BB02 Improves Therapeutical Effectiveness Of Extracorporeal Photopheresis With 8-MOP In a Murine Model Of Graft-Versus-Host Disease

  1. Garcia-Bernal, David 1
  2. Blanquer, Miguel 1
  3. del Rio, Jose Antonio 2
  4. Correal, Enrique 3
  5. del Carmen Algueró, Maria 1
  6. Majado, Maria Juliana 5
  7. Moraleda, Jose María 4
  1. 1 Cellular Therapy and Hematopoietic Transplant Unit, Hematology Department, University Hospital Virgen de la Arrixaca. University of Murcia, El Palmar-Murcia, Spain,
  2. 2 Vegetal Physiology, University of Murcia, Espinardo-Murcia, Spain,
  3. 3 Department of Natural Resources, Instituto Murciano de Investigacion y Desarrollo Agrario y Alimentario (IMIDA), La Alberca-Murcia, Spain,
  4. 4 Cellular Therapy and Hematopoietic Transplant Unit, Hematology Department, University Hospital Virgen de la Arrixaca, University of Murcia, El Palmar-Murcia, Spain
  5. 5 Cellular Therapy and Hematopoitic Transplant Unit, Hematology Department, University Hospital Virgen de la Arrixaca. University of Murcia, El Palmar-Murcia, Spain,
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Revista:
Blood

ISSN: 0006-4971,  1528-0020

Año de publicación: 2013

Volumen: 122

Número: 21

Páginas: 5416-5416

Tipo: Artículo

DOI: 10.1182/BLOOD.V122.21.5416.5416 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Blood

Resumen

IntroductionExtracorporeal photopheresis (ECP) is a cell-based immunomodulatory therapy involving the separation of peripheral blood autologous mononuclear cells followed by ex-vivo administration of 8-methoxypsoralen (8-MOP) and UVA radiation before reinfusion. ECP is efficient for the treatment of multiple diseases mediated by unregulated T cell populations, such as cutaneous T cell lymphoma, autoinmune diseases or graft-versus-host disease (GVHD), the major complication after allogeneic bone marrow transplantation. Our aim in the present work was to compare the therapeutic effectiveness of 8-MOP with other two new compounds (BB01 and BB02) in a experimental murine model of GVHD.MethodsMurine GVHD was induced after transplanting bone marrow cells and splenocytes from donor Balb/c mice into C57Bl6J recipients previously conditioned with a lethal dose of 10 Gy split into two doses of 5 Gy spaced 24 hours apart. To investigate the therapeutic effectiveness of ECP with either 8-MOP, BB01 or BB02, splenocytes from separate cohorts of C57Bl6J with GVHD were isolated 12 days after transplantation, incubated with the different compounds, irradiated with UVA light and injected intravenously once a week for four weeks. Survival after transplantation was monitored daily and clinical GVHD was graded using a previously described score analyzing weight loss, posture (hunching), activity, skin integrity and fur texture (Cooke et al, 1996). Mice of each group were evaluated and graded from 0 to 2 for each criterion, obtaining a clinical index by summation of the five criteria scores (maximum index=10).ResultsMice treated weekly with BB02 showed a significant higher survival than those treated with 8-MOP (p=0,038), while BB01 had a similar effect to that of 8-MOP. Mice treated with either compound improved their clinical GVHD score compared to untreated mice group, being significantly lower with BB02 than with BB01 and 8-MOP (p=0,023).ConclusionsBB02 was more efficient than 8-MOP in the reversal of murine GVHD, while BB01 showed the same therapeutic effectiveness than 8-MOP.