Receiver operating characteristic curve analysis of circulating blood dendritic cell precursors and T cells predicts response to extracorporeal photopheresis in patients with chronic graft‐versus‐host disease

Abstract

BACKGROUND One proposed mechanism of extracorporeal photopheresis (ECP) in reducing chronic graft-versus-host disease (cGVHD) is alteration in numbers of circulating dendritic cells (DCs). This hypothesis was tested by correlating numbers of DC precursors and T cells in the blood before and during ECP therapy with response of cGVHD. STUDY DESIGN AND METHODS Twenty-five patients with cGVHD were treated with ECP. Data were collected with emphasis on blood cellular markers, clinical response to ECP, and overall survival. RESULTS Fourteen patients (56%) responded and had better 2-year survival than nonresponders (88% vs. 18%, p = 0.003). Responders had higher baseline circulating myeloid DC (mDC) and plasmacytoid DC precursors and CD4+ and CD8+ T cells compared with nonresponders. Receiver operating characteristic curve analyses showed that the best baseline cutoff values to predict response to ECP were mDC counts of 3.7 cells/µL (79% sensitivity, 82% specificity) and CD4+ T-cell counts of 104 cells/µL (71% sensitivity, 82% specificity). CD4+ T cells declined in responders over time, but not in nonresponders, and no significant changes were seen in CD8 T-cell or DC numbers over a 12-month period in responder or nonresponder groups. CONCLUSIONS Higher baseline numbers of circulating DCs and T cells may predict clinical response to ECP in patients with cGVHD.

Response of steroid‐refractory chronic graft‐versus‐host disease to extracorporeal photopheresis correlates with the dose of CD3+ lymphocytes harvested during early treatment cycles

“…Conversely, Akpek GVHD prognostic score seems to have no influence. 17,19 Finally, the observation that earlier ECP initiation may lead to better results 20 was not confirmed by subsequent studies, 19,21,22 and there is no clear evidence about the superiority of an ECP schedule among others. A retrospective study on a large cohort of cGVHD patients found ECP response to be associated with nonmyeloablative transplant, use of donor lymphocyte infusions, and lung involvement.…”

“…A 2002 study demonstrated that the presence of expanded clonal T‐cell populations in the peripheral blood of patients before treatment is significantly associated to probability of response . Another group reported that ECP responders have an higher absolute number of CD4+ and CD8+ cells, compared to nonresponders, 3 and 6 months after the onset of ECP, while more recently, the probability of response to ECP was found to be related with the baseline number of circulating myeloid and plasmocytoid dendritic cell precursors and CD4+ and CD8+ lymphocytes . Other studies focused on the B‐cell lineage: authors have shown that there is an association between immature B cells (i.e., CD19+, CD21–) in peripheral blood and response to ECP …”

Discovery and validation of graft-versus-host disease biomarkers

“…12 Dendritic cells, monocytes, and ␥-␦ T cells are also promising as markers after HSCT. 13,14 In cGVHD, B cells and their modulators (eg, B cell-activating factor) are important biomarkers. 15 …”

Current Clinical Applications of Extracorporeal Photochemotherapy

“…Akhtari et al. showed that patients suffering from chronic GvHD with a high starting number of DCs, CD4+, and CD8+ T cells circulating in the peripheral blood responded better to ECP treatment compared with non‐responders. Consequently, before initiating ECP, the determination of DCs and T cells can be considered as a predictor factor of clinical response to ECP in patients with chronic GvHD.…”