Immune-Mediated Limbic Encephalitis after Haplo-Identical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclosphosphamide

Background: Immune-mediated limbic encephalitis (iLE) is a rare, but devastating complication that can develop after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the biologic characteristics and clinical outcomes of patients with ALE after haploidentical HSCT combined with post-transplant cyclophosphamide (PTCy). Methods: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent haploidentical HSCT with PTCy at Chungnam National University Hospital between June 2016 and May 2020. ALE was diagnosed by the typical finding of magnetic resonance imaging. We compared the characteristics of patients with and without ALE. Results: Of 35 patients, 4 (11.4%) patients had iLE. The median patient age was 54 years (range, 28-60 years; male : female ratio of 3:1). There were no differences in age, gender, body mass index, hematological disease, conditioning regimen according to iLE status. However, baseline interleukin-6 level before conditioning chemotherapy was higher in patients with iLE than those without iLE [median (range), IL-6; 161.16(103.4 - 199.1) pg/mL vs. 33.78769( 2.1 - 59.1) pg/mL, p < 0.001]. And, Serum IL-6, interferon (IFN)-γ and tumor-necrosis factor (TNF)-α level on day 3 after HSCT was significantly higher in patients with iLE [median (range), IL-6; 355.8 (305.8 - 399.6) pg/mL vs. 63.47 (6.5 - 127.2) pg/mL, p < 0.001/ IFN-γ; 15.045 (6.342 - 29.341) pg/mL vs. 1.602 (0 - 4.036) pg/mL, p = 0.0093 / TNF-α; ; 21.019 (13.268 - 34.138) pg/mL vs. 7.637 (0 - 13.938) pg/mL, p = 0.0205 ]. Patients with iLE had a higher incidence of veno-occlusive disease (VOD) [2 of 4 (50%) vs. 3 of 31 (9.7%), p = 0.030]. The population of naïve regulatory T cells were higher in iLE patient group on day 3 after HSCT than non-iLE group. Overall survival was significantly shorter in patients with iLE [median, 1.5 months, 95% CI, 1.45 - 2.05 vs. 11.0 months, 95% CI, 8.2 - 13.7, p = 0.001]. Conclusion: Patients with high serum interleukin-6 level on baseline & post-transplant day 3, who underwent haploidentical HSCT with PTCy need to be aware of developing iLE.