Updateonextracorporealphotochemotherapyforgraft-versus-hostdisease treatment J Kanold 1 , C Messina 2 , P Halle 1 , F Locatelli 3 , E Lanino 4 , S Cesaro 2 and F Deme´ocq 1 , on behalf of the Paediatric Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT) 1 Unite´Bioclinique de The´rapie Cellulaire, C.H.U. Clermont-Ferrand, France; 2 Pediatric hematology and oncologic Unity, University of Padua, Italy; and 3 IRCCS Policlinico S Matteo, Pavia, Italy; 4 IRCCSG, Gaslini, Genova, Italy Summary: Pediatric experience with extracorporeal photochemo- therapy (ECP) for graft-versus-host disease (GvHD) has mainly been reported by Italian and French groups. Data concerning 41 children with acute GvHD and 63 children affected by chronic GvHD are available. In 73 and 63% of them, respectively, improvement was observed, with addition of ECP to their immunosuppres- sive regimen. Treatment with ECP was associated with minimalsideeffects,eveninthesmallestofpatients.Inall responded pediatric patients, both with acute and chronic GvHD, ECP allowed progressive reduction or disconti- nuation of the concomitant pharmacological immunosup- pressive therapy without an increase in GvHD acitivity. ThesedatashowthatECPisausefultherapyforchildren affectedbyGvHDresistanttoconventionaltreatmentand can be safely used. Bone Marrow Transplantation (2005) 35, S69–S71. doi:10.1038/sj.bmt.1704851 Keywords: extracorporeal photochemotherapy; children; graft-versus-host disease Extracorporeal photochemotherapy (ECP), based on the immunomodulating action of UV-A irradiation on blood mononuclear cells collected by apheresis and photosensi- tized by 8-methoxypsoralen (8-MOP), is an alternative therapeutic modality for graft-versus-host disease (GvHD) treatment. Although its exact mechanism of action is not fully understood (several cellular/cytokine changes were demonstrated) and results of randomized studies are not yet available, worldwide experience with ECP for GvHD has grown enormously over the past decade. Pediatric experience with ECP for GvHD (to date, results on about 100 children treated are available) has mainly been reported by Italian 1–9 and French 10–15 groups. Most of this has been in the form of case reports or small series. The largest cohorts are two retrospective studies: one multi- center Italian (77 patients) 9 and one French monocenter experience (20 patients). 15 With this overview, we would like to shine some light on ECP in the treatment of GvHD in children, a subject that is perhaps little or poorly understood but which definitely merits attention. For the indication and eligibility for ECP treatment there are some consensual criteria (GvHD not responding to ‘conventional treatment’, no concomitant treatment with ALG/ATG or monoclonal antibodies causing lymphocytes lysis, complete hematological remission), and some ques- tions, such as the number of circulating lymphocytes, and whether there was stable engraftment. For acute GvHD, the situation is relatively clear as there exists a definition for the nonresponse after 1 week of steroid therapy. For chronic GvHD, the variability in the definition of non- responding disease is an important factor of confusion that affects evaluation. Also, the timing-schedule of ECP treatment in GvHD is still under discussion. Once again, a certain degree of consensus exists: (1) treatment schedules for acute GvHD with a single-day treatment three times a week or 2 consecutive days once a week, at the beginning, (2) progressive tapering for both acute and chronic disease. Over the last few years, treatment intensification has been explored in patients recently enrolled when compared to earlier patients. Moreover, a better outcome seems to be associated with ECP given early after the onset of disease. However, many questions about treatment duration and total number of sessions remain. Two techniques are currently used with considerably more patients treated by Cobe Spectra and Uvamatic than by Therakos (69 vs 33 patients reported). This could be explained by minimization of the extracorporeal volume and shortening of the time of a sedentary period of procedure (collection), which are of importance in the pediatric context. The main difficulties in ECP role’s assessment in published clinical trials are: (1) marked heterogeneity of patients enrolled, specially for chronic disease, because of no agreed definition of ‘nonresponding GvHD’; (2) a large variability in timing between the onset of disease and the start of ECP; (3) different treatment protocols and Correspondence: Dr J Kanold, Unite´ Bioclinique de The´rapie Cellulaire, Service d’He´matologie et d’Oncologie Pe´diatrique, Hoˆtel Dieu, C.H.U., B.P.69, 11, Boulevard Le´on Malfreyt, 63000 Clermont-Ferrand, France; E-mail: jkanold@chu-clermontferrand.fr Bone Marrow Transplantation (2005) 35, S69–S71 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00 www.nature.com/bmt