PS1540 MULTIPARAMETRIC PREDICTIVE SCORE FOR GRAFT VERSUS HOST DISEASE (GVHD) IN PATIENTS SUBMITTED TO ALLOGENEIC STEM CELLS TRANSPLANTATION (SCT)
Authors: A. Turra, N. Polverelli, F. Corvini, E. Morello, M. Malagola, F. Arena, M. Andreoli, A. Bertulli, M. Farina, F. Cattina, B. Rambaldi, L. Gandolfi, T. Zollner, E. Accorsi Buttini, S. Bernardi, C. Zanaglio, C. Foroni, F. Re, D. Russo
Journal: HemaSphere (2019)

Background: Graft versus host disease (GVHD) is the major cause of morbidity and mortality for patients submitted to allogeneic stem cell transplantation (SCT). Patient, donor and transplant characteristics, such as HLA-match, donor type, source of stem cells, female donor and age were described as predictors for acute (a) and chronic (c) GVHD. With the aim to identify possible predictors of GVHD for developing a risk score, we retrospectively analysed the above variables together with parameters of metabolic and endocrine functions. Aims: The predictors identified in this study can be easily obtained to elaborate a GVHD risk score and applied for a personalized risk-adapted therapy in order to obtain a global outcome improvement of SCT. Methods: Clinical, transplant characteristics and laboratory data were analysed in 330 patients (table 1) before SCT, at day +7,+14,+21,+28 and + 3 months. Clinical data were: disease status, patient and donor age, sex, blood group and CMV serology. Evaluated laboratory variables were liver and renal function, protein and lipid metabolism, endocrine system tests and autoimmune parameters. In a reduced number of patients we analyzed another group of nutritional parameters such as IGF-1. Univariate and multivariate analysis was carried out by Fine and Gray proportional hazard risk method. Results: In multivariate analysis, conditioning regimen including Total Body Irradiation (TBI) and Cyclophosphamide (HR 1,8; p = 0,011), HLA mismatch <8/8 (HR 1,68; p = 0,024) and urea <50 mg/dl at +7 day (HR 2,82; p = 0,035) were evidenced as predictors for aGVHD. Score values for each factor are 1, 1, and 1,5, respectively. Hence, the score, obtained by the sum of the three score values, ranged from 0 to 3,5 (figure 1). The cumulative incidence of aGVHD was 21, 37, 69% at day +30 and 37, 57, 75% (score 0–3,5) at day +100 in low, intermediate and high risk respectively (p = 0,0001). Previous aGVHD (HR 2,13; p = 0.00024) and no ATG prophylaxis (HR 1,86; p = 0,0018) resulted predictors for cGVHD, with score values of 1 and 1. The obtained score ranged from 0 to 2 (figure 1). The cumulative incidence of cGVHD was 12, 24, 47% at month +12 and 15, 30, 50% (score 0–2) at month +24 in low, intermediate and high risk respectively (p = 0,00001). Pre transplant IGF-1 > 150 ng/ml was related to an increased risk of aGVHD (HR 1,02; p = 0,0000011) and cGVHD in univariate analysis.Summary/Conclusion: Our study confirms the indipendent role of historical risk factors for GVHD such as TBI-based conditioning, HLA mismatch and no ATG use. Moreover our analysis based on clinical and routine-parameters, which are easily available in clinical practice, was used to develop a risk score for aGVHD and cGVHD (figure 1). Urea at day +7 may be an indipendent prognostic factor for aGVHD and levels depend on the balance between protein intake, endogenous catabolism and urinary excretion and may be a poor nutritional status index. IGF-1 has a supportive effect on the proliferation and differentiation of myeloid and lymphoid precursor cells and the increased value could be an additional trigger for lymphocyte subpopulations related to GVHD development. The biological relevance of our findings is under investigation and require a prospective validation. Deeper studies of the complex network between metabolic, endocrine and immune-system functions are warranted.