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Background: Decreased hemoglobin concentration was reported to predict long term prognosis in patients various cardiovascular diseases including congestive heart failure and coronary artery disease. We hypothesized that hemoglobin levels may be useful for post discharge prognostication after the first episode of acute pulmonary embolism. Therefore, the aim of the current study was to evaluate a potential prognostic value of a decreased hemoglobin levels measured at admission due to the first episode of acute PE for post discharge all cause mortality during at least 2 years follow up. Methods: This was a prospective, single-center, follow-up, observational, cohort study of consecutive survivors of the first PE episode. Patients were managed according to ESC current guidelines. After the discharge, all PE survivors were followed for at least 24 months in our outpatient clinic. Results: During 2 years follow-up from the group of 402 consecutive PE survivors 29 (7.2%) patients died. Non-survivors were older than survivors 81 years (40–93) vs. 63 years (18–97) p < 0.001 presented higher sPESI 2 (0–4) vs. 1 (0–5), p < 0.001 driven by a higher frequency of neoplasms (37.9% vs. 16.6%, p < 0.001); and had lower hemoglobin (Hb) level at admission 11.7 g/dL (6–14.8) vs. 13.1 g/dL (3.1–19.3), p < 0.001. Multivariable analysis showed that only Hb and age significantly predicted all cause post-discharge mortality. ROC analysis for all cause mortality showed AUC for hemoglobin 0.688 (95% CI 0.782–0.594), p < 0.001; and for age 0.735 (95% CI 0.651–0.819) p < 0.001. A group of 59 subjects with hemoglobin < 10.5 g/dL showed mortality rate of 16.9% (OR for mortality 4.19 (95% CI 1.82–9.65), p-value < 0.00, while among 79 patients with Hb > 14.3 g/dL only one death was detected. Interestingly, patients in age > 64 years hemoglobin levels < 13.2 g/dL compared to patients in the same age but with >13.2 g/dL showed OR 3.6 with 95% CI 1.3–10.1 p = 0.012 for death after the discharge. Conclusions: Lower haemoglobin measured in the acute phase especially in patients in age above 64 years showed significant impact on the prognosis and clinical outcomes in PE survivors. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy (IC) is a challenge in clinical practice. Here we prospectively evaluated a novel low-intensity regimen consisting of low-dose cytarabine combined with cladribine (LD-AC+cladribine) for remission induction followed by LD-AC alone in the maintenance phase as the frontline treatment for elderly AML patients ineligible for IC. We included a cohort of 117 elderly patients in poor performance status or with significant comorbidities. High-risk or intermediate-risk cytogenetics were observed in almost 90% of patients. Treatment with LD-AC+cladribine led to the objective response rate of 54% and the median overall survival of 17.3 months in the responders group. The toxicity profile was predictable and infectious complications were the most common non-hematological adverse events. In conclusion, we found LD-AC+cladribine as a beneficial therapeutic option with an acceptable safety profile in the difficult-to-treat population of elderly AML patient ineligible for IC. Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC. [ABSTRACT FROM AUTHOR]

Telomeres are specialized nucleoprotein complexes, localized at the physical ends of chromosomes, that contribute to the maintenance of genome stability. One of the features of chronic myeloid leukemia (CML) cells is a reduction in telomere length which may result in increased genomic instability and progression of the disease. Aberrant telomere maintenance in CML is not fully understood and other mechanisms such as the alternative lengthening of telomeres (ALT) are involved. In this work, we employed five BCR-ABL1-positive cell lines, namely K562, KU-812, LAMA-84, MEG-A2, and MOLM-1, commonly used in the laboratories to study the link between mutation, copy number, and expression of telomere maintenance genes with the expression, copy number, and activity of BCR-ABL1. Our results demonstrated that the copy number and expression of BCR-ABL1 are crucial for telomere lengthening. We observed a correlation between BCR-ABL1 expression and telomere length as well as shelterins upregulation. Next-generation sequencing revealed pathogenic variants and copy number alterations in major tumor suppressors, such as TP53 and CDKN2A, but not in telomere-associated genes. Taken together, we showed that BCR-ABL1 kinase expression and activity play a crucial role in the maintenance of telomeres in CML cell lines. Our results may help to validate and properly interpret results obtained by many laboratories employing these in vitro models of CML. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe., Methods: We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection., Results: At the time of infection 51 patients (27.1%) were treated with Bruton tyrosine kinase inhibitor (BTKi), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) received venetoclax. In total, 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID-19. Patients with poor performance status (ECOG >1; p = 0.02), advanced age (>65 years; p = 0.04), low hemoglobin concentration (≤10 g/dl; p = 0.0001), low platelets (<100 × 109/L; p = 0.003), and elevated lactate dehydrogenase level (LDH; p = 0.014) had an increased risk of death due to COVID-19. Neither CLL treatment status (treatment naïve vs. treated) nor the type of CLL-directed treatment had impact on the SARS-CoV-2 related risk of death. The multivariate survival analysis showed that advanced age ( p = 0.009) and low platelet count ( p = 0.0001) were associated with significantly shorter patients' overall survival., Conclusions: SARS-CoV-2 infection in CLL patients is associated with poor outcome regardless of administered CLL-directed treatment.