Abstract: CD38 is a surface receptor able to induce activation, proliferation, and survival of human and mouse lymphocytes; this molecule is expressed on the surface of both mature and immature B cells. In this work, the function of CD38 in the maturation of murine B lymphocytes in the spleen was analyzed. The results showed that CD38 is highly expressed on Transitional 2 (T2) B lymphocytes with an intermediate expression on Transitional 1 (T1) and mature follicular B cells (M). Correlating with a high expression of CD38, T2 cells are also larger and more granular than T1 or M B cells. T2 cells also showed high levels of other molecules, which indicate an activated phenotype. CD38 crosslinking induced proliferation and maturation of T2 B lymphocytes; in contrast, T1 subset died by apoptosis. Finally, CD38 stimulation of T2 B lymphocytes obtained from Btk-, Lyn-, or Fyn-deficient mice showed a defective differentiation; similarly, drugs interfering with PI3K or ERK decreased the proliferation or differentiation of this subset. This suggests that these molecules participate in the CD38 signaling pathway. As a whole, the results indicate that CD38 plays an important role in the regulation of B-cell maturation in the spleen.

Abstract: Despite idelalisib approval in relapsed follicular lymphoma (FL), a complete characterization of the immunomodulatory consequences of phosphatidylinositol 3-kinase δ (PI3Kδ) inhibition, biomarkers of response, and potential combinatorial therapies in FL remain to be established. Using ex vivo cocultures of FL patient biopsies and follicular dendritic cells (FDCs) to mimic the germinal center (n = 42), we uncovered that PI3Kδ inhibition interferes with FDC-induced genes related to angiogenesis, extracellular matrix formation, and transendothelial migration in a subset of FL samples, defining an 18-gene signature fingerprint of idelalisib sensitivity. A common hallmark of idelalisib found in all FL cases was its interference with the CD40/CD40L pathway and induced proliferation, together with the downregulation of proteins crucial for B–T-cell synapses, leading to an inefficient cross talk between FL cells and the supportive T-follicular helper cells (TFH). Moreover, idelalisib downmodulates the chemokine CCL22, hampering the recruitment of TFH and immunosupressive T-regulatory cells to the FL niche, leading to a less supportive and tolerogenic immune microenvironment. Finally, using BH3 profiling, we uncovered that FL–FDC and FL–macrophage cocultures augment tumor addiction to BCL-XL and MCL-1 or BFL-1, respectively, limiting the cytotoxic activity of the BCL-2 inhibitor venetoclax. Idelalisib restored FL dependence on BCL-2 and venetoclax activity. In summary, idelalisib exhibits a patient-dependent activity toward angiogenesis and lymphoma dissemination. In all FL cases, idelalisib exerts a general reshaping of the FL immune microenvironment and restores dependence on BCL-2, predisposing FL to cell death, providing a mechanistic rationale for investigating the combination of PI3Kδ inhibitors and venetoclax in clinical trials.

Abstract: Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379] ). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022] ). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.

