Assessment of ST2 for Risk of Death Following Graft-versus-Host Disease in the Pediatric and Adult Age Groups

2019 ◽  
Author(s):  
Courtney Rowan ◽  
Francis Pike ◽  
Kenneth R. Cooke ◽  
Robert Krance ◽  
Paul A. Carpenter ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Age Groups ◽  
Host Disease ◽  
Adult Age ◽  
Graft Versus Host ◽  
Risk Of Death

scholarly journals Assessment of ST2 for risk of death following graft-versus-host disease in pediatric and adult age groups

Blood ◽  
2020 ◽  
Vol 135 (17) ◽  
pp. 1428-1437 ◽  
Author(s):  
Courtney M. Rowan ◽  
Francis Pike ◽  
Kenneth R. Cooke ◽  
Robert Krance ◽  
Paul A. Carpenter ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Age Groups ◽  
Tumor Necrosis Factor Receptor ◽  
Risk Groups ◽  
Host Disease ◽  
Adult Age ◽  
Graft Versus Host ◽  
Risk Of Death ◽  
Biomarker Analysis

Abstract Assessment of prognostic biomarkers of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) in the pediatric age group is lacking. To address this need, we conducted a prospective cohort study with 415 patients at 6 centers: 170 were children age 10 years or younger and 245 were patients older than age 10 years (both children and adults were accrued from 2013 to 2018). The following 4 plasma biomarkers were assessed pre-HCT and at days +7, +14, and +21 post-HCT: stimulation-2 (ST2), tumor necrosis factor receptor 1 (TNFR1), regenerating islet–derived protein 3α (REG3α), and interleukin-6 (IL-6). We performed landmark analyses for NRM, dichotomizing the cohort at age 10 years or younger and using each biomarker median as a cutoff for high- and low-risk groups. Post-HCT biomarker analysis showed that ST2 (>26 ng/mL), TNFR1 (>3441 pg/mL), and REG3α (>25 ng/mL) are associated with NRM in children age 10 years or younger (ST2: hazard ratio [HR], 9.13; 95% confidence interval [CI], 2.74-30.38; P = .0003; TNFR1: HR, 4.29; 95% CI, 1.48-12.48; P = .0073; REG3α: HR, 7.28; 95% CI, 2.05-25.93; P = .0022); and in children and adults older than age 10 years (ST2: HR, 2.60; 95% CI, 1.15-5.86; P = .021; TNFR1: HR, 2.09; 95% CI, 0.96-4.58; P = .06; and REG3α: HR, 2.57; 95% CI, 1.19-5.55; P = .016). When pre-HCT biomarkers were included, only ST2 remained significant in both cohorts. After adjustment for significant covariates (race/ethnicity, malignant disease, graft, and graft-versus-host-disease prophylaxis), ST2 remained associated with NRM only in recipients age 10 years or younger (HR, 4.82; 95% CI, 1.89-14.66; P = .0056). Assays of ST2, TNFR1, and REG3α in the first 3 weeks after HCT have prognostic value for NRM in both children and adults. The presence of ST2 before HCT is a prognostic biomarker for NRM in children age 10 years or younger allowing for additional stratification. This trial was registered at www.clinicaltrials.gov as #NCT02194439.

