Dataset Information

Longitudinal characterization of olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation.

ABSTRACT: Sepsis is an important cause of morbidity and mortality in pediatric patients. Increased expression of olfactomedin-4 (OLFM4), a glycoprotein contained within a subpopulation of neutrophils, has been associated with complicated course in sepsis. The factors that regulate OLFM4 expression are unknown. Here, we followed children undergoing bone marrow transplantation (BMT) to document the percentage of neutrophils that express OLFM4 over time. This population was selected because of the ability to observe nascent neutrophils following engraftment, perform frequent blood sampling, and the children are at high risk for clinical complications that may associate with changes in percentage of OLFM4+ neutrophils. We found a surprising degree of variability of OLFM4 expression between patients. In the weeks following initial neutrophil recovery we also saw great variability in OLFM4 expression within individual patients, indicating that multiple external factors may modify OLFM4 expression. We identified decreased expression of CD64 (a marker associated with response to infection), in OLFM4+ neutrophils. This is the first study to demonstrate fluctuation in OLFM4 expression within patients and provides insight into possible mechanisms for OLFM4 regulation in nascent neutrophils.

SUBMITTER: Stark JE

PROVIDER: S-EPMC7259555 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Longitudinal characterization of olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation.

Stark Julie E JE Opoka Amy M AM Fei Lin L Zang Huaiyu H Davies Stella M SM Wong Hector R HR Alder Matthew N MN

PloS one 20200529 5

Sepsis is an important cause of morbidity and mortality in pediatric patients. Increased expression of olfactomedin-4 (OLFM4), a glycoprotein contained within a subpopulation of neutrophils, has been associated with complicated course in sepsis. The factors that regulate OLFM4 expression are unknown. Here, we followed children undergoing bone marrow transplantation (BMT) to document the percentage of neutrophils that express OLFM4 over time. This population was selected because of the ability to ...[more]

PMID: 32470072

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Project description:Post-transplantation cyclophosphamide (PT-CY) is the most widely applied graft-versus-host disease (GVHD) prophylaxis regimen in T-cell replete haploidentical bone marrow transplantation (haplo-BMT). Although PT-CY has met with great success in the haplo-BMT arena by suppressing GVHD, patients without acute GVHD have high relapse rates. One strategy to reduce relapse rates being explored by others is a dosage reduction of PT-CY. We have taken a different approach in evaluating whether partially replacing PT-CY with post-transplantation bendamustine (PT-BEN) would be advantageous, an idea based on our preclinical research identifying several beneficial immunomodulatory properties of BEN. We therefore initiated and completed a Phase Ia trial to evaluate the progressive substitution of PT-CY with PT-BEN (ClinicalTrials.gov identifier NCT02996773). We compared outcomes between 13 patients with high-risk hematologic malignancies who received PT-CY/BEN and 31 contemporaneous haplo-BMT recipients treated with the same myeloablative conditioning regimens but receiving only PT-CY. We found that partial replacement of PT-CY with PT-BEN (PT-CY/BEN) on day +4 was well tolerated and associated with significantly earlier trilineage engraftment. We also report favorable trends toward significant improvements on univariate and multivariate analyses with PT-CY/BEN compared with PT-CY with respect to rates of chronic GVHD (hazard ratio [HR], .08; 95% confidence interval [CI], .005 to 1.11; P = .06), and GVHD-free relapse-free survival (GRFS) (HR, .22; 95% CI, .05 to .86; P = .039). Our human trial has now transitioned to Phase Ib, which will further evaluate the safety and potential benefits of PT-CY/BEN. Herein we also expand our pediatric, adolescent, and young adult experience to 31 patients, demonstrating overall survival, progression-free survival, and GRFS at 3 years of 85.6%, 76.1%, and 58.2%, respectively, in a largely racial/ethnic minority cohort. PT-CY/BEN appears to be a promising treatment option that requires further evaluation.

Dataset Information

Longitudinal characterization of olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation.

Publications

Longitudinal characterization of olfactomedin-4 expressing neutrophils in pediatric patients undergoing bone marrow transplantation.

Similar Datasets

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