Abstract: Abstract 2394 Poster Board II-371 Introduction: Genomic aberrations resulting in activation of oncogenes, inactivation of tumor suppressor genes or in the formation of novel chimeric genes are currently considered the main cause of the malignant phenotype of the AML cells. There is now increasing evidence that in addition to genetic aberrations, therapeutically reversible epigenetic events also play a critical role in the pathogenesis of human leukemias. Aims: We used a high-throughout methylation profiling to explore systematically the epigenomic variation underlying the biologic and clinical heterogeneity in AML. Patients and Methods: Using the Illumina GoldenGate Methylation Cancer Panel that spans 1,505 CpG loci, a detailed methylation profile of 116 AML patients distributed along all the cytogenetic prognostic subgroups was established. In addition, controls (BM and CB) and human progenitor cells expressing AML1/ETO, CBFβ/MYH11 or MLL/AF9 fusion proteins were analysed. Unsupervised and supervised hierarchical cluster were performed, and a selection of the most significantly differentially methylated loci (Δβ of at least 0.34 and FDR 〈 0.05) calculated as ψβ=(sample mean bvalue)–(control mean bvalue) was done. Candidate genes were validated by MSP in an independent cohort of 244 AML cases. Bisulphite sequencing and quantitative RT-PCR were carried in selected cases. Results: AML samples were correctly separated from BM controls and segregated in two main categories. While one of them showed a rather plane profile (Group I) similar to the one observed in the control bone marrow samples (only 7 probes showed a mean Δβ 〉 0.34), the other (Group II) presented dramatic changes with an aberrant methylation signature (24 probes showed a mean Δβ 〉 0.34). These two methylation categories showed significant differences in their distribution accross the prognosis cytogenetic groups. Eighty percent of the cases included on the adverse cytogenetic prognostic group clustered in one arm (Group I) and 80% of the cases included on the good prognosis cytogenetic group clustered in the other one (Group II). The normal karyotype (NK) cases were evenly distributed among the Groups I and II. No significant differences were observed for other variables as FLT3 mutational status. Kaplan-Meier analysis did not identified significant differences on the overall survival between the AML Group I and II. Focussing on the NK cases, two CpGs (from DBC1 and CDKN2B genes) were identified as statistically significant predictors of 5-year overall survival (OS). On the independent AML series, only the promoter methylation status of DBC1 retained statistical significance as predictor of the EFS and OS on NK cases. Expression studies showed a significant silencing of DBC1 on the aberrantly methylated samples. Taking advantage of our model of hematopoietic stem cells, stably transfected with the fusion proteins1-3 we observed that the epigenetic signature of the MLL leukemias is also observed on human progenitor cells fully transformed “in vitro” by this single oncogenic event. However, HSC expressing the AML1/ETO and CBFβ/MYH11 fusion proteins, which did not showed a full transformed phenotype, did not recapitulate the methylation signature observed on the AML primary cases. Conclusions: These results allowed us to conclude that: (1) The aberrant methylation of DBC1 gene among the NK AML cases is associated with a poor outcome. Therefore, the identification of patients with DNA epigenetic aberrations that have predictive value in determining survival should be essential in the forthcoming designs of clinical trials with demethylating agents. (2) A larger number of epigenetically modified genes is observed in the presence of single genetic abnormalities as t(8;21), t(15;17) or MLL rearrangements. However, a full leukemic transformation is require for the acquisition of a specific aberrant methylation profile, suggesting than the presence of fusion proteins as AML1/ETO or CBF/MYH11 is not sufficient to acquire a full aberrant methylation signature. 1. Wunderlich M, et al .et al Blood 2006;108:1690-7. 2. Wei J, et al . Cancer Cell 3. Mulloy JC et al Blood 2002;99:15-23. Disclosures: No relevant conflicts of interest to declare.

