Clinical Significance of Haplo-Fever and Cytokine Profiling After Graft Infusion in Allogeneic Stem Cell Transplantation From Haplo-Identical Donors

Abstract

Allogeneic stem cell transplantation from haplo-identical donors (haplo-HSCT) has become a well-established therapeutic option for hematological malignancies. The fever of unknown origin (haplo-fever) early after the infusion of T cell repleted graft, which returned to normal right after post-transplantation cyclophosphamide (PTCy), is a unique clinical feature in patients undergoing haplo-HSCT. In the current study, the characteristics of haplo-fever and cytokine profiles during haplo-fever were retrospectively analyzed in a cohort of 37 patients undergoing T cell repleted haplo-HSCT with PTCy as graft versus host disease (GvHD) prophylaxis. In total, 33 patients (89.2%) developed haplo-fever from day 0 to day +7. Patients with high peak temperatures tended to have a lower incidence of chronic GvHD (cGvHD) ( p = 0.07), moderate to severe cGvHD ( p = 0.08), and superior GvHD and relapse-free survival (GRFS, p = 0.04). During the haplo-fever, there were significant increases in multiple cytokines, such as interferon gamma, interleukin (IL) 6, IL2, IL2 receptor, IL8, IL10, IL17, and tumor necrosis factor (TNF). The increases in IL2 receptor ( p = 0.037) and TNF ( p < 0.001) on day +4 were correlated with the lower risk of cGvHD. Increased TNF > 1.8055-fold on day +4 was the best predictive threshold for cGvHD, and was correlated with a lower incidence of cGvHD ( p < 0.001), moderate to severe cGvHD ( p = 0.003), and superior GRFS ( p < 0.001). These observations may reflect the early reactivation of donor T cells after haplo graft infusion, which would potentially be eliminated by PTCy. Further studies with larger independent cohorts of patients are warranted, to clarify the clinical significance of haplo-fever, and day +4 TNF as a potential biomarker to predict GvHD and GRFS.

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