Dataset Information

The soluble VCAM-1 level is a potential biomarker predicting severe acute graft versus host disease after allogeneic hematopoietic cell transplantation.

ABSTRACT:

Background

Severe graft versus host disease (GVHD) is the main reason for non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT). We investigated the serum protein profiles of patients who had undergone HCT to identify predictive biomarkers of severe acute GVHD (aGVHD).

Methods

Serum samples were collected for 30 patients from day - 7 to day + 14 of HCT. The serum levels of plasma beta2-microglobulin (β2-MG), soluble vascular cell adhesion molecule-1 (sVCAM-1), platelet factor 4, and TNFSF-14 were measured by ELISA as potential biomarkers following 310 cytokine profiling array.

Results

The median age of the study patients was 53.5 years (range, 19-69). All grade and grade 2-4 aGVHD developed in 21 (70.0%) and 17 (56.7%) patients, respectively. Compared with their baseline levels on day - 7, β2-MG and sVCAM-1 were significantly increased on day + 14 of the HCT procedure (P = 0.028 and P < 0.001, respectively). Patients with a grade 2-4 severe aGVHD showed a significantly higher sVCAM-1 level at baseline (day-7) and at day + 14, compared with the other group with a grade 1 aGVHD or no aGVHD (P = 0.028 and P = 0.035, respectively).

Conclusion

Higher sVCAM- levels at baseline and on day + 14 in HCT patients could be a significant predictive biomarker of severe aGVHD.

SUBMITTER: Heo SK

PROVIDER: S-EPMC9487033 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

The soluble VCAM-1 level is a potential biomarker predicting severe acute graft versus host disease after allogeneic hematopoietic cell transplantation.

Heo Sook-Kyoung SK Noh Eui-Kyu EK Lee Yoo Jin YJ Shin Yerang Y Kim Youjin Y Im Hyeon-Su HS Kim Hyeyeong H Koh Su Jin SJ Min Young Joo YJ Jo Jae-Cheol JC Choi Yunsuk Y

BMC cancer 20220920 1

<h4>Background</h4>Severe graft versus host disease (GVHD) is the main reason for non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT). We investigated the serum protein profiles of patients who had undergone HCT to identify predictive biomarkers of severe acute GVHD (aGVHD).<h4>Methods</h4>Serum samples were collected for 30 patients from day - 7 to day + 14 of HCT. The serum levels of plasma beta2-microglobulin (β2-MG), soluble vascular cell adhesion molecule-1 ( ...[more]

PMID: 36127634

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Project description:Chronic graft-versus-host disease (cGVHD) is major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD. We conducted a phase I/II trial in 57 patients to evaluate the safety and efficacy of ixazomib administration for cGVHD prophylaxis in patients undergoing allogeneic HCT. Oral ixazomib was administered on a weekly basis for a total of 4 doses, beginning days +60 through +90, to recipients of matched related donor (MRD, n = 25) or matched unrelated donor (MUD, n = 26) allogeneic HCT in phase II portion of the study, once the recommended phase II dose of 4 mg was identified in phase I (n = 6). All patients received peripheral blood graft and standard GVHD prophylaxis of tacrolimus and methotrexate. Ixazomib administration was safe and well tolerated, with thrombocytopenia, leukopenia, gastrointestinal complaints, and fatigue the most common adverse events (>10%). In phase II (n = 51), the cumulative incidence of cGVHD at 1 year was 36% (95% confidence interval [CI], 19% to 54%) in the MRD cohort and 39% (95% CI, 21% to 56%) in the MUD cohort. One-year cumulative incidence of nonrelapse mortality (NRM) and relapse was 0% and 20% (95% CI, 8% to 36%) in the MRD cohort, respectively. In the MUD cohort, the respective NRM and relapse rates were 4% (0% to 16%) and 34% (17% to 52%). The outcomes on the study were compared post hoc with contemporaneous matched Center for International Blood and Marrow Transplant Research (CIBMTR) controls. This post hoc analysis showed no significant improvement in cGVHD rates in both the MRD (hazard ratio [HR] = 0.85, P = .64) or MUD cohorts (HR = 0.68, P = .26) on the study compared with CIBMTR controls. B cell activating factor plasma levels were significantly higher after ixazomib dosing in those who remained cGVHD free compared with those developed cGVHD. This study shows that the novel strategy of short-course oral ixazomib following allogeneic HCT is safe but did not demonstrate significant improvement in cGVHD incidence in recipients of MRD and MUD transplantation compared with matched CIBMTR controls. This study is registered at www.clinicaltrials.gov as NCT02250300.

Dataset Information

The soluble VCAM-1 level is a potential biomarker predicting severe acute graft versus host disease after allogeneic hematopoietic cell transplantation.

Background

Methods

Results

Conclusion

Publications

The soluble VCAM-1 level is a potential biomarker predicting severe acute graft versus host disease after allogeneic hematopoietic cell transplantation.

Similar Datasets

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