Abstract: Positron emission tomography (PET) with 18fluorine-fluoro-deoxyglucose (FDG) integrated with computed tomography (PET/CT) is a functional imaging technique helping us to assess bone marrow infiltration as well as unsuspected disease sites involving the bones and/or extramedullary sites. PET/TC has proved to be an independent prognostic factor for overall survival (OS) in symptomatic multiple myeloma (MM)(Zamagni,2011). However, its role in other monoclonal gammopathies (MG) is still a matter of debate. We have prospectively analyzed the contribution of baseline PET/TC in a unselected consecutive series of 158 patients with MG, including 88 MM, 7 MM smoldering (MMS), 11 Waldenstrm's macroglobulinemia (WM), 3 WM smoldering (WMS), 3 solitary bone plasmacytoma (SBP) and 46 monoclonal gammopathy of uncertain significance (MGUS). Patients with only palliative care were excluded. The pattern of bone marrow uptake on PET/TC was described as negative (NEG), diffuse involvement (DI) or focal lesions (FLs). Patients with more than 3 FLs as well as the presence of extramedullary disease (EMD) were analyzed separately. Overall survival (OS) was estimated by the Kaplan-Meier method. The main characteristics of PET/TC findings according to the type of MG are shown in Table 1. PET/TC was positive in 70 (79,5 %) of MM and 8 (72,7%) of WM. PET/TC was NEG in 100 % of MMS, WMS and SBP (except for the primary lesion). In MGUS, the findings reflect the clinical heterogeneity of this group: 19,6 % had bone disease (all but one case of probable inflammatory etiology), 17,4 % positive lymphadenopathy, 15,2 % lung disease (infection, fibrosis, pulmonary nodules), 6,5 % splenomegaly, 6,5 % liver disease, 6,5 % positive uptake in adrenal gland and other organs such as thyroid, stomach, colon or skin were affected less frequently. Median age of MM patients was 62 years (12-91), 51 men and 37 women (42%), the distribution according ISS was I (36,5 %), II (28,2 %) and III (35,3%). Among PET-positive MM, 39 (55,7 %) had 〉 3 FLs, 17 (24,3 %) 3 or less FLs and 14 (24,3 %) DI. Median OS was 40 months, not reached (NR) and 85,7 months, respectively (p=ns). Mean bone marrow plasma cells in the 〉 3 FLs group vs 3 or less FLs was 25 vs 12 (p=0,028). EMD was present in 13 (18,6 %) of PET-positive MM. Response with PET/CT was available in 32 patients: 18 achieved CR, 8 PR and 8 progressed. OS was NR for CR and PR vs 40 months (p 〈 0,0001). In WM, patients with NEG or FL had NR OS vs 26 months in those with DI (p=0,16). PET/CT is positive in the majority of MM and WM patients, helping to separate patients with true indolent disease. At baseline, PET/TC is a useful tool to improve prognostic assessment in patients with MG. MM with 〉 3 FLs or EMD at baseline had a trend towards lower OS. Negative serial PET/CT in MM is associated with favorable prognosis. Table SEQ Tabla \* ARABIC 1. Characteristics of main PET/TC findings according to the type of MG Type MM MMS WM WMS SBP MGUS n 88 7 11 3 3 46 Positive n /% 70/79,5 0 8/72,7 0 0 9/19,6 - 〉 3 FLs 39/55,7 0 0 0 0 0 -3 or 〈 FLs 17/24,3 0 1/12,5 0 0 1/2,2 -DI 14/20 0 5/62,5 0 0 1/2,2 -EMD 13/18,6 0 0 0 0 0 -Adenopathy 2/2,9 2/28,6 2/25 0 0 8/17,4 -Spleen 3/4,3 0 1/12,5 0 0 3/6,5 MG: Monoclonal gammopathy; MM: Multiple myeloma symptomatic; MMS: Smoldering myeloma; WM: Waldenstrm's macroglobulinemia; WMS: Smoldering Waldenstrm's macroglobulinemia; SBP: Solitary bone plasmocytoma; MGUS: Monoclonal gammopathy of uncertain significance; FL: Focal lesion; DI: Diffuse involvement; EMD: Extramedullary disease. Disclosures No relevant conflicts of interest to declare.

