Electrocardiographic left ventricular strain pattern, ST-segment depression and atrial fibrillation at the time of diagnosis of systemic light chain amyloidosis: Incidence and clinical significance.

BACKGROUND: ST/T abnormalities recognized as electrocardiographic (ECG) left ventricular (LV) strain pattern are known as a marker of myocyte death and reduced survival. The purpose of this study was to determine whether ECG LV strain pattern, its components and atrial fibrillation (AF) predict lower survival at the time of diagnosis of systemic light chain (AL) amyloidosis. METHODS: 12­lead surface electrocardiogram (ECG), standard two-dimensional echocardiography, laboratory analyses were retrospectively evaluated within 2 months of diagnosis in 87 patients with biopsy-proven systemic AL amyloidosis from 2009 to 2017 in a single center. ECG strain pattern was defined as coexistence of ST-segment horizontal or downward sloping depression ≥0.05 mV at its most horizontal section and negative asymmetrical T-wave deeper than 0.1 mV in at least 1 of leads I,aVL,V1-V6. Patients with QRS >120 ms (BBB or major IVCD) were excluded from the analysis. RESULTS: Kaplan-Meier survival analysis revealed a 1.8-fold shorter overall survival (OS) at 2 years in the ECG strain (21% of participants) group (p = 0.0078), 2.0-fold shorter OS in the ST-segment depression (STd) (isolated and strain related as one group) (34% of participants) group (p < 0.0001), and 3.9-fold shorter OS in AF (23% of participants) group (p < 0.0001) compared with those without. Median survival of patients with STd and AF were and 13.0 (range 1-74) and 9.5 (range 1-74) months respectively. In univariate analysis STd and AF were stronger predictors of inferior OS than relative wall thickness, average E/e' ratio, and LV ejection fraction, but weaker predictors of OS than B-type natriuretic peptide. In multivariate analysis STd and AF lost significance after adjustment for age, gender, number of organs involved and BNP. CONCLUSIONS: ST-segment depression and AF were not significantly associated with reduced survival in AL amyloidosis at diagnosis.

Low incidence of ABL-class and JAK-STAT signaling pathway alterations in uniformly treated pediatric and adult B-cell acute lymphoblastic leukemia patients using MRD risk-directed approach - a population-based study.

BACKGROUND: ABL-class and JAK-STAT signaling pathway activating alterations have been associated with both a poor post-induction minimal residual disease (MRD) response and an inferior outcome in B-cell acute lymphoblastic leukemia (B-ALL). However, in most of the studies patients received non-uniform treatment. METHODS: We performed a population-based analysis of 160 (122 pediatric and 38 adult) Lithuanian BCR-ABL1-negative B-ALL patients who had been uniformly treated according to MRD-directed NOPHO ALL-2008 protocol. Targeted RNA sequencing and FISH analysis were performed in cases without canonical B-ALL genomic alterations (high hyperdiploids and low hypodiploids included). RESULTS: We identified ABL-class fusions in 3/160 (1.9%) B-ALL patients, and exclusively in adults (p = 0.003). JAK-STAT pathway fusions were present in 4/160 (2.5%) cases. Of note, P2RY8-CRLF2 fusion was absent in both pediatric and adult B-ALL cases. Patients with ABL-class or JAK-STAT pathway fusions had a poor MRD response and were assigned to the higher risk groups, and had an inferior event-free survival (EFS) / overall survival (OS) compared to patients without these fusions. In a multivariate analysis, positivity for ABL-class and JAK-STAT fusions was a risk factor for worse EFS (p = 0.046) but not for OS (p = 0.278) in adults. CONCLUSIONS: We report a low overall frequency of ABL-class and JAK-STAT fusions and the absence of P2RY8-CRLF2 gene fusion in the Lithuanian BCR-ABL1 negative B-ALL cohort. Future (larger) studies are warranted to confirm an inferior event-free survival of ABL-class/JAK-STAT fusion-positive adult patients in MRD-directed protocols.