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Medical Policy Bulletin
Title:Stem-Cell Therapy for Orthopedic Applications and Autologous Platelet-Derived Growth Factors (PDGFs)/Platelet-Rich Plasmas (PRPs) for Acute or Chronic Wound Healing and Other Miscellaneous Conditions
Policy #:07.07.09e


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.


Intent
The intent of this policy is to communicate that stem-cell therapy for orthopedic applications and autologous platelet-derived growth factors (PDGFs)/platelet-rich plasmas PRPs) for the treatment of acute or chronic wound healing and other miscellaneous conditions (including as an adjunct to surgical procedures) are considered experimental/investigational (E/I).

Services that are considered experimental/investigational are noncovered services. However, routine services associated with some experimental/investigational services may be covered when they are performed in a qualified clinical trial. For more information, refer to the Company policy on qualifying clinical trials.

For information on policies related to this topic, refer to the Cross References section in this policy.

    Description
    STEM-CELL THERAPY FOR ORTHOPEDIC APPLICATIONS

    Mesenchymal stem cells (MSCs) are multipotent stem cells (also referred to as stromal multipotent cells) that are able to differentiate into a variety of tissue types, including organs, trabecular bones, tendons, articular cartilages, ligaments, muscles, fats, and various musculoskeletal tissues. MSCs have possible orthopedic applications, which include the treatment of damaged bones, cartilages, ligaments, tendons, and intervertebral discs.

    MSCs decrease as people age, and acute and chronic illnesses and diseases can tax stem-cell reserves. MSCs can be increased and stem-cell reserves replenished by treatment with drugs such as filgrastim injection (Neupogen®) and plerixafor injection (Mozobil®) to mobilize stem cells, or by autologous stem-cell transplantation. Although MSCs can be harvested from the bone marrow, harvesting requires an additional procedure that may result in donor site morbidity.

    Tissues such as muscle, cartilage, tendon, ligaments, and vertebral discs show limited capacity for endogenous repair (i.e., the repair of cells within their own structures). Therefore, tissue engineering techniques have been developed to improve the efficiency of repair or regeneration of damaged musculoskeletal tissues. Using an engineered process to induce cell division and differentiation, without adverse effects such as the formation of neoplasms, remains a challenge.

    According to the US Food and Drug Administration (FDA), "...Cell-based therapy is one of the most rapidly advancing approaches intended to repair, replace, restore, or regenerate cells, tissues, and organs. The cell-based therapies use immature stem cells that are expanded outside the body. The expanded cells are sometimes used in their immature state, but are often manufactured into mature cells before being used. Manufacturing a large number of cells outside the natural environment of the body may lead to ineffective or dangerous cells. It is important to control the production process and to define measures that reliably predict safety and efficacy of the cell-based products."

    No products using engineered MSCs have been approved by the FDA for orthopedic applications. The FDA has determined that MSCs sold by Regenerative Sciences for use in the RegenexxTM Procedure (Regenerative Sciences, Colorado) would be considered drugs or biological products and thus require submission for a New Drug Application (NDA) or a Biologics Licensing Application (BLA) to the FDA. These procedures by Regenexx TM have platelet-derived components as well.

    The literature overall suggests that this technology is in the early stages of development. Preliminary testing of tissue engineering has focused on animal models. Several clinical trials are in progress but are not expected to be completed for several years. Current information on procedures using autologous bone marrow derived from MSCs for orthopedic applications in humans consists mainly of case reports or case series with insufficient data to evaluate health outcomes. Therefore, the use of stem cells for orthopedic applications remains under investigation.

    The American Association of Orthopaedic Surgeons (AAOS) states that stem-cell procedures in orthopedics are still at an experimental stage; most musculoskeletal treatments using stem cells are performed at research centers as part of controlled clinical trials.


    AUTOLOGOUS PLATELET-DERIVED GROWTH FACTORS (PDGFs)/PLATELET-RICH PLASMAS (PRPs)

    Impaired wound healing may be caused by venous stasis, peripheral neuropathy, ischemia, or a poor healing response related to local trauma. These clinical conditions are often present in individuals with diabetes. Current treatment of chronic, non-healing wounds includes debridement, management of infection, limitation of weight-bearing activities, and revascularization of the affected area.

    The science of wound healing is advancing rapidly due to new therapeutic approaches such as the use of growth factors. Several growth factors contribute to wound healing, including platelet-derived growth factors (PDGFs)/platelet-rich plasmas (PRPs), epidermal growth factors, fibroblast growth factors, transforming growth factors, and insulin-like growth factors. Topically applied PDGFs/PRPs have been evaluated as primary clinical agents to help promote wound healing.

    PDGFs/PRPs have also been proposed for conditions such as epicondylitis (tennis elbow) and plantar fasciitis (an inflammatory condition that causes intense heel pain), and have been investigated as adjuncts to periodontal, reconstructive, and orthopedic surgical procedures.

