The prognostic impact of non-driver gene mutations and variant allele frequency in primary myelofibrosis.

Prognostic impact of non-MPN driver gene mutations in primary myelofibrosis. MIPSS70: Mutation-Enhanced International Prognostic Score System.

Recent advances in precision medicine for acute myeloid leukemia.

PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a heterogeneous disease, in which treatment response and patient survival are highly conditioned by the leukemia biology. The aim of this review is to summarize recent advances in AML classification, risk stratification models, measurable residual disease (MRD) and the increasing number of treatment options that are paving the way towards precision medicine in AML. RECENT FINDINGS: AML classification and risk stratification were recently updated by incorporating novel molecular markers that are important for diagnosis and outcome prediction. In addition, the impact of co-mutational patterns is under investigation and novel approaches using machine learning algorithms are starting to be used for individualized risk estimation. Molecular markers are also becoming useful in predicting response to non-intensive treatments. MRD informs of treatment response with high sensitivity, allowing dynamic patient risk assessment and early intervention. Finally, important advances were made in AML therapy, with an increasing number of targeted therapies becoming available and many novel treatment approaches being under development with promising early results. SUMMARY: A better understanding of AML biology is leading to improved risk stratification and important advances in treatments, which are allowing the development of precision medicine in AML at an unprecedented pace.

Machine Learning Improves Risk Stratification in Myelofibrosis: An Analysis of the Spanish Registry of Myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification.

Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study

ABSTRACT BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic-dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.

Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study.

BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic-dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.