Secondary acute myeloid leukemia (s‐AML) patients have a poor prognosis and currently the only curative therapy is allogeneic stem‐cell transplant (HSCT). However, we do not yet know whether transplantation is sufficient to reverse the poor prognosis compared to de novo AML patients. We analyzed survival after HSCT comparing a cohort of 58 patients with s‐AML versus 52 de novo patients who were transplanted between 2012 and 2020. Patients with s‐AML had worse event‐free survival (EFS) (p = 0.001) and overall survival (OS) (p < 0.001) compared to de novo AML due to an increased risk of relapse (p = 0.06) and non‐relapse mortality (p = 0.03). The main difference in survival was observed in patients who achieved complete remission (CR) before HSCT (EFS p = 0.002 OS and <0.001), regardless minimal residual disease (MRD) by |multiparametric flow cytometry cohorts. In patients transplanted with active disease (AD), the prognosis was adverse in both s‐AML and de novo AML groups (EFS p = 0.869 and OS p = 0.930). After excluding patients with AD, we stratified the cohort according to conditioning intensity, noticing that s‐AML who received MAC had comparable outcomes to de novo AML, but the survival differences remained among reduce intensity conditioning group. In conclusion, transplanted s‐AML patients have worse survival among patients in CR before HSCT, regardless of MRD level by flow cytometry compared to de novo AML. MAC patients had similar outcomes irrespective of leukemia ontogeny.
Introduction. The boundaries between MDS and AML are still a matter of debate. In the 2001 WHO Classification, the myeloblast count distinguishing AML and MDS was lowered from 30% to 20% of the bone marrow (BM) cells or peripheral blood (PB) leukocytes. It was justified on the basis that treating patients with 20-29% BM blasts with intensive chemotherapy showed a similar outcome to those with > 30% BM blasts. However, the better knowledge of the biology of both diseases is showing that in several cases AML and high risk MDS share identical genetic profiles, as it is well known in AML with myelodysplasia- related changes (AML-MRC). Currently there are new therapeutic options, less toxic, and suitable for elderly people.The threshold of 20% BM blast is artificial, but it is still the main criterion used in clinical trials and also in real life to discriminate patients that probably belong to the spectrum of the same biological entity. Treatment of patients with MDS or AML is widely based in this relatively arbitrary condition. Objective: To study if the threshold of 20% bone marrow blasts, distinguishing MDS with excess of blasts type 2 (MDS EB 2) and AML, is reproducible among different observers. Methods. 120 bone marrow samples from patients previously diagnosed with MDS-EB-2, AML or therapy-related myeloid neoplasms (t-MN) according to 2016 WHO classification were included. The diagnosis of MDS required cytogenetics and/or FISH, and the cases with AML should have been classified following the 2017 ELN recommendations, regarding immunophenotyping, cytogenetics and molecular biology. The design of the study was established to include cases with <40% BM blasts, WBC <25x109/L and less than 20% myeloblasts in peripheral blood. The proportion of samples from each category was not predefined. Specimens were collected from 12 hospitals and were evaluated by 12 morphologists. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. The interobserver concordance was evaluated using the Cohen kappa test. Results. Finally 116/120 samples were considered suitable for the study. Regarding 2016 WHO categories, 55 cases showed MDS EB-2, 44 AML-MRC, 8 t-MN, 4 AML- NOS, 2 NPM1-mutated AML, 2 RUNX1-RUNX1T1 AML, 1 BCR-ABL1+ AML. Next generation sequencing was performed in 79 cases. Discordance was observed in 34/116 cases (29.3%). 14 cases with MDS-EB2 (1 NPM1+) were classified as AML-MRC by the second observer, 16 AML cases as MDS EB-2, 3 MDS EB-2 as MDS- EB1 and 1 AML as MDS- EB1. The genetic and /or molecular profile of the discordant cases was heterogeneous. Regarding the threshold of 20% BM blasts, discrepancies were 31/116 (26.7%, I Kappa test = 0.46, moderate agreement). The agreement between MDS-EB-2 and AML-MRC, with discordance in 28/98 cases (28.6%), was moderate-fair (Kappa test= 0.42). Conclusion. The threshold of 20% BM blasts did not accurately separate AML from MDS EB-2. Particularly less concordance was seen for AML-MRC. Incorporation of genetic and molecular characteristics to the morphologic diagnosis is needed to optimize the definition of both entities. Acknowledgment: Angel Cedillo, Secretaría Técnica AMHH. Disclosures Font Lopez: GILEAD: Membership on an entity's Board of Directors or advisory committees; CELGENE-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Loscertales: Janssen, Abbvie, Astra-Zeneca, Beigene, Roche, Gilead: Consultancy; Janssen, Abbvie, Roche, Gilead: Speakers Bureau. Cedena: Janssen, Celgene and Abbvie: Honoraria.