    PDGFs/PRPs are autologous platelet concentrations suspended in plasma and can be prepared from samples of centrifuged autologous blood. Exposure to solutions of thrombin and calcium chloride degranulates platelets, causing the release of the growth factors, which results in a polymerization of fibrin from fibrinogen and the creation of a platelet gel. Because autologous PDGFs/PRPs originate from the individual's own blood, they are not regulated by the US FDA.

    Procuren ® (Cytomedix Inc.), a type of PDGF/PRP, has not been marketed since 2002. AutoloGel ™ (Cytomedix Inc.) and SafeBlood ® (SafeBlood Technologies) are similar, yet distinct, autologous PDGF/PRP products that are currently marketed for wound healing. Both products centrifuge blood samples from an individual to create PDGF/PRP, which is then activated by various reagents. The resultant gel-like substance (AutoloGel™) or semi-solid graft (SafeBlood®) can then be immediately applied to a wound or used as an adjunct to surgery to promote hemostasis and accelerate healing. Unlike Procuren®, which requires processing at a specialty laboratory, AutoloGel™ and SafeBlood® can be prepared on-site using proprietary portable centrifuges and may therefore be used in wound care clinics, home settings, skilled nursing facilities, and acute care facilities.

    The Magellan ®, Autologous Platelet Separator System (Arteriocyte Medical Systems) is a portable centrifuge approved by the FDA in June 2003. The Magellan® system can be used in the clinical laboratory or intraoperatively for rapid preparation of platelet-poor plasma and platelet concentrate (PDGF/PRP). The PDGF/PRP is prepared from a very small amount of blood that is mixed with autograft and/or allograft bone before its application to an orthopedic site.

    At present, there is insufficient published medical literature to support the clinical safety and/or effectiveness of autologous platelet-derived products to promote the healing of chronic, non-healing wounds, or for use with other miscellaneous conditions.

    The possible benefit of using PDGF/PRP is of considerable interest. There is limited but rapidly developing literature on the safety and effectiveness of PRP, in addition to an increasing number of routine clinical trials in progress involving various conditions. However, clear evidence of PRP benefit is still lacking, and the safety and effectiveness of PDGF/PRP for treatment of acute or chronic wounds, or as an adjunct to surgical procedures, remain to be proven.

    Policy
    Stem-cell therapy, alone or in combination with platelet-derived products (e.g., plasma, lysate), for orthopedic applications is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.

    The use of autologous platelet-derived growth factors (PDGFs)/platelet-rich plasmas (PRPs) for the treatment of acute or chronic wound healing and other miscellaneous conditions (including as an adjunct to surgical procedures) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.


    BILLING GUIDELINES

    Per CPT Guidelines, CPT Code: 20926 does not represent platelet-rich plasma injections.

    To report platelet-rich plasma (PRP) injections, professional providers must use CPT 0232T.

    Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

    Guidelines
    BENEFIT APPLICATION

    Subject to the terms and conditions of the applicable benefit contract, the use of stem-cell therapy for orthopedic applications and autologous platelet-derived growth factors (PDGFs)/platelet-rich plasmas (PRPs) for the treatment of acute or chronic wound healing and other miscellaneous conditions (including as an adjunct to surgical procedures) are not eligible for payment under the medical benefits of the Company’s products because these services are considered experimental/investigational and, therefore, not covered. Services that are experimental/investigational are a benefit contract exclusion for all products of the Company.

    MEDICARE

    This policy is consistent with Medicare's coverage determination for the treatment of chronic non-healing wounds.

    There is no Medicare coverage determination for stem-cell therapy for orthopedic applications or for PDGFs/PRPs for treatment of acute wounds or as an adjunct to a surgical procedure; therefore, the Company policy is applicable.

    US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

    PDGFs/PRPs originate from an individual's own blood; therefore, they are not generally regulated by the US Food and Drug Administration (FDA). However, the FDA may consider some products to fall under drugs or biologics and thus require submission for a New Drug Application (NDA) or a Biologics Licensing Application (BLA) to the FDA.

    References
    American Academy of Orthopaedic Surgeons. Stem cells and orthopaedics. Your Orthopaedic Connection 2007; Available at: http://orthoinfo.aaos.org/topic.cfm?topic=A00501. Accessed on July 25, 2013.

    Bauer SR; US Food and Drug Administration. Assuring safety and efficacy of stem-cell based products. Available at: http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/BiologicsResearchAreas/ucm127182.htm. Accessed on July 25, 2013.

    Centeno CJ, Schultz JR, Cheever M, et al. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther.2010;5(1):81-93.

    Centeno CJ, Schultz JR, Cheever M, et al. Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther. 2011 Dec;6(4):368-78.

    Centers for Medicare & Medicaid Services (CMS). Decision memo for autologous blood-derived products for chronic non-healing wounds (CAG-00190N). [CMS Web site]. 12/15/03. Available at: http://www.cms.gov/mcd/viewdecisionmemo.asp?id=95. Accessed on July 25, 2013.

    Centers for Medicare and Medicaid Services (CMS). National Coverage Determination (NCD). 270.3: Blood-derived products for non-healing wounds. [CMS Web site]. Original: 12/28/92. (Revised: 8/2/2012). Available at:http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=270.3&ncd_version=4&basket=ncd%3A270%2E3%3A4%3ABlood%2DDerived+Products+for+Chronic+Non%2DHealing+Wounds. Accessed on July 25, 2013.

