
European Society of Cardiology. (2011). ESC guidelines on the diagnosis and treatment of peripheral artery diseases. Retrieved February 26, 2016 from http://eurheartj.oxfordjournals.org.
Franz, R., Shah, K., Pin, R., Hankins, T., Hartman, J., & Wright, M. (2015). Autologous bone marrow mononuclear cell implantation therapy is an effective limb salvage strategy for patients with severe peripheral arterial disease. Journal of Vascular Surgery, 62 (3), 673-680. Abstract retrieved February 26, 2016 from PubMed database.
Peeters Weem, S., Teraa, M., de Borst, G., Verhaar, M., & Moll, F. (2015). Bone marrow derived cell therapy in critical limb ischemia: a meta-analysis of randomized placebo controlled trials. European Journal of Vascular and Endovascular Surgery, 50 (6), 775-783. Abstract retrieved February 26, 2016 from PubMed database.
Qadura, M., Terenzi, D.C., Verma, S., Al-Omran, M., & Hess, D.A. (2017). Cell therapy for critical limb ischemia: an integrated review of pre-clinical and clinical studies. Stem Cells, 2017 Dec 11. Doi:10.1002/stem.2751. [Epub ahead of print]. Abstract retrieved December 18, 2017 from PubMed database.
Ravel, Z. & Losordo, D. (2013). Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circulatory Research, 112 (9), doi:10.1161/CIRCRESAHA.113.300565. (Level 1 evidence)
Rigato, M., Monami, M., & Fadini, G.P. (2017). Autologous cell therapy for peripheral arterial disease: systematic review and meta-analysis of randomized, nonrandomized, and noncontrolled studies. Circulation Research, 120 (8), 1326-1340. Abstract retrieved December 18, 2017 from PubMed database.
Tournois, C., Pignon, B., Sevestre, M.A., Al-Rifai, R., Creuza, V., Poitevin, G., et al. (2017). Cell therapy in critical limb ischemia: a comprehensive analysis of two cell therapy products. Cytotherapy, 19 (2), 299-310. Abstract retrieved December 18, 2017 from PubMed database.
U. S. Food and Drug Administration. (2002, October). Center for Devices and Radiological Health. Pre-market approval decisions K071934 (MarrowStim™). Retrieved January 20, 2017 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2010, December). Center for Devices and Radiological Health. Pre-market approval decisions K10334 (SmartPRep®). Retrieved July 14, 2011 from http://www.accessdata.fda.gov.
ORIGINAL EFFECTIVE DATE: 12/10/2011
MOST RECENT REVIEW DATE: 3/8/2018
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.