Epidermal growth factor (EGF) is a recently described biomarker of acute GvHD (aGvHD). Whether low plasma EGF prior to hematopoietic cell transplantation (HCT) predisposes to the development of aGvHD, or whether EGF levels fall because of severe aGvHD, is unknown. To evaluate this, we tested plasma samples collected at pre-HCT baseline, day +28 and day +100 during the course of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. We found that baseline EGF plasma concentrations were three-fold lower in HCT recipients compared to donors (24.3 vs 76.0 pg/mL, P<0.01). Ninety-one patients (43%) had a markedly low plasma EGF at pre-HCT baseline, defined as <2.7 pg/mL-an optimal cutpoint associated with development of grade III-IV aGvHD. Patients with these low EGF levels at pre-HCT baseline had a 2.9-fold increased risk of grade III-IV aGvHD by day +100. Patients with low EGF at day +28 after HCT had an increased risk of death (relative risk 2.3, P=0.02) by 1 year due to transplant-related toxicities, especially aGvHD. Our results suggest that very low plasma EGF early in the HCT process may predispose patients to an increased risk of death, potentially due to epithelial damage and limited repair capacity.
Bibliographical noteFunding Information:
We gratefully acknowledge the BMT CTN 0402 study investigators and participating centers. Support for this study was provided by grant No. U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung and Blood Institute and the National Cancer Institute at the National Institutes of Health, along with contributions from Wyeth Pharmaceuticals Inc. This ancillary study of plasma samples was supported by grants from the National Marrow Donor Program (SGH and LFN) and the Masonic Cancer Center (SGH). This work was also supported in part by NIH P30 CA77598, utilizing the Masonic Cancer Center, University of Minnesota shared resource of Oncology Medical Informatics & Services. We thank Michael Ehrhardt of the UMN Cytokine Reference Laboratory for expert technical assistance. The content is solely the responsibility of the authors and does not necessarily represent the official views of the above-mentioned parties.
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