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Although acute myeloid leukemia (AML) with NPM1 mut /FLT3-ITDneg is a low-risk entity, its relapse rate remains high. Out of 333 AML patients, 27 were NPM1 mut, and were analyzed in greater detail in order to find associations between clinical and molecular features and cumulative incidence of relapse. Next-generation sequencing (NGS) was performed on diagnosis and remission samples using two capture-based panels. The presence of the FLT3 D835 variant at diagnosis and a qPCR value of NPM1 mut ≥0.1% after induction chemotherapy were associated with an increased probability of relapse, especially if both conditions are present together. By contrast, patients in which the main clone found at diagnosis harbored NPM1 variant had a lower risk of relapse. Nineteen of the 85 variants found at diagnosis were detected by NGS in remission. AML Subgroup with NPM1 mut/FLT3-ITDneg is a heterogeneous entity, which can be further risk-stratified based on molecular biomarkers.

Introduction: Chimeric antigen receptor (CAR) T-Cell therapy is approved for relapse/refractory diffuse large B cell lymphoma (DLBCL) patients after two lines of therapy. Although it is an effective treatment, approximately 20-30% of patients have an early relapse. In this context, biomarkers that helps to identify those patients who will be refractory to this therapy are relevant. Cell-free DNA (cfDNA) has emerged as a new tool for non-invasive monitoring of patients with lymphoma, therefore the aim of this study was to evaluate dynamic cfDNA concentration in addition to other biomarkers (LDH, CRP, ferritin) before CAR T-cell infusion to detect early progressors. Methods: We selected 44 r/r DLBCL patients treated with CAR T-cell in our centre. Plasma samples were collected pre-apheresis (PA) and pre-infusion (PI)(∆cfDNA). Other biomarkers (LDH, CRP, Ferritin) were studied PA, pre-lymphodepletion (PL) and PI, tumour volume metabolic (TMV) are also studied. CfDNA were obtained from plasma using QIAamp® Circulating Nucleic Acid (Qiagen) and quantified by QuantiFluor dsDNA System (Promega). The Mann-Whitney test was used to compare differences between two independent quantitative variables . ROC analysis was conducted to determine the cut-off value of biomarkers. Cumulative incidence of progression (1 and 3 months) was calculated from the date of CAR T-cell infusion. Data analysis was performed using Stata. Results: Cumulative incidence of relapse at 1 month and 3 months was 20% and 30% respectively. The correlation between the progression (1 month, 3 months) and the different biomarkers is shown in Table 1. The CRP PL, CRP PI, LDH PI and ∆cfDNA (PI-PA, median time 41.5 days [range:31-107]) was correlated with early progression (1 month). No differences were found with progression at 3 months. The different cut-off for the biomarkers selected was 9 ng/mL for ∆cfDNA, 225 U/L for LDH and 1.35 mg/dL for CRP. Cumulative incidence of progression at 1 month was calculated for these biomarkers (figure 1): ∆cfDNA, HR: 4.3 (1.05-17), p=0.042; CRP PL: HR: 6.9 (1.5-31.1), p=0.012; CRP PI, HR: 11.2 (1.5-83), p=0.019 and LDH PI, HR: 3.4 (1-17) p=0.11. It should be noted that 83.3% (10/12) of the patients who progressed during the first month had at least one of the above variables. Conclusions: Our results highlight that increase in cfDNA higher than 9 ng/mL, CRP PL and PI >1.35 mg/dL and LDH PI > 225 U/L before CAR T-cell therapy may detect early progressors within the first month after treatment. Therefore, ∆cfDNA, CRP and LDH could be useful to identify patients who highly probable will not benefit from the CAR T infusion, in which another prior strategy could be considered in an attempt to control the disease. These results need to be confirmed with a larger cohort. Figure 1 Figure 1. Disclosures Bailén: Pfizer: Honoraria; Kite-Gilead: Honoraria; Gilead: Honoraria. Kwon: Gilead: Honoraria.

