Acute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation ...status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.
Telomere dysfunction is a notable event observed in many cancers contributing to their genomic instability. A major factor controlling telomere stability is the human telomerase reverse transcriptase ...catalytic subunit (hTERT). Telomere shortening has been observed in multiple myeloma (MM), a plasma cell malignancy with a complex and heterogeneous genetic background. In the present study, we aimed to analyse telomere length and hTERT genetic variants as potential markers of risk and survival in 251 MM patients. We found that telomere length was significantly shorter in MM patients than in healthy individuals, and patients with more advanced disease (stage III according to the International Staging System) had shorter telomeres than patients with less advanced disease. MM patients with hTERT allele rs2736100 T were characterized with significantly shorter progression-free survival (PFS). Moreover, allele rs2736100 T was also found to be less common in patients with disease progression in response to treatment. hTERT rs2853690 T was associated with higher haemoglobin blood levels and lower C-reactive protein. In conclusion, our results suggest that telomere length and hTERT genetic variability may affect MM development and can be potential prognostic markers in this disease.
CD147 (basigin, BSG) is a membrane-bound glycoprotein involved in energy metabolism that plays a role in cancer cell survival. Its soluble form is a promising marker of some diseases, but it is ...otherwise poorly studied. CD147 is overexpressed in multiple myeloma (MM) and is known to affect MM progression, while its genetic variants are associated with MM survival. In the present study, we aimed to assess serum soluble CD147 (sCD147) expression as a potential marker in MM. We found that sCD147 level was higher in MM patients compared to healthy individuals. It was also higher in patients with more advanced disease (ISS III) compared to both patients with less advanced MM and healthy individuals, while its level was observed to drop after positive response to treatment. Patients with high sCD147 were characterized by worse progression-free survival. sCD147 level did not directly correlate with bone marrow CD147 mRNA expression. In conclusion, this study suggests that serum sCD147 may be a prognostic marker in MM.
Iron Dysregulation and Frailty Syndrome Zawadzki, Bartosz; Mazur, Grzegorz; Butrym, Aleksandra
Journal of clinical medicine,
11/2021, Volume:
10, Issue:
23
Journal Article
Peer reviewed
Open access
Patients with diagnosed frailty syndrome (FS) represent a special group of patients with chronic disease. In the classic definition, frailty syndrome includes such parameters as reduced muscle ...strength, subjective feeling of fatigue, unintentional weight loss, slow gait, and low physical activity. Frailty syndrome leads to an increased incidence of adverse events, such as falls, hospitalizations, and the need to place patients in care and health institutions associated with the loss of independence; frailty syndrome is also associated with an increased incidence of death. In European countries, the frequency of frailty syndrome in the geriatric population is estimated to be 17% with a range from 5.8% to 27%, and its incidence increases with age. A much higher percentage of frailty syndrome patients is also observed among hospitalized patients. The incidence of frailty syndrome is influenced by many socio-economic factors, but also medical factors. Materials and Methods: A total of 120 patients, >65 years of age, participated in the study. During the study, anthropometric measurements, surveys, laboratory determinations of basic biochemical parameters, and iron status were investigated; 5 mL of peripheral blood in EDTA was also collected for further laboratory tests of hepcidin and soluable transferrin receptor (sTfR) using ELISA. Then, the statistical analysis was performed based on survey and clinical data. Results: Among the patients >65 years of age, the incidence of frailty syndrome was 27.5%. It was found that its occurrence was associated with socio-economic factors, malnutrition, multiple morbidities, reduced muscle strength and gait speed, and polypharmacotherapy. The relationship between reduced iron concentration and the occurrence of frailty syndrome was confirmed. Conclusions: According to the analysis, it was found that a decrease in iron concentration was associated with frailty syndrome.
