Detecting The Biomarkers Of Acute Gaft-versus-host Disease And Investigating The Role Of Its Pridicting The Risk And Prognosis For Patients After Myeloablative Unrelated Cord Blood Transplantation

Object: Acute graft-versus-host disease is major complications and causes of death after allogeneic hematopoietic stem cell transplantation. However there is no reliable way to predict its occurrence and influence on prognosis. In this study, we monitor the biomarkers of ST2, elafin, and REG-3α in patients’ peripheral blood, then analysis the clinical occurrence of a GVHD.Method: In this research, we choose the patients with hematologic malignancies who received umbilical cord blood transplantation(UCBT) in department of hematology of anhui provincial hospital from July 2013 to July 2014 as participants. Using myeloablative conditioning regimen.Collect 5 ml peripheral blood from patients who received UCBT at day 5, day 14, and day 30. Samples were centrifugal for 8 min under 1500 RPM, then stored in the refrigerator of-80℃. ELISAs method was used through test the ST2, elafin, and REG-3α in patients’ peripheral blood to study the incidence of GVHD after transplantation. To compare the occurrence of GVHD at different timepoints after UCBT, and divide the patients into two groups. Compare the two groups of patients with the concentration of biomarkers.Result: 1. A total of 43 patients were undergoing UCBT, 43 patients achieved engraftment. The median time for neutrophil get engraftment was 18 days. The median time for platelet get engraftment was 46 days after UCBT. Of these 43 patients, 23 patients developed a GVHD between 15 days and 96 days after transplantation(53.5%). Of the total 23 patients with a GVHD, 14 patients had grade Ⅰ- Ⅱa GVHD and 9 patients had Ⅲ-Ⅳa GVHD. The median time was 27 days after UCBT. Among the total 23 patients, 14 patients(61%) had a complete response to corticosteroid treatment, and the 9 steroid-refractory patients(39%) received second-line therapy. The cumulative incidences of the post-transplantation septicemia, hemorrhagic cystitis, TMA, and CMV infection during the follow-up period were 30.2%, 34.9%, 4.7%, and 65.1%, respectively.2. ST2 level was measured on day 5, day 14 and day 30. The increased ST2 levels at day 14(a GVHD 280pg/ml,no a GVHD 90pg/ml) and day 30(a GVHD 340pg/ml,no a GVHD 130pg/ml) were observed in patients who developed a GVHD post-transplantation(P=0.022, and P=0.007). However, no significant association was found between a GVHD and ST2 level at day 5(a GVHD 128pg/ml,no a GVHD 203pg/ml)(P=0.38). According to the classification of a GVHD, we divided the patients into three groups; grade I-II group, grade III-IV a GVHD group, and no a GVHD group. From this study, we can conclude that the level of ST2 in grade III-IV a GVHD group in day 14 and day 30 after UCBT were 600pg/ml and 500pg/ml, respectively, which were higher than the other two groups. However, the ST2 value in grade III-IV a GVHD group was significantly higher than grade I-II group at day 14(P=0.001), there was no relationship between the second group and the third group whether at day 14 or day 30(P=0.301, P=0.092, respectively). Patients with a high and a low ST2 value at day 14 after UCBT, 6-month mortality without relapse was 32.6% and 4.4%, respectively(P=0.003).3. Among a total of 21 cord blood recipients, an amount of 14 patients have developed skin a GVHD. Elafin level was measured on day 5, day 14 and day 30. The study concluded that increased elafin levels at day 14 was observed in patients who developed skin a GVHD post-transplantation(P=0.028). However, no significant association was found between a GVHD and elafin level at day 5 and day 30(P=0.185 and P=0.732).4. A total of 11 patients developed LGI GVHD. REG-3α level was measured on day 5, day 14 and day 30. The study demonstrated that the level of REG-3α at each timepoint were 0.4ng/ml and 0.9ng/ml,1.65 ng/ml and 1.2ng/ml,0.9 ng/ml and 0.8ng/ml between a GVHD and no a GVHD patients. No significant association was found between REG-3α level and patients who developed LGI GVHD at each time point.(P=0.698, P=0.067, and P=0.502, respectively). However, we can observe a trend that REG-3α value was obviously higher in LGI GVHD patients compared with no LGI GVHD patients on day 14. The REG-3α value had no relevant to the grade of LGI GVHD.Conclution: 1. Our results suggest that ST2 and elafin can be a potential plasma biomarker of a GVHD after myeloablative unrelated cord blood transplantation. An trend can be observed that REG-3α value was obviously higher in LGI GVHD patients compared with no LGI GVHD patients on day 14, but it need to expand the number of cases for further conforming.2. Plasma ST2 values at day 14 after UCBT were associated with 6-month mortality without relapse.