INTRODUCTION Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been established as a powerful treatment modality for patients with hematological malignancies. The graft-versus-leukemia effect, however, is strongly associated with the occurrence of graft-versus-host disease (GVHD) and subsequent transplant-related mortality (TRM). Several strategies are applied in order to prevent GVHD, the post-transplant cyclophosphamide (PT-Cy) is one of the most used in Haploidentical HSCT (Haplo-HSCT). Cyclophosphamide (CY) is an alkylating agent with antineoplastic and immunosuppressive activities. CY is metabolized by highly polymorphic enzymes to produce phosphoramide mustard which is a bifunctional DNA alkylating agent, is the therapeutically active metabolite. Thus, the aim of our study is to identity polymorphisms in the genes of the CY metabolism and correlated with complications post-HSCT (GVHD, TRM, veno-occlusive disease (VOD) or hemorrhagic cystitis (HC)). METHODS We selected 182 consecutive patients who received an Haplo-HSCT from 2007 to 2019. Eleven genes related to CY metabolism were analyzed (Table 1). The genotyping was performed in peripheral blood samples for recipient using an enrichment-capture custom gene panels (IDT probes) in a MiSeq platform (Illumina, USA). The bioinformatic analysis was carried out with BaseSpace software (Illumina, USA). Variants located in coding region and splicing sites were analyzed. We selected polymorphisms corresponding to read depth ≥30X in the canonical isoform with an allele frequency ≥0.4 and represented in at least 5% in our cohort. The collected clinical variables were age/gender recipient and donor, pathology, pretransplant status, conditioning regimen, total body irradiation, basal ferritin and CMV reactivation. Fisher test was used to compare the differences among groups. Statistical Package for the Social Sciences (SPSS, Chicago, USA) was used for statistical test. RESULTS The cumulative incidence rates for aGVHD of II-IV and III-IV grades at 100 days was 39% and 12% respectively. The cumulative incidence rates for cGVHD, moderate or severe cGVHD and TRM at 1000 days were 37%, 19% and 29%, respectively. Among the cases analyzed, 9% developed VOD and 25% HC. Patients who received ablative conditioning regimen presented a higher incidence of TRM (p=0.005). No other clinical data was associated with complications post HSCT. Forty polymorphisms were detected in 9 genes by bioinformatic analysis. The variants that presents some correlation (p Overall, polymorphisms related with decrease activity of enzymes that active cyclophosphamide (level lor active metabolite) were correlated with higher aGVHD, cGVHD, TRM and VOD (Table 1). On the other hand, polymorphisms associated with low activity in detoxification enzymes were correlated with higher toxicity (TRM). As described in bibliography, GSTM1 null allele were correlated with higher probability of developing VOD. CONCLUSIONS Genetic analysis of CY metabolism genes correlated with several post HSCT complications. The analyses of this variants before transplant could facilitate personalized risk and clinical management of patients undergoing Haplo HSCT. Results must validated in others cohorts of patients. Disclosures Kwon: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria.

INTRODUCTION Allogeneic haematopoietic stem cell transplant (allo-HSCT) could be the only curative therapy for patients with hematological malignancies due to graft effect against tumor. However, approximately 40% of patients develop post-transplantation complications such as acute graft-versus-host disease (aGVHD). Cytokines and their receptors are involved in regulatory and inflammatory processes that occur during GVHD. Therefore, the analysis of polymorphisms (SNPs) that affect the expression or activity of these genes could be used as biomarkers to predict the development of these complication. The aim of this study was to select new polymorphisms in cytokine genes (interleukins, chemokines and their receptors) to build models to predict the development of aGVHD after allo-HSCT from an HLA-identical sibling donor. METHODS We retrospectively selected 88 patients with hematological malignancies who received an allo-HSCT from an HLA-identical sibling donor from 2000 to 2015. A total of 176 pre-transplant recipient (R) and donor (D) peripheral blood samples were collected. The genotyping was performed using an enrichment-capture gene panels (include 132 genes (73 interleukins, 59 chemokines) in a HiSeq platform (Illumina, USA). The bioinformatic analysis was carried out with the GeneSystemssoftware (Sistemas Genómicos, Spain). Variants located in coding region, splicing sites, and UTR, 5'upstream and 3'downstream zones (+ 200pb) were analyzed. We selected polymorphisms corresponding to non-synonymous variants, represented in at least 5% of our cohort, with readings ≥30X in the canonical isoformwith an allele frequency ≥ 0.4. Fisher test was used to compare the differences among groups. Multiple logistic regression models were performed using combination of interleukins and chemokines polymorphisms selected previously that could be applied to clinical practice to predict aGVHD. The models with the highest AUC value, sensitivity and specificity value and the lowest number of genetic variants used were selected.Statistical Package for the Social Sciences (SPSS, Chicago, USA) was used for statistical test. RESULTS The cumulative incidence rates for aGVHD of grades II-IV and III-IV at 100 days after transplantation were 48.93% and 18.08%, respectively. The clinical variables (age, gender, pathology, stem cell source and previous transplantation) were not correlated with II-IV or III-IV aGVHD. However, patients who received ablative conditioning regimen presented a lower incidence of III-IV aGVHD (p= 0.041). Using filters defined previously, we detected 481 polymorphisms (350 coincident, 68 specific R and 63 for D) in the interleukins group. On the other hand, we detected 339 polymorphisms (267 coincident, 29 specific R and 43 for D) in the group of chemokines. Finally, 17 polymorphisms were selected in the interleukin group and 10 in the chemokine group for its correlation with the aGVHD (p We developed multiple logistic regression models for II-IV and III-IV aGVHD in interleukins and chemokines genes (Table 3). The identification of these 15 polymorphisms could help us to prevent the developing II-IV and III-IV aGVHD. CONCLUSIONS We have identified new genetic polymorphisms correlate with the risk of developing aGVHD after allo-HSCT from an HLA-identical sibling donor. Based on these data, we have developed a genetic score that encompasses polymorphisms of greater relevance. In this way, patients at greatest risk for developing this type of post-transplantation complication who could benefit from personalized management through immunosuppression and other drugs. Disclosures No relevant conflicts of interest to declare.