Using Lymphocyte Phenotypes to Predict Successful Responses to Extracorporal Photopheresis (ECP) in Patients Suffering from Chronic GvHD

CGVHD develops in more than 50% of survivors of allogeneic stem cell transplantation and is responsible for mortality in one third of patients.  Long-term immunosuppressive therapy with steroids is the standard treatment.  ECP is successful in about 50% of the patients after 3 – 6 months of therapy.  To define markers that might predict successful ECP therapy, we performed an immunological assessment of 22 patients with cGVHD prior to initiating ECP.  In addition, a comprehensive assessment of organ system involvement using NIH Consensus response assessment tools was done at study entry and at six months.  Eighteen patients completed the study with improvement of GvHD symptoms observed in eleven patients; seven patients failed to respond to therapy.  PBMCs from leukopheresed blood were obtained prior to the onset of ECP therapy.  Patients who responded to ECP therapy consistently had a lower CD4/CD8 ratio than non-responders (0.80 ± 0.64 vs. 3.7 ± 3.1, p < 0.01).  The percentages of CD4⁺ and CD8⁺ T cells that expressed CD25, CD45RA, or FoxP3 were not different between the two groups.  Within the B cell populations, the phenotype of CD21^-CD24⁺ cells varied between responders and non-responders with fewer cells expressing IgD in the responders than in the non-responders; 61% ± 19% of CD21^-CD24⁺ B cells were IgD⁺CD27^- in patient who responded to ECP, as compared to 80% ± 10% in patients who did not respond to ECP, p < 0.05.  The identity of these cells is not known, but they may represent a memory B cell compartment.  In addition to obtaining PBMCs prior to ECP, cells were also obtained at 2, 4, and 6 months after the onset of ECP to define parameters that might track the recovery of GvHD.  The percentage of CD3^-CD20^- cells that were CD34⁺ cells increased in patients responding to ECP, but decreased in patients not responding to ECP.  The results of our pilot study suggested that the lymphocyte phenotype might be a useful predictive marker for successful ECP therapy.  In addition, changes in the CD34⁺ population might provide an objective marker for ECP responsiveness.