CurrentPremera BluecrossPolicy 8.01.36

Extracorporeal Photopheresis

Policy defining medical necessity and investigational indications for extracorporeal photopheresis across organ rejection after solid organ transplant, graft-versus-host disease, cutaneous T-cell lymphoma, autoimmune diseases, and other indications; includes documentation, coding, evidence review, guidelines and trial listings.

Policy Summary

PayerPremera Bluecross

PolicyExtracorporeal Photopheresis

Policy CodePolicy 8.01.36

Change TypeAnnual literature update; clarifications

Effective DateApr. 1, 2026

Next Review Date

Key ActionMedical records must document diagnosis/condition, history and physical documenting severity, and the medical therapy that has been attempted.

SourceLink

POLICY UPDATE CHANGES

Replaced prior policy 8.01.501 with current policy 8.01.36; effective date Apr 1, 2026 and last revised Mar 23, 2026.

Annual review approved December 22, 2025; policy updated with literature review through November 7, 2025; references added. Policy statements unchanged.

Annual review approved March 23, 2026; policy updated with literature review through December 8, 2025; references added. Policy statements unchanged.

Multiple prior annual reviews and updates documented from 2000 through 2026 with literature additions; several reinstatements and coding updates noted (eg, removal of ICD-9/ICD-10 codes from adjudication in 2015).

4Medically Necessary Indications Listed

MultipleInvestigational Indications

36522

Coverage Summary

Policy 8.01.36 (Extracorporeal Photopheresis) is CURRENT and effective 2026-04-01 with last review 2026-03-23. The scope covers ECP use for organ rejection after solid-organ transplant, graft-versus-host disease (GVHD), cutaneous T‑cell lymphoma (CTCL), autoimmune diseases, and other indications, and includes documentation, coding (CPT 36522), evidence review, and guideline references. Coverage stance is mixed: certain indications are listed as medically necessary while most other indications are investigational. Key medically necessary indications include: cardiac allograft rejection when there is acute rejection refractory to standard immunosuppressive therapy or recurrent graft rejection (per definitions/thresholds in policy); acute or chronic GVHD refractory to medical therapy; and advanced-stage (III/IV) CTCL or progressive, refractory early-stage (I/II) CTCL. Most other solid-organ transplant situations, autoimmune diseases, prophylactic cardiac ECP, and other indications are investigational per the policy.

Thresholds and Evidence Cutoff

Acute rejection timeframewithin first 100 days after transplantation

Recurrent allograft rejectionat least two rejection episodes after standard immunosuppressive therapy

Sézary cell absolute count thresholdat least 1000 cells per cubic millimeter (with immunophenotypical abnormalities or demonstration of a T‑cell clone)

Evidence literature search throughDecember 8, 2025 (added March 23, 2026 review)

Medical Necessity Criteria

Organ rejection after solid organ transplant

Extracorporeal photopheresis may be considered medically necessary when ONE of the following criteria is met:

There is acute rejection that is refractory to standard immunosuppressive drug treatmentacute = within first 100 days after transplantation; refractory = fails to respond adequately to a standard regimen of immunosuppressive therapy

Acute rejection is considered within first 100 days after transplantation; refractory defined as failure to respond adequately to standard immunosuppressive therapy

There is recurrent graft rejectionrecurrent = at least two rejection episodes after standard immunosuppressive therapy

Recurrent allograft rejection is defined as having at least two rejection episodes after standard immunosuppressive therapy

Organ rejection — Not covered/Investigational

Extracorporeal photopheresis is considered investigational for the following:

Coding

Reviewed for Medical Necessity - CPTCPT

36522

Photopheresis, extracorporeal

Claims for CPT code 36522 will be reviewed for medical necessity against the policy criteria and required documentation. Coding and claims will be checked against the policy's medical necessity review process; providers should follow the referenced prior authorization/provider action requirements for records and claims review (see provider actions/prior_auth for claims review instructions).

Provider Actions

Documentation Required

Medical record documentation required

Document in the medical record the diagnosis/condition, history and physical documenting severity, and the medical therapy that has been attempted. These records support review for medical necessity.

Diagnosis/condition
History and physical exam documenting severity
List of medical therapies tried (including agents, doses, duration, and response)

Prior Authorization

Medical necessity review

Claims for extracorporeal photopheresis (ECP) will be reviewed against the policy medical necessity criteria (for example: acute rejection refractory to standard immunosuppressive therapy, recurrent graft rejection, acute or chronic GVHD refractory to medical therapy, and specified CTCL stages such as late-stage III/IV or progressive, refractory early-stage I/II).

Background, Evidence & Guidelines

Background: Extracorporeal photopheresis (ECP) is a leukapheresis‑based immunomodulatory procedure in which leukocyte-rich blood is separated, treated with the photosensitizer 8‑methoxypsoralen, exposed to ultraviolet‑A light, and reinfused. Two photopheresis systems (UVAR XTS and CELLEX) and the photoactive agent UVADEX (8‑methoxypsoralen) have FDA premarket approvals for the palliative treatment of skin manifestations of CTCL unresponsive to other treatments; use for other conditions is off‑label. Evidence sufficiency summary from the policy evidence section: Heart transplant - recurrent/refractory rejection: evidence sufficient; Graft‑versus‑host disease (refractory acute/chronic): evidence sufficient; Advanced‑stage CTCL (III/IV) and refractory early‑stage (I/II): evidence sufficient; Solid organ transplants - general (lung, liver, kidney): insufficient evidence; Autoimmune diseases: insufficient evidence.

Notable CMS / Medicare Determinations

CMS NCD 110.4National Coverage Determination for Extracorporeal Photopheresis (110.4), 2012

CMS coverage — cardiac allograft rejectionEffective 2006: coverage for acute cardiac allograft rejection refractory to standard immunosuppressive therapy

CMS coverage — chronic GVHDEffective 2006: coverage for chronic GVHD refractory to standard immunosuppressive drug treatment

Medicare Determinations

Effective	Name	Number/Type
2006	CMS coverage for cardiac allograft rejection	NCD
2006	CMS coverage for chronic GVHD refractory to standard therapy	NCD
2012	CMS coverage for BOS following lung allograft (research study conditions)	NCD (coverage only when provided under a clinical research study)
1988	CMS coverage for CTCL palliative skin manifestations unresponsive to other therapy	NCD
2012	National Coverage Determination for Extracorporeal Photopheresis	110.4 / NCD

Not Covered / Experimental Indications

Investigational indications (policy investigational criteria): ECP is considered investigational for prophylactic prevention of rejection after cardiac transplantation, and for other situations related to treatment or prevention of rejection in other solid organs (for example, lung, liver, kidney) unless specific medically necessary criteria are met. ECP is investigational for the listed autoimmune diseases (including but not limited to autoimmune bullous disorders, Crohn's disease, diabetes, multiple sclerosis, pemphigus, psoriasis, rheumatoid arthritis, scleroderma, and severe atopic dermatitis), and for all other indications not specifically listed as medically necessary.

Revision History

2026-04-01policy_replacementLatest

Policy 8.01.36 became effective, replacing prior policy 8.01.501.

2026-03-23annual_reviewLatest

Annual review approved March 23, 2026; policy updated with literature review through December 8, 2025; references added; policy statements unchanged.

2025-12-22annual_review