Table_2_Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation.doc (41 kB)

Table_2_Preliminary Results of a Combined Score Based on sIL2-Rα and TIM-3 Levels Assayed Early After Hematopoietic Transplantation.doc

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posted on 07.02.2020 by Salvatore Leotta, Giuseppe Sapienza, Maria Grazia Camuglia, Giuseppe Avola, Annalia Di Marco, Gaetano Moschetti, Angelo Curto Pelle, Uros Markovic, Giulio Antonio Milone, Alessandra Cupri, Oriana Bianco, Viviana Frontini, Andre Spadaro, Anna Elisa Marchese, Roberto Crocchiolo, Giuseppe Milone

Assays of cytokines in the plasma at the onset of graft-vs. -host disease (GVHD) can predict disease severity and treatment-related mortality (TRM); however, the optimal time during which cytokines should be tested and the specific panel of cytokines with the highest predictive ability remain unknown. We chose a predefined time point, 18 days after hematopoietic stem cell transplantation (HSCT), to measure the levels of six cytokines in the plasma: soluble interleukin-2 receptor alpha (sIL2-Rα), T-cell immunoglobulin domain and mucin domain-3 (TIM-3), suppression of tumorigenicity-2 (ST-2), intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). The study included 95 patients, who underwent allogeneic hematopoietic transplantation at our institution. Plasma levels of sIL2-Rα and TIM-3, measured as continuous data, had predictive value for overall survival (sIL2-Rα, p = 0.002; TIM-3, p = 0.0007), while TRM could be predicted by sIL2-Rα (p = 0.0005), IFN-gamma (p = 0.01), and IL-6 (p = 0.0001). No cytokine was associated with the risk of relapse. Patients were categorized into groups, according to cytokine thresholds determined by receiver operating characteristic curve analysis (sIL2-Rα ≤ or > 8,100 pg/ml; TIM-3 ≤ or > 950 pg/ml) and multivariate analysis was conducted. High levels of both TIM-3 and sIL2-Rα were significant predictors of poor survival [TIM-3 > 950 pg/ml: hazard ratio (HR) = 6.214 (95% CI 1.939–19.910), p = 0.002 and sIL2-Rα > 8.100 pg/ml: HR = 2.644 (95% CI 1.308–5.347), p = 0.006]. Using these cutoff thresholds, we constructed a composite scoring system that could distinguish three different groups of patients with varying rates of TRM: high risk, 41.7%; intermediate risk, 10.8%; and low risk, 7.1% (Gray's test: p = 0.001). If confirmed in a validation cohort, this composite scoring system could be used to guide the modulation of post-transplant immune suppressive therapy.

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