Infections represent one of the most frequent causes of death of higher-risk MDS patients, as reported previously also by our group. Azacitidine Infection Risk Model (AIR), based on red blood cell ...(RBC) transfusion dependency, neutropenia <0.8 × 109/L, platelet count <50 × 109/L, albumin <35g/L, and ECOG performance status ≥2 has been proposed based on the retrospective data to estimate the risk of infection in azacitidine treated patients.IntroductionInfections represent one of the most frequent causes of death of higher-risk MDS patients, as reported previously also by our group. Azacitidine Infection Risk Model (AIR), based on red blood cell (RBC) transfusion dependency, neutropenia <0.8 × 109/L, platelet count <50 × 109/L, albumin <35g/L, and ECOG performance status ≥2 has been proposed based on the retrospective data to estimate the risk of infection in azacitidine treated patients.The prospective non-intervention study aimed to identify factors predisposing to infection, validate the AIR score, and assess the impact of antimicrobial prophylaxis on the outcome of azacitidine-treated MDS/AML and CMML patients.MethodsThe prospective non-intervention study aimed to identify factors predisposing to infection, validate the AIR score, and assess the impact of antimicrobial prophylaxis on the outcome of azacitidine-treated MDS/AML and CMML patients.We collected data on 307 patients, 57.6 % males, treated with azacitidine: AML (37.8%), MDS (55.0%), and CMML (7.1%). The median age at azacitidine treatment commencement was 71 (range, 18-95) years. 200 (65%) patients were assigned to higher risk AIR group. Antibacterial, antifungal, and antiviral prophylaxis was used in 66.0%, 29.3%, and 25.7% of patients, respectively. In total, 169 infectious episodes (IE) were recorded in 118 (38.4%) patients within the first three azacitidine cycles. In a multivariate analysis ECOG status, RBC transfusion dependency, IPSS-R score, and CRP concentration were statistically significant for infection development (p < 0.05). The occurrence of infection within the first three azacitidine cycles was significantly higher in the higher risk AIR group - 47.0% than in lower risk 22.4% (odds ratio (OR) 3.06; 95% CI 1.82-5.30, p < 0.05). Administration of antimicrobial prophylaxis did not have a significant impact on all-infection occurrence in multivariate analysis: antibacterial prophylaxis (OR 0.93; 0.41-2.05, p = 0.87), antifungal OR 1.24 (0.54-2.85) (p = 0.59), antiviral OR 1.24 (0.53-2.82) (p = 0.60).ResultsWe collected data on 307 patients, 57.6 % males, treated with azacitidine: AML (37.8%), MDS (55.0%), and CMML (7.1%). The median age at azacitidine treatment commencement was 71 (range, 18-95) years. 200 (65%) patients were assigned to higher risk AIR group. Antibacterial, antifungal, and antiviral prophylaxis was used in 66.0%, 29.3%, and 25.7% of patients, respectively. In total, 169 infectious episodes (IE) were recorded in 118 (38.4%) patients within the first three azacitidine cycles. In a multivariate analysis ECOG status, RBC transfusion dependency, IPSS-R score, and CRP concentration were statistically significant for infection development (p < 0.05). The occurrence of infection within the first three azacitidine cycles was significantly higher in the higher risk AIR group - 47.0% than in lower risk 22.4% (odds ratio (OR) 3.06; 95% CI 1.82-5.30, p < 0.05). Administration of antimicrobial prophylaxis did not have a significant impact on all-infection occurrence in multivariate analysis: antibacterial prophylaxis (OR 0.93; 0.41-2.05, p = 0.87), antifungal OR 1.24 (0.54-2.85) (p = 0.59), antiviral OR 1.24 (0.53-2.82) (p = 0.60).The AIR Model effectively discriminates infection-risk patients during azacitidine treatment. Antimicrobial prophylaxis does not decrease the infection rate.DiscussionThe AIR Model effectively discriminates infection-risk patients during azacitidine treatment. Antimicrobial prophylaxis does not decrease the infection rate.
