Circulating B-cell activating factor level predicts clinical response of chronic graft-versus-host disease to extracorporeal photopheresis

Abstract Extracorporeal photopheresis (ECP) is an important therapeutic option in steroid-refractory chronic graft-versus-host disease (cGVHD). Few biomarkers predicting response exist. We measured serum B-cell activating factor (BAFF) in 46 cGVHD patients receiving ECP before and during treatment course. BAFF level at 1 month of ECP predicted 3- and 6-month skin disease response, with BAFF less than 4 ng/mL associated with significant skin improvement and complete resolution in 11 of 20 patients. High BAFF at 1-month ECP associated with a worsening median 6-month skin score and resolution in 1 of 10 patients. BAFF level at 3 months also predicted the likelihood of maintaining skin disease improvement at 6 months. BAFF level was not correlated directly with extracutaneous cGVHD response, although full cutaneous responders exhibited improved extracutaneous organ response rates compared with skin nonresponders (65% vs 35%). This study suggests that early BAFF measurement during ECP for cGVHD represents a potentially useful biomarker in prediction of treatment outcome.

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High Levels of B-Cell Activating Factor During the Peri-Transplant Period Are Associated with the Reduced Incidence of Acute Graft-Versus-Host Disease Following the Myeloablative Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.2229.2229 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2229-2229

Author(s):

Byung Sik Cho ◽

Chang Ki Min ◽

Hee Je Kim ◽

Seok Lee ◽

Yoo Jin Kim ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

B Cell ◽

Graft Versus Host Disease ◽

Allogeneic Stem Cell Transplantation ◽

Cutoff Value ◽

Graft Versus Host ◽

B Cell Activating Factor ◽

Time Point ◽

Baff Level

Abstract Abstract 2229 Poster Board II-206 To determine whether serum B-cell activating factor (BAFF) levels that were previously found to be elevated in patients with chronic graft-versus-host disease (GVHD), and C-reactive protein (CRP) levels known as a predictor for aGVHD as well as a marker for systemic inflammation during the peri-allogeneic stem cell transplantation (SCT) period, could be used to predict the occurrence of acute GVHD (aGVHD), 45 consecutive patients who had undergone myeloablative allogeneic SCT for hematologic malignancies were assessed. Serum BAFF and CRP levels were measured using ELISA (R&D Systems, Minneapolis, MN, USA) before conditioning and on day 0, day +7, and day +14 after transplant. Thirty-three of 45 patients (cumulative incidence, 73=) developed aGVHD between 16 days and 98 days after transplant. Analyses using repeated measures of ANOVA revealed that the serum BAFF levels were significantly lower in patients with aGVHD than in those without aGVHD (P=0.001), whereas no association was detected between CRP levels and aGVHD (P=0.508). Receiver operating characteristic curve (ROC) analysis showed that serum BAFF levels at every time point were available for the prediction of development of aGVHD (pre-conditioning; P=0.005, day 0; P=0.002, day +7; P=0.004, and day +14; P=0.005). Using ROC curve analysis, the identical cutoff value of 43 pg/ml at every time point that divides patients into two groups, high (> 43 pg/ml) or low (≤ 43 pg/ml) BAFF group, was determined, which could assure 75= sensitivity and 73-82= specificity for the prediction of aGVHD at every time point. The analyses of the cumulative incidence of aGVHD at each time point by BAFF groups (high vs. low) showed that serum BAFF level at every time point plays a significant predictive role for the occurrence of aGVHD (pre-conditioning; P=0.040, day 0; P=0.023, day +7; P=0.003, and day +14; P=0.026). This study is, to the best of our knowledge, the first to show that high serum BAFF levels during the peri-transplant period may play a protective role against aGVHD in humans. The results of this study also show that the BAFF levels during peri-transplant period may be considered to be a predictor for aGVHD. Further trials with a larger cohort will be necessary to determine a definite cutoff value of high BAFF level as well as to construct an index with previously known factors for the prediction of aGVHD. Disclosures: No relevant conflicts of interest to declare.

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