Date Printed: May 27, 2018: 07:28 PM

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Original Effective Date: 01/15/13

Reviewed: 10/31/17

Revised: 11/15/17

Subject: Extracorporeal Photopheresis


Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
Other References Updates    


Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory procedure that involves the following steps:

  1. Blood is collected into a centrifuge system that separates the leukocyte-rich portion (buffy coat) from the rest of the blood.
  2. The photosensitizer agent 8-methoxypsoralen (8-MOP) is added to the lymphocyte fraction, which is then exposed to ultraviolet (UV) A (320-400 nm wavelength) light at a dose of 1-2 J per square cm.
  3. The light-sensitized lymphocytes are reinfused into the candidate.

ECP has been investigated for the treatment of individuals with a variety of autoimmune diseases, graft-versus-host disease (GVHD), and cutaneous T-cell lymphoma (CTCL), as well as treatment for and prevention of organ rejection after solid-organ transplant, and other miscellaneous conditions.

Treatment of Graft-versus-Host Disease (GVHD)

ECP as a treatment of GVHD after a prior allogeneic stem-cell transplant is based on the fact that GVHD is an immunologically mediated disease. GVHD can be categorized into acute disease, occurring within the first 100 days after infusion of allogeneic cells, or chronic disease, which develops sometime after 100 days. Acute GVHD is commonly graded from I–IV, ranging from mild disease, which is characterized by a skin rash without involvement of the liver or gut, to grades III and IV, which are characterized by generalized erythroderma, elevated bilirubin levels, or diarrhea. Grade III acute GVHD is considered severe, while grade IV is considered life-threatening. Chronic GVHD typically presents with more diverse symptomatology resembling autoimmune diseases such as progressive systemic sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. Chronic GVHD may affect the mouth, eyes, respiratory tract, musculoskeletal system, and peripheral nerves, as well as the skin, liver, or gut—the usual sites of acute GVHD.

Treatment for and Prevention of Organ Rejection after Solid-Organ Transplant

The standard of care for treatment of organ transplant rejection is immunosuppression, with the particular regimen dictated by the organ being transplanted. As organ transplantation success rates have improved, more individuals are facing the morbidity and mortality associated with immunosuppressive therapies developed to prevent rejection of the transplanted organ. Immunosuppressive therapies are used to lower the responsiveness of the recipient’s immune system, decreasing the chance of rejection. Unfortunately, portions of the immune system responsible for the prevention of viral, fungal, and bacterial infection are also affected. This can, in turn, lead to serious infections, including opportunistic infections.

Treatment of Cutaneous T-Cell Lymphoma (CTCL)

According to the National Cancer Institute (NCI), CTCL is a neoplasia of malignant T lymphocytes that initially present as skin involvement. CTCL is extremely rare, with an estimated incidence of approximately 0.4 per 100,000 annually but, because most are low-grade malignancies with long survival, the overall prevalence is much higher. Two CTCL variants, mycosis fungoides and the Sezary syndrome, account for approximately 60% and 5% of new cases of CTCL, respectively.

CTCL is included in the Revised European-American Lymphoma classification as a group of low-grade T-cell lymphomas, which should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large-cell lymphoma, peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma. In addition, a number of benign or very indolent conditions can be confused with mycosis fungoides, further complicating diagnosis.

Mycosis fungoides typically progresses from an eczematous patch/plaque stage, covering less than 10% of the body surface (T1), to a plaque stage, covering 10% or more of the body surface (T2), and finally to tumors (T3) that frequently undergo necrotic ulceration. Sezary syndrome is an advanced form of mycosis fungoides with generalized erythroderma (T4) and peripheral blood involvement (B1) at presentation. Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma sometimes occurs during the course of these diseases and is associated with a poor prognosis. A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staphylococcus species and subsequent systemic infections.

