Publication Date:
2010-11-19
Description:
Abstract 675 We have previously identified five biomarker proteins that have diagnostic and prognostic value for acute graft-versus-host disease (GVHD) (Blood 113:273-278, Sci Transl Med 2:50-57). In order to determine whether biomarkers can predict GVHD before the appearance of clinical symptoms, we evaluated the three most informative biomarkers of the five (IL2-Receptor-α, TNFR1, elafin) in patient samples prospectively collected between 2000 and 2010 from 513 unrelated (URD) hematopoietic cell transplant (HCT) patients. We focused on URD HCT recipients because they are most likely to develop acute GVHD and could potentially benefit from a predictive laboratory assay and subsequent preemptive intervention. We measured biomarker plasma levels by sequential enzyme-linked immunosorbent assay on samples obtained prior to conditioning (pre-HCT), and at day +7 and day +14 after HCT. In designing the analytical approach, we took into consideration that median time to GVHD onset is delayed after reduced intensity conditioning, that there may be limited opportunity to preemptively intervene in patients on the verge of developing GVHD, and that there have been changes in GVHD prophylaxis agents over the past decade. Therefore, we randomly divided the patients into training (N=342) and validation (N=171) data sets that were balanced for (i) full intensity conditioning, (ii) onset of grade II-IV GVHD earlier than day +21 and (iii) HCT performed after 2005. In order to create a prediction model for acute GVHD, we used the biomarker levels in the training data set to simulate biomarker values for a hypothetical 50,000 patients using the following assumptions: (1) the incidence of GVHD by day 100 is 55%, (2) the median day of GVHD onset after full intensity URD HCT is day 21, with 10% of patients developing GVHD prior to day +7, and 3% developing GVHD after day +56. These assumptions were based on historical URD HCT data at our center. We used logistic regression to compute a predicted probability, p7, of developing grade II-IV GVHD for each of the 50,000 patients based upon the biomarker levels pre-HCT and at day +7. Any patient with p7≥0.64 was categorized as high risk for development of GVHD. For all low risk patients (p7
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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