Prevention of Transfusion-Associated Graft Versus Host Disease (TA-GVHD) by Photochemical Treatment of Platelet Components: Clinical Experience in Routine Use.
Authors: Osselaer Jean Claude , Doyen Chantal , Graux Carlos , Chatelain Christian , Sonnet Anne , Jacquet Michele , Lin Jin Sying , Corash Laurence , Bosly Andre 
Published: October 2019

Background: In 2003 the Blood Transfusion Center, Cliniques Universitaires Mont Godinne, Yvoir, Belgium implemented routine use of pathogen inactivation photochemical treatment (PCT) of platelet (PLT) components (INTERCEPT™ Blood System, Cerus Europe, Leusden, The Netherlands) for transfusion support of thrombocytopenia. Based on in vitro clonal T cell proliferation assays (> 5 log T cell inactivation), biochemical assays (1 adduct every 83 base pairs), animal studies (prevention of GVHD in a parent to F-1 model), and clinical trial experience (Bone Marrow Transplantation2004; 33: 1–7), PCT of PLT was used in place of gamma irradiation to inactivate residual donor T cells for prevention of TA-GVHD. Other blood components continued to be treated with gamma irradiation according to standard operating procedures. Surveillance of all patients at risk for TA-GVHD transfused with PCT PLT was conducted for 3 years (11/2003 – 11/2006) after adoption of PCT, and the incidence of TA-GVHD determined.

Methods: PLT were collected on the Amicus Cell Separator (Fenwal Blood Technologies, Nivelles, Belgium) with process leuko-reduction. PLT were suspended in Intersol (Fenwal) with a ratio to plasma of ∼ 65:35%. PLT containing 2.5 to 6.0 × 1011 plts in ∼ 300 mL were prepared with an integrated processing set using amotosalen (150 uM) and UVA (3 J/cm2) to inactivate pathogens and leukocytes. PCT PLT units were issued the day after collection and stored for up to 7 d. Hematopoietic stem cell transplant (HSCT) patients were selected as a high risk population for TA-GVHD, and monitored for evidence of TA-GVHD with an active hemovigilance program. TA-GVHD was diagnosed using established criteria (N Engl J Med1990; 323:315–21).

Results: During 3 years, 756 patients received 7,538 PCT PLT transfusions and 76 patients with a spectrum of hematologic diseases (Table) were treated with HSCT (n = 93: 75 auto- and 18 allo-grafts) and were supported with PCT PLT. 15 patients received 2 auto grafts, and one received 3. All HSCT patients were deemed at risk for TA-GVHD due to immune suppressive and/or myelo-ablative therapy including TBI (n = 19). Auto graft patients (n = 59) received a median of 7 PCT PLT (range 2–94). Allo graft patients (n = 17) received a median of 11 PCT PLT (range 3 – 127). No patient developed evidence of TA-GVHD during the 3-year period.

Conclusions: PCT of PLT prevented TA-GVHD in a population of HSCT patients at risk for TA-GVHD exposed to multiple platelet transfusions. Use of PCT to treat all PLT components avoided the need to identify at risk patients and permitted the use of a single PLT inventory. These clinical data support the use of PCT for replacement of gamma irradiation to prevent TA-GVHD.

Diagnoses of HSCT Patients At Risk For TA-GVHD Diagnosis/Year 2003 2004 2005 2006 Total % Myeloma 2 7 9 7 25 32.9 NH Lymphoma 2 6 8 7 23 30.2 Acute Leukemia 2 2 4 4 12 15.8 Hodgkins 0 3 1 0 4 5.3 Myelofibrosis 0 3 0 1 4 5.3 Myelodysplasia 0 1 0 1 2 5.3 Solid Tumor 0 1 1 0 2 2.6 CLL 0 1 1 0 2 2.6 CML 0 1 0 0 1 1.3 Waldenstrom’s 0 1 0 0 1 1.3