Introduction: Response to chemotherapy treatment both by cytology and by more sensitive techniques such as cytometry is one of the most influential parameters in the survival of patients with Acute Myeloid Leukaemia (AML). Patients with detectable minimal residual disease (MRD) or those with active disease (AD) after induction or prior to allogeneic transplantation (HCST) represent a high-risk group. Objectives: to analyse the impact of disease burden before HSCT in terms of Overall Survival (OS) and Event Free Survival (EFS) in a group of patients who received HSCT in a single institution. We also analysed the influence of disease burden at the end of induction (considering best response after 1 or 2 cycles) and its impact on those patients in Cytological Remission (CR) with MRD <0.1% prior to transplantation. Methods: We analysed 103 patients who received HSCT in one centre between 2008 and 2020 in whom we knew disease status after induction and before HSCT. We divided the cohort into three groups according to preHSCT disease: Group 1) Patients in CR with MRD <0.1% by cytometry, Group 2) CR with MRD ≥0.1% and Group 3) patients with AD (≥5% blasts by cytology). We analysed post-transplant EFS and OS using the Kaplan Meier method and the Cumulative Incidence of Relapse (CIR) using Gray's test. Results: The baseline characteristics of the population are reflected in table 1. Median follow-up was 13 months (0-140). One-year EFS (1y-EFS) was 49%. One-year OS (1y-OS) was 57.5%, with a 1y-IAR of 27%. We first analysed the impact on post-transplant survival according to the different groups. Group 1 had significantly better EFS than Group 2 (p=0.04) and Group 3 (p<0.001) (Figure 1A). Regarding OS there was no difference between Group 1 and Group 2 (p=0.2) although it was significantly better than Group 3 (p<0.001) (Image 1B). IAR-1 was 14% vs 48% vs 50% (p<0.001) respectively. We subsequently analysed the impact on post-transplant survival according to the response to induction. Post-transplant EFS and OS were better in those in CR MRD- after induction compared to patients in CR with MRD+ (p=0.05 and p=0.002) as well as in patients with AD at the end of induction (p=0.002 and p=0.008). We stratified Group 1 according to the best response to induction (MRD- or MRD+/EA) and we performed an analysis according to the following groups: A) Patients with MRD- after induction and also before HSCT, B) Patients with MRD+/EA after induction achieving MRD- before HSCT. Comparing both groups there were no differences in either EFS (1y-EFS Group A 69% vs Group B 54%, p=0.5) or OS ( Group A 69% vs Group B 61%, p=0.8). Conclusions: Patients with pre-transplant AD or MRD+ are a high-risk group due to a high incidence of post-HSCT relapse. Although patients with AD or CR with MRD+ after induction have a worse prognosis, those who achieve MRD- before HSCT have a similar survival to the MRD- group from the start of chemotherapy. Figure 1 Figure 1. Disclosures Garcia-Gutiérrez: Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Novartis: Consultancy.
Objetivos. Evaluar el Consumo de Riesgo de Alcohol (CRA) en estudiantes de medicina españoles. Se estudia la influencia del sexo y la etapa académica en el CRA. Método. Estudio descriptivo transversal realizado en estudiantes de medicina, de 1 ° a 6 ° curso, de todo el territorio español. El AUDIT-C, con punto de corte para CRA de 5 para varones y 4 para mujeres, se administró en persona a estudiantes de una facultad de medicina española. Posteriormente se distribuyó el enlace al cuestionario a través de redes sociales. La participación fue voluntaria y anónima. Resultados. Se recogieron 1336 cuestionarios. 28.6% (n=382) varones y 71.4% (n=954) mujeres, edad media 21.7 ± 2.6 años. 44,9% (n=600) en etapa preclínica y 55,1% (n=736) en clínica. El 46% (n=614) puntuó para CRA. Se observó mayor CRA en etapa preclínica (p<.05). Hay diferencias en el patrón de consumo por razón de sexo (p<.05), no así en el CRA. Conclusiones. El CRA en estudiantes de Medicina es elevado. No se ha encontrado que el sexo influya en el CRA de forma significativa. El sexo influye en los patrones de consumo. Existe mayor CRA en preclínica. Se necesitan campañas de prevención y sensibilización desde la administración universitaria.
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