Abstract: INTRODUCTION MDS are a heterogeneous group, and it is necessary an adequate prognostic stratification in order to the best management. The new revised international prognostic scoring system (IPSS-R) has improved prognostic ability for survival and AML evolution comparing with the previous prognostic indexes. But, it is not clear the prognosis of patients included in the intermediate group, 20% of MDS, patients with a median OS of 3 years according to Greenberg et al, are they in the high or in the low risk category? The aims of the present study were to describe characteristics of patients included in this intermediate group of the IPSS-R in the Spanish MDS cohort and to identify which factors could have an impact on survival. A new score prognostic system (GESMDi score) in order to a better stratification should be proposed in this subset of patients that will be useful for determine the best therapeutic approach for them. METHODS: All patients were included in the GESMD, diagnosed of Primary MSD and Intermediate IPSS-R. The Statistical analyzes were performed using SPSS version 21, Cox models and Kaplan-Meier curves were used to demonstrate clinical outcomes. Regarding the new score proposed, GESMDi score, modeling of prognostic risk was based on multivariate analysis of survival time. Cox model for survival was built to derive the relative weights within the score. RESULTS: Data from 957 patients of 69 centers of GESMD were evaluated. Their median age was 73.9 years (p25/p75 66-80), 61.6% males (N=590), and median follow-up 21,4 months (p25-p75 de 11-41). Regarding WHO 2001 classification: 31% were RAEB-1, 21% CMML, 18% RCMD, 14% RAEB-2, 3% RCMD-RS, 3.1% RARS, 2.5% RA, 2% 5q-syndrome, 2% AML, 1% unclassified. Median hemoglobin at diagnosis was 9.8 g/dL (p25/p75:8.3-11.6), median bone marrow (BM) blasts 6% (p25/p75:3-8) and median platelet count 99x109/L (p25/p75:66-180). According to IPSS, 5% of patients were classified as low risk, 78% as intermediate-1, 16% as intermediate-2 and 1% as high risk. Cytogenetic were very good in 2% of patients, good in 76%, intermediate in 17%, poor in 5% and in 1% very poor. IPSS-R score classified patients in 3 different groups, with a punctuation of≤ 3.5 (35.6%), 〉 3.5 and ≤ 4 (35.8%) and 〉 4 and ≤ 4.5 (28.5%). Median OS was 30.1 months, the estimated 1-year and 2-y OS were 79.2% and 57.8%, respectively. In the univariate analysis for OS older age ( 〉 74y, p 〈 0.001), lower Hb level (≤9.5 g/dL, p 〈 0.001), WHO 2001 with excess of blasts classification (p=0.035), lower platelets level (≤30 x 109/L, p=0.01), PB blasts (yes, p=0.001), ferritine level ( 〉 500 ng/ml, p=0.002), and higher IPSS-R score ( 〉 3.5 and ≤ 4 and 〉 4 and ≤ 4.5, p=0.023 and p=0.004, figure 1) had a deleterious impact on survival. In the multivariate analysis, only age, Hb level, PB blast, ferritine level and IPSS-R value retained statistical significant impact on OS (table 1a). In the multivariate analysis, Hazard ratio, a new score system (GESMDi score) was established for all patients. Patients with adverse features were added points in order to stratify the risk of death: age 〈 74y and/or PB blasts (2 points) and Hb level ≤9.5 g/dL and/or ferritine level 〉 500 ng/ml and/or IPSS-R of 〉 3.5 (1 point), table 1a. The GESMDi score was performed in 685 patients with all data available and 7 groups of patients were defined with different median OS (p 〈 0.0001, table 1b). Two final categories were established according to the definition of risk from the Spanish MDS group, low risk patients (estimated OS 〉 30 months) and high risk patients ( 〈 30 months). Patients with scores between 0-3 (70.6% patients, me OS 41.1, 95CI 34.4-47.7) were in the low risk definition while patients with scores between 4-6 (29.3% patients, me OS 17.5 mo, 95CI 13.4-21.5) were classified as high risk patients (p 〈 0.0001, Figure 2). CONCLUSIONS: GESMDi score, a proposed prognostic score system from patients with intermediate IPSS-R, allow us to establish a better prognosis stratification in this heterogeneous MDS population. Treatment and management should be better established for those patients nowadays according to this novel stratification. Table 1 a) Univariate and multivariate analysis for OS among patients with Intermediate IPSS-R b) OS according to the GESMDi score proposed Table 1. a) Univariate and multivariate analysis for OS among patients with Intermediate IPSS-R b) OS according to the GESMDi score proposed Figure 1 OS according to IPSS-R value in the intermediate group (≤3.5, ≤4 and ≤4.5) Figure 1. OS according to IPSS-R value in the intermediate group (≤3.5, ≤4 and ≤4.5) Figure 2 OS according the GESMDi score proposed in the intermediate IPSS-R group: low and high risk patients (n=685) Figure 2. OS according the GESMDi score proposed in the intermediate IPSS-R group: low and high risk patients (n=685) Disclosures Del Cañizo: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astex: Membership on an entity's Board of Directors or advisory committees; janssen: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Díez Campelo:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astex: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Abstract: Mutations in the TLR/MYD88 pathway occur in 4% of patients with CLL, and they are the most frequent in young patients. TLR/MYD88 mutations in CLL patients confer a good outcome, which is similar to that of the age- and gender-matched healthy population.