    Crovetti G, Martinelli G, Issi M, et al. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004;30(2):145-151.

    Deans TL, Elisseeff JH. Stem cells in musculoskeletal engineered tissue. Curr Opin Biotechnol. 2009;20(5):537-544.

    Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: Implications for wound healing. Plast Reconstr Surg.2004;114(6):1502-1508.

    Floryan KM, Berghoff WJ. Intraoperative use of autologous platelet-rich and platelet-poor plasma for orthopedic surgery patients. AORN J. 2004;80(4):667-678.

    Freedman BM, Oplinger EH, Freedman IS. Topical becaplermin improves outcomes in work-related fingertip injuries. J Trauma. 2005;59(4):956-958.

    Glover JL, Weingarten MS, Buchbinder DS, et al. A 4-year outcome-based retrospective study of wound healing and limb salvage in patients with chronic wounds. Adv Wound Care. 1997;10(1):33-38.

    Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. J Extra Corpor Technol. 2004;36(1):28-35.

    Margolis DJ, Bartus C, Hoffstad O, et al. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Wound Repair Regen. 2005;13(6):531-536.

    Margolis DJ, Kantor J, Santanna J, et al. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care. 2001;24(3):483-488.

    McAleer JP, Kaplan E, Persich G. Efficacy of concentrated autologous platelet-derived growth factors in chronic lower-extremity wounds. J Am Podiatr Med Assoc. 2006;96(6):482-488.

    Niezgoda JA, Van Gils CC, Frykberg RG, Hodde JP. Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers. Adv Skin Wound Care.
    2005;18(5 pt 1):258-266.

    SafeBlood® Technologies. Overview of the autologous platelet grafting. The need and the market approach. [SafeBlood® Technologies Web site]. Available at:
    http://www.safebloodtech.com/platelet.asp. Accessed on July 25, 2013.

    Senet P, Bon FX, Benbunan M, et al. Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers. J Vasc Surg. 2003;38(6):1342-1348.

    Stacey MC, Mata SD, Trengove NJ, Mather CA. Randomized double-blind placebo controlled trial of topical autologous platelet lysate in venous ulcer healing. Eur J Vasc Endovasc Surg. 2000;20(3):296-301.

    US Food and Drug Administration (FDA). Center for Devices and Radiological Health. MagellanTM Autologous Platelet Separator System. 510(k) summary. [FDA Web site]. June 2003. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/SubstantiallyEquivalent510kDeviceInformation/UCM081422.pdf. Accessed on July 25, 2013.

    US Food and Drug Administration. Untitled letter. Guidance, compliance, and regulatory information (Biologics) 2008; Available online at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm. Accessed on July 25, 2013.

    Wakitani S, Imoto K, Yamamoto T, et al. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10(3):199-206.

    Wakitani S, Nawata M, Tensho K, et al. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007;1(1):74-9.

      Coding Table

      Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

      The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

      In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

      The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

      Code SystemCode Number(s) and Narrative(s)
      CPTPLEASE REPORT THE FOLLOWING CODE FOR PLATELET-RICH PLASMA (PRP):

      0232T


      The following CPT codes are not specific to the service(s) described within this policy. However, they are considered experimental/investigational and therefore not covered, when used to represent stem-cell therapy for orthopedic applications.

      38206, 38232, 38241
      ICD-10-PCS codes will be in effect on the determined ICD-10 compliance date. However, they are being added to policy for informational purposes only.
      ICD - 9 ProcedureN/A
      ICD - 10 Procedure N/A
      ICD-10-CM codes will be in effect on the determined ICD-10 compliance date. However, they are being added to policy for informational purposes only.
      ICD - 9 DiagnosisThe use of stem-cell therapy for orthopedic applications and autologous platelet-derived growth factors (platelet-rich plasma) for acute or chronic wound healing and other miscellaneous conditions is considered experimental/investigational for all diagnoses.
      ICD - 10 DiagnosisN/A
      HCPCS Level IIG0460: Autologous platelet rich plasma for chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures and administration, per treatment

      S9055: Procuren or other growth factor preparation to promote wound healing
      Revenue CodesN/A

      Cross References





      Version Effective Date: 07/01/2013


      The Policy Bulletins on this web site were developed to assist Independence Blue Cross and its subsidiaries ("IBC") in administering the provisions of the respective benefit programs, and do not constitute a contract. If you are an IBC member, please refer to your specific benefit program for the terms, conditions, limitations and exclusions of your coverage. IBC does not provide health care services, medical advice or treatment, or guarantee the outcome or results of any medical services/treatments. The facility and professional providers are responsible for providing medical advice and treatment. Facility and professional providers are independent contractors and are not employees or agents of IBC. If you have a specific medical condition, please consult with your doctor. IBC reserves the right at any time to change or update its Policy Bulletins. ©2015 Independence Blue Cross. All Rights Reserved.  Current Procedural Terminology ©2015 American Medical Association. All Rights Reserved.