Predicting Steroid Refractroy Acute Gastrointestinal (GI) Acute Graft Versus Host Disease (AGVHD) by Assessment of Crypt Loss at Diagnosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2895-2895
Author(s):  
Joshua Melson ◽  
Ali Keshavarzian ◽  
Shriram Jakate ◽  
Sally Arai ◽  
Stephanie A. Gregory ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Risk Of Death ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Acute graft versus host disease accounts for most of the treatment failures after an allogeneic stem cell transplantation. The prognosis of patients with steroid refractory acute graft versus host disease is poor with conventional treatment. Early identification of patients with steroid refractory acute graft versus host disease may improve the transplant outcomes. Crypt loss has been associated with the severity of disease in patients with inflammatory bowel disease. It is also found in patients with acute gastrointestinal graft versus host disease with unknown clinical significance. In an attempt to evaluate the significance of crypt loss in patients with acute gastrointestinal graft versus host disease, we conducted a retrospective study on 22 consecutive post allogeneic stem cell transplant patients in our institution that underwent colonoscopy and colonic biopsy. In this study, crypt loss was graded and correlated with clinical parameters of disease severity including stool volume, endoscopic appearance, response to graft versus host disease treatment and one year mortality attributed to graft versus host disease. All the biopsies were reviewed by one of the co-authors (Shriram Jakate, M.D.). Twenty two consecutive patients who were treated for gastrointestinal graft versus host disease following stem cell transplantation were studied. Crypt loss was present in 16/22 cases and in 10/22 cases crypt loss was determined to be severe by the presence of contiguous areas of crypt loss. In those with severe crypt loss 9/10 patients had daily stool volumes in excess of 1000 ml/day while only 3/6 in those with minimal crypt loss had this level of severe diarrhea. Patients with severe crypt loss were more likely to have a pathologic appearance at endoscopy and to require second-line therapy (i.e. steroid refractory acute graft versus host disease). The diarrhea of those with severe crypt loss was less likely to resolve even though it was more aggressively treated. Of the 10 patients with severe crypt loss, 5 (50%) died of graft versus host disease related causes. Conversely, only one of 12 patients (8%) with mild or no crypt loss had a death attributable to acute graft versus host disease. Our study shows that severe crypt loss predicts for severity of acute gastrointestinal graft versus host disease, response to treatment and more importantly steroid refractoriness. In addition, crypt loss severity is associated with an increased risk of death related to acute graft versus host disease. We conclude that the assessment of crypt loss at diagnosis may serve as a tool to identify patients with steroid refractory acute gastrointestinal graft versus host disease and could be used to select patients for therapeutic trial in acute graft versus host disease.

Relationship of Harvest CD34+ and CD3+ Counts To Chronic Graft-Versus-Host Disease (cGVHD), Relapse and Survival Following Sibling Allogeneic Stem Cell Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1820-1820
Author(s):  
Andrea K. Kew ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Benjamin Djulbegovic
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Composite Endpoint ◽  
Cell Transplant ◽  
Host Disease ◽  
Graft Versus Host ◽  
Risk Of Death ◽  
Cell Counts ◽  
Increased Risk

Abstract G-CSF mobilized peripheral blood stem cells are increasingly used as a source of cells for sibling allogeneic transplantation. In comparison with bone marrow transplants (BMT), peripheral blood stem cell transplants (PBSCT) have been associated with increased chronic graft-versus-host disease (cGVHD). In order to examine the relationship between CD34+ and CD3+ counts and the development of cGVHD, we analyzed the outcome of patients from an international database of nine randomized trials comparing PBSCT and BMT. There were a total of 1111 patients: 305 patients developed extensive cGVHD, 261 limited cGVHD, 368 had no cGVHD and 177 did not have adequate information concerning cGVHD for analysis. We excluded patients with limited cGVHD because this can be a difficult diagnosis to make with certainty. We also excluded those without adequate data and thus the analysis is based on 673 patients (305 with extensive cGVHD and 368 with no cGVHD). There was no common baseline hazard for the development of extensive cGVHD among studies and thus the analysis was stratified by study. The primary outcomes were time to development of extensive cGVHD and time to the composite endpoint of death or relapse. Harvest CD34+ and CD3+ counts were analyzed as dichotomous variables based on the median cell counts. In the PBSCT group, the median CD34+ and CD3+ counts were 6.05 and 288.01×106/kg and in the BMT group, the median CD34+ and CD3+ counts were 2.89 and 32.79×106/kg respectively. As previously reported, there was an increased risk of developing extensive cGVHD with PBSCT compared to BMT (hazard ratio 1.77, 95% CI 1.39–2.23). The time to develop extensive cGVHD was not affected by the CD34+ or CD3+ count within either the PBSCT or BMT group. In addition, the composite endpoint of death or relapse was also not affected by either the CD34+ or CD3+ count in the PBSCT group. However, in the BMT group, a higher median CD3+ count was associated with an increased risk of death or relapse (p=0.04). Furthermore, a higher median CD34+ count was associated with a trend to a decreased risk of death or relapse (p=0.09). In summary, we confirm the higher risk of developing extensive cGVHD with PBSCT compared to BMT. In this analysis, we did not find a relationship between CD34+ and CD3+ counts and the risk of extensive cGVHD within either the PBSCT or BMT groups. However, our analysis suggests an association between higher median CD3+ counts and an increased risk of death or relapse in the BMT group. If this observation is confirmed, further studies are required to determine whether the higher CD3+ cell content of the marrow graft exerts a direct effect on the risk of relapse or death, or whether it is a surrogate for a less effective marrow harvest.

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