Transfusion medicine

Therapeutic apheresis


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PubMed Search: Extracorporeal photopheresis [title] "loattrfree full text"[sb]

Garrett S. Booth, M.D., M.S.
Huy P. Pham, M.D., M.P.H.
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Cite this page: Pham HP, Booth G Photopheresis. website. Accessed May 30th, 2023.
Photopheresis and extracorporeal photopheresis
  • Process of removing mononuclear cells (MNC - monocytes and lymphocytes) from the patient and treating these MNCs with 8-methoxypsoralen (8-MOP) and ultraviolet light (UVA, 320 - 400 nm wavelength)
    • Following UVA photoactivation, the MNCs are returned to the patient
    • This process can be performed on a discontinuous device (UVAR XTS) or a continuous apheresis device (CELLEX)
    • This process of MNC collection, treatment and photoactivation takes place outside of the patient (ex vivo), thus, the process can also be called extracorporeal photopheresis (ECP)
  • Initially approved by the FDA to treat cutaneous T cell lymphoma (CTCL), the only FDA approved indication in the U.S. to date
  • Also used to treat graft versus host disease / GVDH (Nat Clin Pract Oncol 2006;3:302), heart and lung transplant rejection

  • Therakos UVAR XTS:
    • Operates on discontinuous cycle
    • Single needle access
    • Uses either 125 mL (small bowl) or 225 mL Latham bowl to collect MNCs (3 - 6 cycles)
      • Small bowl is used for pediatric patients, patients with anemia (HCT < 36%), lower body weight (< 45 kg) or hemodynamic instability
    • Extracorporeal volume (ECV) ranges from 220 to 620 mL
    • Typically takes ~4 hours to finish

  • Therakos CELLEX:
    • Operates on continuous cycle
    • Single or double venous access
    • ECV is 266 mL for single needle and 216 mL for double needle procedures
    • Can be used for patients who weigh as little as 22 kg
    • Typically takes ~1.5 hours to finish
    • Reference: Br J Dermatol 2009;161:167

  • 8-methoxypsoralen (8-MOP):
    • Psoralen based medication used in ECP
    • Functions by binding to the DNA backbone when photoactivated with UVA, thus preventing future cell division / replication
ECP principles
  • The exact mechanism of action for ECP is unclear
  • Overall, this procedure helps to change the regulatory balance of the immune system
  • Multiple theories exist as to how this is undertaken, including:
    1. A decrease in T cell proliferation
    2. Human leukocyte antigen (HLA) modulation of cytotoxic CD8+ cells
    3. Increasing donor regulatory T cells (CD4+, CD25+)
    4. Decreasing the numbers of circulating dendritic cells
Vascular access
  • Therakos UVAR XTS machine operates using a discontinuous flow; thus, it only requires a single needle venous access (J Clin Apher 2017;32:462)
  • Therakos CELLEX machine operates using a continuous flow; thus, either single or double venous access can be used (J Clin Apher 2017;32:462)
  • ECP can be performed either with peripheral IV access or with a central venous catheter (CVC)
  • For patients undergoing chronic ECP, often a CVC is used to ensure adequate venous access
  • Emergent procedures are not performed as numerous ECP procedures are often needed before there is evidence of clinical benefit
  • The American Society for Apheresis (ASFA) delineates ECP exchange indications by the acuity of the clinical situation (J Clin Apher 2013;28:145)
  • ECP indication for CTCL (MF / SS):
  • ECP indication for cardiac transplantation:
  • ECP indication for lung transplantation: bronchiolitis obliterans syndrome category II (J Clin Apher 2011;26:146)
  • ECP indication for acute and chronic GVHD:
Adverse events
  • ECP is a safe and well tolerated procedure
  • ECP does not require exposure to blood / blood products
  • Patients may require blood transfusion prior to ECP to maintain a safe extracorporeal blood volume

  • Minor adverse events:
    • Low grade fevers may occur within 2 - 12 hours post infusion of MNCs
    • A temporary increase in pruritis or erythema may be seen in patients with CTCL
    • Psoralen medications can remain in the peripheral circulation following ECP therapy; patients may be photosensitive and should avoid UV exposure
    • Recommended to avoid a high fat meal at least 7 hours prior to ECP, as plasma opacity from triglycerides could interfere with the separation as well as the photoactivation process
    • Similar difficulty in the interface detection can occur in patients with high bilirubin levels

  • Contraindications:
    • Psoralen compounds are contraindicated in patients with aphakia or with a photosensitive disease (e.g. porphyria cutanea tarda)
    • Patients with psoralen allergies should avoid ECP; additionally, patients allergic to common sources of psoralens like figs or celery should be evaluated by an allergist prior to initiation of therapy
    • Heparin is used as an anticoagulant in ECP; thus, it is contraindicated in patients with a history of heparin induced thrombocytopenia (HIT)
Clinical features
  • ASFA guidelines can be broken down by acute indications and nonacute / chronic ASFA recommendations
  • The diagnosis of CTCL is based on history, physical, flow cytometry and biopsy assessment
  • The diagnosis of cardiac rejection can be made by biopsy assessment as well as clinical status changes
  • The diagnosis of lung transplant rejection can be made by biopsy as well as followed by pulmonary lung function testing (PFT)
  • Graft versus host disease can be assessed clinically (skin involvement, GI involvement - diarrhea, lung - PFT) and by biopsy
  • Prior to initiating ECP, both the patient and laboratory values should be assessed
  • Try to limit the amount of blood outside of a patient to < 15%
  • For patients with low HCT, preprocedure transfusion may be required
  • Additionally, there can be small platelet losses from ECP, therefore a patient must be assessed for bleeding risk prior to ECP initiation
  • Combination therapy for solid organ and stem cell transplant graft versus host disease is often required
  • The use of ECP can help to reduce the overall steroid dose that many treatment refractory patients experience
  • For CTCL:
    • MF: One cycle (2 consecutive days) for every 2 - 4 weeks for at least 6 months
    • SS: One cycle for every 2 weeks for at least 6 months
    • Maintenance therapy: one cycle every 6 - 12 weeks with the goal of discontinuation if no relapses occur
    • If CTCL recurs, then the plan is one cycle for every 2 - 4 weeks
  • For cardiac allograft rejection:
    • No consensus on the treatment protocol
    • An example of a treatment plan reported in the literature is 1 cycle weekly initially, then every 2 - 8 weeks for several months
    • No definite data exists regarding duration, interval or tapering protocol for ECP
  • For lung allograft rejection:
    • No definite data exists regarding duration, interval or tapering protocol for ECP
    • Largest case series:
      • 24 procedures over 6 months
        • One cycle is 2 treatments on consecutive days
        • Five cycles over the first month = 10 treatments
        • One cycle biweekly × 2 months = 4 cycles = 8 treatments
        • One cycle monthly × 3 = 3 cycles = 6 treatments
  • For GVHD:
    • No definite data exists regarding duration, interval or tapering protocol for using ECP to treat acute or chronic GVHD
    • Acute GVHD:
      • No consensus on the treatment protocol
      • An example of a treatment plan reported in the literature is 1 cycle weekly until disease response (~4 weeks) and then tapering to biweekly before discontinuing
    • Chronic GVHD:
      • No consensus on the treatment protocol
      • An example of a treatment plan reported in the literature is one cycle weekly until response or for 8 - 12 weeks, following by tapering to every 2 - 4 weeks until maximal response
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