Appropriate therapy of CTCL depends on a variety of factors, including stage, the individual’s overall health, and the presence of symptoms. In general, therapies can be categorized into topical and systemic treatments that include ECP. In contrast to more conventional lymphomas, CTCL, possibly excepting ones in the earliest stages, is not curable. Thus, systemic cytotoxic chemotherapy is avoided except for advanced stage cases. Partial or complete remission is achievable, although most require lifelong treatment and monitoring.

Treatment of Autoimmune Disease

The use of ECP as a treatment of autoimmune disease is based on the premise that pathogenic lymphocytes form an expanded clone of cells, which are damaged when exposed to UV light in the presence of 8-MOP. It is hypothesized that the resulting damage induces a population of circulating suppressor T cells targeted against the light-damaged cells. It is further hypothesized that these suppressor T cells are targeted at a component of the cell that is common to the entire clone of abnormal cells (i.e., not just the light-sensitized cells), thus inducing a systemic effect. However, although scleroderma and other autoimmune diseases are associated with the presence of circulating antibodies, it is not certain how these antibodies are related to the pathogenesis of the disease.


Acute Graft-Versus-Host Disease

Extracorporeal photopheresis meets the definition of medical necessity as a technique to treat acute graft-versus-host disease that is refractory to medical therapy.

Extracorporeal photopheresis is considered experimental or investigational as a technique to treat acute graft-versus-host disease that is either previously untreated or is responding to established therapies.

Chronic Graft-Versus-Host Disease

Extracorporeal photopheresis meets the definition of medical necessity as a technique to treat chronic GVHD that is refractory to medical therapy.

Extracorporeal photopheresis is considered experimental or investigational as a technique to treat chronic GVHD that is either previously untreated or is responding to established therapies.

Organ Rejection after Solid-Organ Transplant

Extracorporeal photopheresis meets the definition of medical necessity to treat cardiac allograft rejection, including acute rejection, that is either recurrent or that is refractory to standard immunosuppressive drug treatment.

Extracorporeal photopheresis is considered experimental or investigational for all other indications related to treatment or prevention of rejection in solid-organ transplantation.

Cutaneous T-cell Lymphoma

Extracorporeal photopheresis meets the definition of medical necessity as a technique to treat:

Extracorporeal photopheresis is considered experimental or investigational as a technique to treat early stage (I/II) cutaneous T-cell lymphoma that is either previously untreated or is responding to established non-systemic therapies.

Autoimmune Diseases

Extracorporeal photopheresis is considered experimental or investigational as a technique to treat either the cutaneous or visceral manifestations of autoimmune diseases, including but not limited to scleroderma, systemic lupus erythematosus, rheumatoid arthritis, pemphigus, psoriasis, multiple sclerosis, diabetes, or autoimmune bullous disorders, severe atopic dermatitis, or Crohn’s disease.


The use of extracorporeal photopheresis for all other indications is considered experimental or investigational. The clinical evidence in peer-reviewed literature is insufficient to permit conclusions on efficacy and net health outcomes for indications other than those noted above.


CPT Coding:


Photopheresis, extracorporeal

ICD-10 Diagnoses Codes That Support Medical Necessity:

C84.00 – C84.09

Mycosis fungoides

C84.10 – C84.19

Sezary’s disease

D89.810 – D89.813

Graft-versus-host disease

T86.00 – T86.09

Complications of bone marrow transplant

T86.21 – T86.22

Heart transplant rejection or failure


Cardiac allograft vasculopathy


Refer to section entitled POSITION STATEMENT.


Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage:

The following National Coverage Determination (NCD) was reviewed on the last guideline reviewed date: Extracorporeal Photopheresis (110.4) located at


Autoimmune disease: when the body’s immune system attacks the cells it is supposed to protect. This is a heterogeneous group of immune-mediated disorders, with some of the most common types being multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis/scleroderma.

Graft-versus host disease (GVHD): a rare disorder that can strike persons whose immune system is deficient or suppressed and who have received a bone marrow transplant or a non-irradiated blood transfusion. Symptoms may include skin rash, intestinal problems and liver dysfunction.

