Prevention of GVHD in Patients Treated With Allogeneic SCT: Possible Role of Extracorporeal Photophoresis

Allogeneic stem cell transplantation represents the only available long-term control and possible cure of a number of hematological malignancies. A major obstacle to this treatment is the development of graft-versus-host disease (GVHD), affecting the majority of transplanted patients to some extent. Today, combinations of various cytotoxic and immunosuppressive drugs are used to prevent and treat GVHD, but many of them are associated with severe side-effects. Extracorporeal photophoresis (ECP) offers an alternative to chemo- and immunosuppressive therapy and confers apparently only mild side effects. The postulated rationale of ECP is to treat the patient's white blood cells ex vivo with ultraviolet irradiation after sensitization with 8-methoxypsoralen to dampen their immunoactivity. After engraftment the intervention group receives 2 consecutive ECP every week in 2 weeks then 1 ECP every week in 4 weeks ( a total of 8 ECP procedures).

• Extracorporeal photophoresis (ECP) (Other): The treatment procedure of ECP consists of three steps. First, the leukocytes are removed by apheresis; second, the mononuclear cells are primed with the photosensitizing agent 8-methoxypsoralen; then third, these cells are exposed to radiation with ultraviolet A light before they are re-infused into the patient

Primary outcomes

• Reduce the frequency of GVHD by preventive treatment with ECP of patients undergoing allogeneic stem cell transplantation for hematological malignancies [up to 1 year after allogeneic stamcell transplantation]: GVHD is measured according to internationally recognized criteria

Secondary outcomes

• Number of survivors the first year after transplantation [Through study completion, and until 1 year after study start]: In the follow-up periode mortality rate in both groups is registered
• Number of patients who relapsed the first year after transplantation Number of patients who relapsed the first year after transplantation Number of patients who relapsed the first year after transplantation [Through study completion, and until 1 year after study start]: In the follow-up periode relapse rate in both groups is registered
• Quality of life (QoL) the first year after transplantation [Through study completion, and until 1 year after study start]: In the follow-up periode EORTC-QLQ-C30 scores in both groups are registered
• Assessment of vitamin A derivatives [From randomization to 3 months after transplantation]: Measurement of retinoids and carotenoids in plasma before and after ECP treatment
• Determination of microbiota [Through study completion, and until 1 year after study start]: Assaying fecal microbiota from both study groups.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Provide written consent to participate
* Understand Norwegian or English
* No previous history of malignant disease
* No contraindication to ECP-treatment or undergone previous ECP treatment

Exclusion Criteria:

* (in addition to those regarding eligibility for transplantation itself):

  * Unwilling to provide written consent to participate
  * Unable to cooperate as judged by the responsible physician
  * ECOG status > 2 at time of inclusion
  * Using anti-inflammatory or cytotoxic drugs other than those that are part of the treatment of the current hematological malignancy
  * Known allergy to psoralens or citrate products
  * Splenectomy
  * Pregnancy/lactating

• Results publication: Iversen PO, Ali MM, Bastani NE, Blomhoff R, Tjonnfjord GE, Gedde-Dahl T. Plasma Levels of Retinoids and Carotenoids in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation Given Extracorporeal Photopheresis to Prevent Graft-Versus-Host Disease-Analyses From a Randomized Trial. EJHaem. 2026 May 13;7(3):e70296. doi: 10.1002/jha2.70296. eCollection 2026 Jun. PMID 42137823

• Geir E Tjønnfjord, Prof,MD,PhD, Study chair, Oslo University Hospital HF, Department of Haematology Rikshospitalet
• Per Ole Iversen, Prof,MD,PhD, Study chair, Oslo University Hospital HF, Department of Haematology Rikshospitalet