Proinflammatory cytokines as potential risk factors of acute graft-versus-host disease and infectious complications after allogeneic hematopoietic stem cell transplantation

Malwina Rybicka-Ramos; Miroslaw Markiewicz; Aleksandra Suszka-Switek; Ryszard Wiaderkiewicz; Sylwia Mizia; Monika Dzierzak-Mietla; Krzysztof Bialas

Proinflammatory cytokines as potential risk factors of acute graft-versus-host disease and infectious complications after allogeneic hematopoietic stem cell transplantation

Am J Blood Res. 2021 Apr 15;11(2):149-156. eCollection 2021.

Authors

Malwina Rybicka-Ramos¹, Miroslaw Markiewicz², Aleksandra Suszka-Switek³, Ryszard Wiaderkiewicz³, Sylwia Mizia⁴, Monika Dzierzak-Mietla⁵, Krzysztof Bialas⁶

Affiliations

¹ Specialist Hospital No. 1 in Bytom, Department of Hematology Bytom, Poland.
² University of Rzeszow, College of Medical Sciences, Institute of Medical Sciences, Department of Hematology Rzeszow, Poland.
³ School of Medicine in Katowice, Medical University of Silesia, Department of Histology and Embryology Katowice, Poland.
⁴ Faculty of Health Science, Wroclaw Medical University, Department of Public Health, Department of Organization and Management Wroclaw, Poland.
⁵ Maria Sklodowska-Curie National Research Institute of Oncology, Department of Bone Marrow Transplantation and Hematooncology Gliwice, Poland.
⁶ SPSK-M Hospital, Department of Hematology and Bone Marrow Transplantation Katowice, Poland.

PMID: 34079628
PMCID: PMC8165716

Abstract

Objective: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with a risk of graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is related to T-lymphocytes, which identify alloantigens on host antigen-presenting cells, induce production of interferon (IFN) gamma and interleukin (IL)-2, recruit immune effector cells and destroy tissues and organs.

Material and methods: The study involved 62 patients, 30 (48%) men and 32 (52%) women [median age 49.5; (19-68) years] after myeloablative conditioning (MAC) n = 26 (42%) or reduced intensity conditioning (RIC) n = 36 (58%) therapy before allo-HSCT from a sibling (n = 12) or unrelated (n = 50) donor due to acute myeloid leukemia (AML). All patients received standard immunosuppressive therapy with cyclosporine A and methotrexate plus pre-transplant anti-thymocyte globulin in the unrelated transplant setting. Blood samples were collected pre-transplant before the start of and after conditioning therapy (1 day pre-transplant) and 2, 4, 6, 10, 20, 30 days following allo-HSCT. The analysis of potential risk factors included IL-2 and IFN-gamma concentrations, patients' age, the use of MAC/RIC and CR/non-CR status before transplantation.

Results: The statistical analysis revealed that independent risk factors for aGvHD included non-CR status before allo-HSCT [odds ratio (OR) = 10.52, P = 0.040], the use of MAC [hazard ratio (HR) = 4.80, P = 0.007] and a high level of IFN-gamma on day 6 post-transplant (HR = 1.03, P = 0.032). MAC was also the independent risk factor for infectious complications (OR = 4.04, P = 0.024).

Conclusion: A high level of IFN-gamma on day 6 post-transplant, non-CR status before allo-HSCT and the use of MAC are independent risk factors for aGvHD. MAC is also the independent risk factor of infectious complications.

Keywords: IFN-gamma; acute graft-versus-host disease; allogeneic stem cell transplantation; infectious complications; myeloablative conditioning therapy.