Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study

PETHEMA (Programa Español de Tratamientos en Hematología) and GETH (Grupo Espa~nol de Trasplante Hematopoyético y Terapia Celular) Cooperative GroupsAcute myeloid leukemia (AML) with intermediate risk cytogenetics (IRcyto) comprises a variety of biological entities with distinct mutational landscapes that translate into differential risks of relapse and prognosis. Optimal postremission therapy choice in this heterogeneous patient population is currently unsettled. In the current study, we compared outcomes in IRcyto AML recipients of autologous (autoSCT) (n = 312) or allogeneic stem cell transplantation (alloSCT) (n = 279) in first complete remission (CR1). Molecular risk was defined based on CEBPA, NPM1, and FLT3-ITD mutational status, per European LeukemiaNet 2017 criteria. Five-year overall survival (OS) in patients with favorable molecular risk (FRmol) was 62% (95% confidence interval [CI], 50-72) after autoSCT and 66% (95% CI, 41-83) after matched sibling donor (MSD) alloSCT (P = .68). For patients of intermediate molecular risk (IRmol), MSD alloSCT was associated with lower cumulative incidence of relapse (P < .001), as well as with increased nonrelapse mortality (P = .01), as compared to autoSCT. The 5-year OS was 47% (95% CI, 34-58) after autoSCT and 70% (95% CI, 59-79) after MSD alloSCT (P = .02) in this patient subgroup. In a propensity-score matched IRmol subcohort (n = 106), MSD alloSCT was associated with superior leukemia-free survival (hazard ratio [HR] 0.33, P = .004) and increased OS in patients alive 1 year after transplantation (HR 0.20, P = .004). These results indicate that, within IRcyto AML in CR1, autoSCT may be a valid option for FRmol patients, whereas MSD alloSCT should be the preferred postremission strategy in IRmol patients.Supported by a Río Hortega academic clinical fellowship (CM19/00194) from the Instituto de Salud Carlos III, Spain (E.R.A.). Additional funding has been provided by CIBERONC grants to J.P.S. (CB16/12/00480), M.M.S. (CB16/12/00369) and B.V. (CB16/12/00233)

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.Depto. de MedicinaFac. de MedicinaTRUEInstituto de Salud Carlos IIIFundación CRIS Contra el CáncerInstituto de Investigación Hospital 12 de OctubreUnión Europeapu

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Monitorización de los pacientes con leucemia mieloide crónica en tratamiento con imatinib

Tesis doctoral inédita leÍda en la Universidad Autónoma de Madrid. Facultad de Medicina. Departamento de Medicina Fecha de lectura: 9 de Septiembre de 200

Estudio RAD-ICA: valor pronóstico de la radiografía de tórax obtenida en urgencias en pacientes con insuficiencia cardiaca aguda

Objective. To determine whether chest radiographs can contribute to prognosis in patients with acute heart failure (AHF). Methods. Consecutive patients with AHF were enrolled by the participating emergency departments. Radiographic variables assessed were the presence or absence of evidence of cardiomegaly and pleural effusion and the pulmonary parenchymal pattern observed (vascular redistribution, interstitial edema, and/or alveolar edema). We gathered variables for the AHF episode and the patient's baseline state. Outcomes were in-hospital and 1-year mortality; hospital stay longer than 7 days, and a composite of events within 30 days of discharge (revisit, rehospitalization, and/or death). Crude and adjusted hazard ratios were calculated for the 3 categories of radiographic variables. The variables were also studied in combination. Results. A total of 2703 patients with a mean (SD) age of 81 (19) years were enrolled; 54.5% were women. Cardiomegaly was observed in 1711 cases (76.8%) and pleural effusion in 992 (36.7%). A pulmonary parenchymal pattern was observed in all cases, as follows: vascular redistribution in 1672 (61.9%), interstitial edema in 629 (23.3%) and alveolar edema in 402 (14.9%). The adjusted hazard ratios showed that cardiomegaly lacked prognostic value. However, the presence of pleural effusion was associated with a 23% (95% CI, 2%-49%) higher rate of the 30-day composite outcome; in-hospital mortality was 89% (30%-177%) higher in the presence of alveolar edema, and 1-year mortality was 38% (14%-67%) higher in association with vascular redistribution. The results for the variables in combination were consistent with the results for individual variables. Conclusions: A diagnostic chest radiograph can also contribute to the prediction of adverse events. Pleural effusion is associated with a higher rate of events after discharge, and alveolar edema is associated with higher mortality

A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia.

The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high-risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo-SCT) and relapse-free interva

Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer

Background and Aims: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing. In this study, we aimed to identify potential genomic biomarkers of vinflunine response in mUC patient samples and potential management alternatives. Methods: Formalin-fixed paraffin-embedded samples of mUC patients (n = 23) from three university hospitals in Spain were used for genomic targeted-sequencing and transcriptome (using the Immune Profile panel by NanoString) analyses. Patients who received vinflunine after platinum-based chemotherapy failure were classified in non-responders (NR: progressive disease ≤ 3 months; n= 11) or responders (R: response ≥ 6 months; n = 12). Results: Genomic characterization revealed that the most common alteration, TP53 mutations, had comparable frequency in R (6/12; 50%) and NR (4/11; 36%). Non-synonymous mutations in KTM2C (4/12; 33.3%), PIK3CA (3/12; 25%) and ARID2 (3/12; 25%) were predominantly associated with response. No significant difference was observed in tumour mutational burden (TMB) between R and NR patients. The NR tumours showed increased expression of diverse immune-related genes and pathways, including various interferon gamma-related genes. We also identified increased MAGEA4 expression as a potential biomarker of non-responding tumours to vinflunine treatment. Conclusions: Our data may help to identify potential genomic biomarkers of response to vinflunine. Moreover, tumours refractory to vinflunine showed immune signatures potentially associated with response to ICB. Extensive validation studies, including longitudinal series, are needed to corroborate these findings