Both Engraftment syndrome (ES) and Graft-versus-Host disease (GvHD) are known as adverse events after hematopoietic stem cell transplantation (HSCT), contributing substantially to post-transplant morbidity and mortality [1], [2], [3], [4]. ES, an enigmatic complication, emerges during the neutrophil recovery phase of engraftment [5]. The pathogenesis of ES remains elusive, likely involving the release of various pro-inflammatory cytokines, products of neutrophils degranulation and oxidative metabolism, as well as systemic endothelial damage [3], [5]. In contrast, acute GvHD (aGvHD) is mainly caused by the immunological response of donor T cells. Activating of alloreactive T cells by cytokines and antigens from recipients in the early period after transplantation, is a critical trigger for aGvHD [6], [7]. These highlight the crucial role of cytokines in the immunological processes of both ES and aGvHD.

Currently, the lack of specific biomarkers hampers the timely identification of ES and aGvHD. ES is typically characterized by non-infectious fever, maculopapular rash, weight gain, capillary leak, non-cardiogenic pulmonary edema, as well as dysfunction of liver and kidney [5]. However, patients with aGvHD also exhibit clinical manifestations such as rash, diarrhea, and liver impairment [8], making the differential diagnosis between ES and aGVHD challenging. Moreover, the complex and incompletely understood pathogenesis of ES and aGvHD hinders their clear delineation. It remains controversial whether ES and aGvHD are variants of a single pathology, or if ES possesses distinct biology from aGvHD [5], [9], [10], [11]. Although ES and aGvHD share symptomatic and some clinical indicators, it is noteworthy that aGvHD predominantly affects patients who undergo allogeneic HSCT [12], while ES is observed in various transplant settings, including autologous ad allogeneic HSCTs [13], [14], [15]. This diagnostic challenge between ES and aGvHD, along with their intricate pathogenesis, impedes prompt and tailored interventions, demanding new indicators for early diagnosis of ES and timely therapeutic initiation, and thus a better post-transplant outcome as well.

Given the involvement of cytokines in the pathogenesis of ES and aGvHD, cytokines emerge as potential diagnostic biomarkers. Previous studies have reported alterations in cytokine profiles among ES [13], [14], [16], [17] or aGvHD patients [18], [19], [20], [21], yet disparities exist, probably arising from variations in diagnostic criteria for ES, cytokine detection methods, and patient demographics in these studies. In addition, studies simultaneously comparing cytokine profiles in ES and aGVHD are limited. Advancements in multi-cytokine detection technologies [22] provide an avenue to comprehensively explore cytokine profiles in HSCT patients. With this in mind, we systematically investigated plasma cytokine profiles in HSCT recipients experiencing isolated ES and/or aGvHD, aiming to correlate specific cytokine levels with differential ES and aGvHD diagnosis to expedite clinical interventions.