Novel Biomarkers for Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Oct 5

PMID 33013836

Citations 8

Authors

Sophia Chen

Robert Zeiser

Affiliations

Soon will be listed here.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established curative treatment for various malignant hematological diseases. However, its clinical success is substantially limited by major complications including graft-vs.-host disease (GVHD) and relapse of the underlying disease. Although these complications are known to lead to significant morbidity and mortality, standardized pathways for risk stratification of patients undergoing allo-HSCT are lacking. Recent advances in the development of diagnostic and prognostic tools have allowed the identification of biomarkers in order to predict outcome after allo-HSCT. This review will provide a summary of clinically relevant biomarkers that have been studied to predict the development of acute GVHD, the responsiveness of affected patients to immunosuppressive treatment and the risk of non-relapse mortality. Furthermore, biomarkers associated with increased risk of relapse and subsequent mortality will be discussed.

Citing Articles

Inflammatory pathways and anti-inflammatory therapies in sickle cell disease.

Tozatto-Maio K, Ros F, Weinlich R, Rocha V Hemasphere. 2024; 8(12):e70032.

PMID: 39698332 PMC: 11655128. DOI: 10.1002/hem3.70032.

Galectin-3 predicts acute GvHD and overall mortality post reduced intensity allo-HCT: a BMT-CTN biorepository study.

McCarthy P, Attwood K, Liu X, Chen G, Minderman H, Alousi A Bone Marrow Transplant. 2023; 59(3):334-343.

PMID: 38110620 PMC: 10961739. DOI: 10.1038/s41409-023-02168-0.

Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib.

Volkel S, Tarawneh T, Sacher L, Bhagwat A, Karim I, Mack H Front Med (Lausanne). 2023; 10:1176427.

PMID: 37293294 PMC: 10244732. DOI: 10.3389/fmed.2023.1176427.

Inflammatory CD4/CD8 double-positive human T cells arise from reactive CD8 T cells and are sufficient to mediate GVHD pathology.

Hess N, Turicek D, Riendeau J, Mcilwain S, Guzman E, Nadiminti K Sci Adv. 2023; 9(12):eadf0567.

PMID: 36961891 PMC: 10038349. DOI: 10.1126/sciadv.adf0567.

High Expression Is a Molecular Predictor of Post-Transplant Survival of Patients with Acute Myeloid Leukemia.

Rojas C, Costa-Neto A, Pereira-Martins D, Le D, Sternadt D, Weinhauser I Cancers (Basel). 2023; 15(1).

PMID: 36612292 PMC: 9818450. DOI: 10.3390/cancers15010296.

References

Elorza I, Palacio C, Dapena J, Gallur L, Sanchez de Toledo J, Diaz de Heredia C . Relationship between minimal residual disease measured by multiparametric flow cytometry prior to allogeneic hematopoietic stem cell transplantation and outcome in children with acute lymphoblastic leukemia. Haematologica. 2010; 95(6):936-41. PMC: 2878791. DOI: 10.3324/haematol.2009.010843. View

Ranganathan P, Ngankeu A, Zitzer N, Leoncini P, Yu X, Casadei L . Serum miR-29a Is Upregulated in Acute Graft-versus-Host Disease and Activates Dendritic Cells through TLR Binding. J Immunol. 2017; 198(6):2500-2512. PMC: 5340605. DOI: 10.4049/jimmunol.1601778. View

Harris A, Ferrara J, Braun T, Holler E, Teshima T, Levine J . Plasma biomarkers of lower gastrointestinal and liver acute GVHD. Blood. 2012; 119(12):2960-3. PMC: 3327467. DOI: 10.1182/blood-2011-10-387357. View

Wasch R, Bertz H, Kunzmann R, Finke J . Incidence of mixed chimaerism and clinical outcome in 101 patients after myeloablative conditioning regimens and allogeneic stem cell transplantation. Br J Haematol. 2000; 109(4):743-50. DOI: 10.1046/j.1365-2141.2000.02110.x. View

Liu X, Yue Z, Cao Y, Taylor L, Zhang Q, Choi S . Graft-Versus-Host Disease-Free Antitumoral Signature After Allogeneic Donor Lymphocyte Injection Identified by Proteomics and Systems Biology. JCO Precis Oncol. 2019; 3. PMC: 6690359. DOI: 10.1200/po.18.00365. View

Hubel K, Cremer B, Heuser E, Pogge von Strandmann E, Hallek M, Hansen H . A prospective study of serum soluble CD30 in allogeneic hematopoietic stem cell transplantation. Transpl Immunol. 2010; 23(4):215-9. DOI: 10.1016/j.trim.2010.07.001. View

Waterhouse M, Samek E, Torres M, Bertz H, Finke J . Diagnostic utility of a soluble cytokeratin 18 assay for gastrointestinal graft-vs.-host disease detection. Clin Chem Lab Med. 2011; 49(10):1695-7. DOI: 10.1515/CCLM.2011.644. View

Sangle N, Perkins S . Core-binding factor acute myeloid leukemia. Arch Pathol Lab Med. 2011; 135(11):1504-9. DOI: 10.5858/arpa.2010-0482-RS. View

Zaid M, Wu J, Wu C, Logan B, Yu J, Cutler C . Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT. Blood. 2016; 129(2):162-170. PMC: 5234220. DOI: 10.1182/blood-2016-08-735324. View

10.

Zeiser R, Blazar B . Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017; 377(22):2167-2179. PMC: 6034180. DOI: 10.1056/NEJMra1609337. View

11.

Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars F, Al Hinai A, Zeilemaker A . Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N Engl J Med. 2018; 378(13):1189-1199. DOI: 10.1056/NEJMoa1716863. View

12.

Wang Y, Zhao X, Ye X, Luo H, Zhao T, Diao Y . Plasma microRNA-586 is a new biomarker for acute graft-versus-host disease. Ann Hematol. 2015; 94(9):1505-14. DOI: 10.1007/s00277-015-2414-z. View

13.

. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69(3):89-95. DOI: 10.1067/mcp.2001.113989. View

14.

Lamba R, Abella E, Kukuruga D, Klein J, Savasan S, Abidi M . Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival. Leukemia. 2004; 18(10):1681-6. DOI: 10.1038/sj.leu.2403468. View

15.

Fujimori Y, Takatsuka H, Takemoto Y, Hara H, Okamura H, Nakanishi K . Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol. 2000; 109(3):652-7. DOI: 10.1046/j.1365-2141.2000.02095.x. View

16.

Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R . Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med. 2020; 382(19):1800-1810. DOI: 10.1056/NEJMoa1917635. View

17.

August K, Chiang K, Bostick R, Flanders W, Waller E, Langston A . Biomarkers of immune activation to screen for severe, acute GVHD. Bone Marrow Transplant. 2010; 46(4):601-4. DOI: 10.1038/bmt.2010.165. View

18.

Wingard J, Majhail N, Brazauskas R, Wang Z, Sobocinski K, Jacobsohn D . Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011; 29(16):2230-9. PMC: 3107742. DOI: 10.1200/JCO.2010.33.7212. View

19.

Paczesny S, Krijanovski O, Braun T, Choi S, Clouthier S, Kuick R . A biomarker panel for acute graft-versus-host disease. Blood. 2008; 113(2):273-8. PMC: 2615645. DOI: 10.1182/blood-2008-07-167098. View

20.

Frick M, Chan W, Arends C, Hablesreiter R, Halik A, Heuser M . Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2018; 37(5):375-385. DOI: 10.1200/JCO.2018.79.2184. View