Cutaneous T-cell lymphoma (CTCL): a group of disorders characterized by abnormal accumulation of malignant T-cells in the skin, potentially resulting in the development of rashes, plaques and tumors. CTCLs belong to a larger group of disorders known as non-Hodgkin's lymphomas (NHLs).


None applicable.


Index terms:

Note: The use of specific product names is illustrative 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.

Extracorporeal photochemotherapy
UVAR® XTS Photopheresis System


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  2. Agency for Healthcare Research and Quality (AHRQ). Guideline Summary NGC-9104: Diagnosis and management of chronic graft-versus-host disease. Haemato-oncology Task Force of the British Committee. Br J Haematol. 2012 Jul;158(1):46-61.
  3. Agency for Healthcare Research and Quality (AHRQ). Guideline Summary NGC-9106. Organ-specific management and supportive care in chronic graft-versus-host disease. British Committee for Standards in Haematology - British Society of Blood and Marrow Transplantation. Br J Haematol 2012 Jul;158(1):62-78.
  4. Agency for Healthcare Research and Quality (AHRQ). Guideline Summary NGC-10034: Extra-corporeal photopheresis in the management of graft-versus-host disease in patients who have received allogeneic blood or bone marrow transplants: recommendations. Stem Cell Transplant Steering Committee. Toronto (ON): Cancer Care Ontario (CCO); 2013 Aug 29.
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  8. Blue Cross Blue Shield Association Medical Policy Reference Manual. 8.01.36, Extracorporeal Photopheresis after Solid-Organ Transplant and for Graft-versus-Host Disease, Autoimmune Disease, and Cutaneous T-Cell Lymphoma. April 2015.
  9. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Extracorporeal photopheresis for autoimmune disease. TEC Assessments 2001; Volume 16, Tab 10.
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  12. Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Extracorporeal Photopheresis (110.4). 04/30/12.
  13. NCT00054600. Safety and Efficacy Study of Photopheresis With UVADEX to Prevent Graft-versus-Host Disease. Therakos: last updated 04/07/10.
  14. NCT00157001. Feasibility Study of Photopheresis Post Angioplasty. Therakos: last updated 03/29/11.
  15. NCT00609609. Photopheresis for the Treatment of Acute Graft Versus Host Disease. M.D. Anderson Cancer Center: last updated 09/06/12.
  16. NCT01174940. Test Extracorporeal Photopheresis (ECP) Treatment Before/After Allogeneic Bone Marrow Transplant (BMT) or Peripheral Blood Stem Cell (PBSC) Transplant to Prevent Graft Versus Host Disease. University of Kansas: last updated 08/14/12.
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  42. Robinson CA, et al. Cessation of extracorporeal photopheresis in chronic lung allograft dysfunction: effects on clinical outcome in adults. Swiss Med Wkly. 2017 May 10;147:w14429.
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  47. U.S. Food and Drug Administration, UVAR XTS PHOTOPHERESIS SYSTEM- P860003 S047 (02/01/08); THERAKOS UVAR XTS PHOTOPHERESIS SYSTEM- P860003 S049; UVAR XTS PHOTOPHERESIS SYSTEM- P860003 S050.
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This Medical Coverage Guideline (MCG) was approved by the BCBSF Medical Policy & Coverage Committee on 10/31/17.



New Medical Coverage Guideline.


Scheduled review. Revised description, program exceptions section and index terms. Updated references.


Scheduled review. Revised position statement, description section and index terms. Updated references.


Revision; updated ICD10 coding section.


Scheduled review. Position statement maintained. Updated references.


Revision: ICD-9 Codes deleted.


Scheduled review. Position statement maintained. Revised ICD10 coding section. Updated references.


Scheduled review. Position statement maintained. Updated references.

Date Printed: May 27, 2018: 07:28 PM