Abstract: Abstract 4478 Background: The optimal therapy after transformation of follicular lymphoma into diffuse large B-cell lymphoma (DLBCL) is unknown. Most of retrospective registry data and phase II studies suggest a potential benefit of high-dose therapy and autologous transplantation (HDT-ASCT) for patients with transformed lymphoma (TL). Addition of rituximab to CHOP chemotherapy could improve survival in TL. However, the effect of prior rituximab-based therapy upon the efficacy of subsequent autologous stell cell transplantation (ASCT) in TL is still unknown. Patients and methods: We have identified the patients with follicular lymphoma who developed confirmed histological transformation to DLBCL treated with HDT-ASCT included in the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) Spanish registry between October 1994 and March 2011. Patients were divided into two groups, according to whether rituximab-based regimens were given (n = 28, ‘R+’ group) or not (n = 22, ‘R-’ group) at the time of transformation. Kaplan-Meier survival curves were estimated, and differences in survival curves between groups were assessed using the log-rank test. Results: Fifty patients (23 women) with a histological diagnosis of TL who underwent HDT-ASCT were included. Median age at transplantation was 55 years (range 32–70). Patients had received a median of 2 (range 1–5) chemotherapy regimens prior to ASCT. Median time from diagnosis of follicular lymphoma to transformation was 49 months (range 8–135). Age-adjusted International Prognostic Index (IPI) was 2 or 3 in 11 patients (22%). Disease status prior to ASCT was first complete remission in 4 patients (8%), second CR in 56% and active diseasein 14%: sensitive disease in 11 (22%) and refractory disease in 3 (6%) patients. Conditioning regimen consisted of BEAM in 92% of patients, BEAC in 4%, and cyclophosphamide /TBI in 4%. With a median follow-up of 61 months, estimated overall survival (OS) and progression-free survival (PFS) at 5 years after ASCT were 56.5% and 51.3%, respectively. No patients died of transplant-related mortality. Thirteen patients experienced relapse or progression after HD-ASCT; nine of these patients have died because of disease progression. By multivariate analysis three variables significantly influenced both OS and PFS: number of regimens prior to ASCT, disease status at transplant and achievement of response after HD-ASCT. Age-adjusted IPI at transformation had significant influence only on OS. Patients who did not receive rituximab-based regimens had similar characteristics to patients who received rituximab at transformation. Patients in the R+ group had similar 5-year PFS (48.2% vs 48.4%, P = 0.359) and 5-year overall survival (OS) (66.4% vs 67.2%, P = 0.607) compared to patients in the R- group (Figures 1 and 2). Eight out of 28 “R+” patients had not received rituximab prior to transformation; these patients had better PFS (69% vs 38%, p = 0.912) and OS at 5 years (74.1% vs 54.5%) compared to the 20 patients who were treated with rituximab prior to transformation, but the difference did not reach statistical significance (p 〉 0.1). Patients treated with rituximab-based regimens at any time prior HDT-ASCT had similar OS (70% versus 63.8% at 5 years, P = 0.697) and PFS (50% versus 44% at 5 years, P = 0.445) than patients who received chemotherapy alone before ASCT. Conclusion: Our results show that HDT-ASCT remains a valuable therapeutic choice for patients with histological confirmed TL since it allows a long-term disease control in a significant proportion of patients. The addition of rituximab to conventional chemotherapy after transformation does not appear to improve the outcomes of subsequent ASCT, although larger prospective studies are required. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction: Myeloid malignancies are clonal disorders of hematopoietic stem cells and include acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). Common biological markers have been described in the molecular pathogenesis, including gene mutations in splicing factors, epigenetic modifiers, transcription factors, signal pathways and tumor suppressors. These mechanisms have been associated with MDS and MPN progression to AML. Objectives: The main objective of this study is to identify differences in the mutational landscape of myeloid malignancies and describe mutation frequencies of genes and functional pathways in each neoplasm, as well as determine their clinical impact. Methods: This study involved a retrospective analysis of 430 patients with AML (209), MDS (106) and Philadelphia negative MPN (86) diagnosed in the Hospital Universitario 12 de Octubre (Spain). They were analyzed by a next generation sequencing (NGS)- panel for myeloid malignancies. The panel include 32 genes: CALR, ASXL1, EZH2, PHF6, DNMT3A 2, TET2, IDH1, IDH2, KDM6A, KMT2A, SF1, SF3A1, SF3B1, SRSF2, U2AF1, ZRSR2, PRPF40B, EPOR, FLT3, JAK2, KIT, SH2B3, MPL, CBL, HRAS, NRAS, KRAS, ETV6, RUNX1, VHL, TP53, PTEN. In addition, there were included 29 patients diagnosed with benign pathology that were referred to rule out MPN or congenital polyglobulia. Results: In the analyzed cohort we obtained a larger number of mutations in the more aggressive malignancies, AML and MDS. Mutations in epigenetic modifiers and signal pathways were the most frequent detected (31% and 24% respectively). The epigenetic modifiers were notably affected in AML (78%) and MDS (60.4%), whereas signal pathways were mutated more frequently in MPN (70.9%). Transcription factors, tumor suppressors and splicing factors mutations were more detected in AML and MDS (40%, 32%, 44% and 22%, 13%, 32% respectively). The mutation landscape obtained by genes was: Signal pathways: FLT3, NRAS, KIT, KRAS y SH2B3 were specially detected in AML (25%, 11%, 6%, 5% and 4% respectively). JAK2, CALR and MPL in MPN (38%, 15% and 6% respectively). Transcription factors: RUNX1, ETV6, PHF6, CEBPA and WT1 mutations were regularly observed in AML (21%, 6%, 6%, 6% and 5% respectively), and GATA1 in SMD (3.8%). Tumor suppressors: TP53 was particularly affected in AML (21%) and MDS (11%). Epigenetic modifiers: TET2 was notably mutated in MDS (32%), whereas ASXL1, DNMT3A, IDH2, IDH1 and EZH2 were in AML (21%, 21%, 17% 16% and 8% respectively). Splicing factors: SF3B1 was more frequently detected in MDS (18%) than AML (7%), whereas ZRSR2 presented a similar frequency in both pathologies (around 8%). U2AF1 was most commonly mutated in MPN (9%). SRSF2 was specially mutated in AML (23%). SF3A1 was altered in around 1%, similar in all three malignancies. With regard to survival studies, the presence of mutations in splicing factors (primarily in U2AF1) and its absence in signal pathways conferred an adverse outcome for overall survival (OS) in MPN. In MDS, gene mutations in tumor suppressors (especially TP53), U2AF1 splicing factor and EZH2 epigenetic modifier were associated with poor outcome. In our series of AML, gene mutations in tumor suppressors and TP53 were related to unfavorable prognosis in OS. Conclusion: The largest number of mutations and affected genes observed in AML suggest that leukemic transformation of MDS and MPN is conditioned by acquisition of new mutations. We observed different frequencies of mutations between AML, MDS and MPN that could guide the diagnostic and identify new targets of treatment. Further, some mutations have demonstrated differential prognostic impact. An extension of this study and the design of an algorithm with mutation data to elucidate a more accurate molecular prognosis will be presented at the meeting. This work has been financed thanks to the grant PI16/01225, PI 19/01518 and PI19/00730 from the Instituto de Salud Carlos III (Ministerio de Economia, Industria y Competititvidad) and cofinanced by the European Development Fund. Figure 1. Mutations detected (%) in AML, MDS and MPN classified by function. Table 1. Median overall survival of patients with MPN, MDS and AML according to gene state (mutated or not). Figure Disclosures No relevant conflicts of interest to declare.