Lymphomas are one of the serious complications of the primary Sjörgen’s Syndrome (pSS). The aim of the study was to evaluate the frequency of lymphoma in pSS. The singe-center retrospective study ...included 198 Caucasian patients, who met diagnostic criteria for pSS. The type of lymphoproliferative disorder was classified according to the WHO 2016 classification. The mean time of observation, after pSS diagnosis, was 48 weeks. Focus score (FS) ≥ 1 was present in 85% of the patients, and anti-SSA antibodies were detected in 84%. Rheumatoid factor was detected in 130 (65%) patients. Mean disease activity index, according to EULAR Sjörgen’s Syndrome disease activity index (ESSDAI), was 8.3 points at the moment of pSS diagnosis. Complement C3 was decreased in 14% of the patients, while 10% showed reduced complement C4. Four patients (2%) were diagnosed with a lymphoma. Most of the patients were diagnosed with mucosa-associated lymphoid tissue lymphoma (MALT), in whom the tumour was located in the parotid gland, and in one patient the stomach was involved. Finally, one patient was diagnosed with a rare B-cell small lymphocytic lymphoma located in the lungs. In this article, we present detailed characteristics of each case. In analysed population the frequency of lymphoma in the course of pSS in patients with pSS is 2%. The variety of lymphoma types in pSS patients imposes individual monitoring in each patient at every check-up visit for disease activity.
MicroRNAs (miRNAs or miRs) are small molecules known to be involved in post-transcriptional gene expression. Many of them have been shown to influence risk for various diseases. Recent studies ...suggest that lower expression of miR-204, a gene coding for miRNA-204, is correlated with shorter survival in patients with acute myeloid leukaemia (AML). This observation prompted us to analyse the effect of two polymorphisms of the miR-204 gene, one in the upstream flanking region (rs718447 A > G) and the other inside the gene itself (rs112062096 A > G), both also in intron 3 of the TRPM3 gene.
The study was conducted on DNA samples isolated from AML patients (n = 95) and healthy individuals (n = 148), who were genotyped using the Light SNiP assays.
The miR-204 rs718447 GG homozygosity was found to constitute a risk factor associated with susceptibility to AML (73/95 vs 92/148, AML patients vs healthy controls, OR = 2.020, p = 0.017). Additionally, this genotype was more frequent in patients with subtypes M0-M1 in the French-American-British (FAB) classification as compared to patients with subtypes M2-M7 (23/25 vs 39/57, p = 0.026). We also found that presence of allele A was linked to longer survival of AML patients.
Our results show that polymorphism in miR-204 flanking region may constitute a risk and prognostic factor in AML.
Compared with World Health Organization-defined acute myeloid leukaemia (AML) not otherwise specified, patients with AML with myelodysplasia-related changes (AML-MRC) are generally older and more ...likely to have poor-risk cytogenetics, leading to poor response and prognosis. More than one-half of all older (≥65 years) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC.
We compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens (CCR; induction chemotherapy, low-dose cytarabine, or supportive care only) overall and within patient subgroups defined by cytogenetic risk (intermediate or poor) and age (65-74 years or ≥75 years). The same analyses were used to compare azacitidine with low-dose cytarabine in patients who had been preselected to low-dose cytarabine before they were randomized to receive azacitidine or CCR (ie, low-dose cytarabine).
Median overall survival was significantly prolonged with azacitidine (n = 129) versus CCR (n = 133): 8.9 versus 4.9 months (hazard ratio 0.74, 95%CI 0.57, 0.97). Among patients with intermediate-risk cytogenetics, median overall survival with azacitidine was 16.4 months, and with CCR was 8.9 months (hazard ratio 0.73 95%CI 0.48, 1.10). Median overall survival was significantly improved for patients ages 65-74 years treated with azacitidine compared with those who received CCR (14.2 versus 7.3 months, respectively; hazard ratio 0.64 95%CI 0.42, 0.97). Within the subgroup of patients preselected to low-dose cytarabine before randomization, median overall survival with azacitidine was 9.5 months versus 4.6 months with low-dose cytarabine (hazard ratio 0.77 95%CI 0.55, 1.09). Within the low-dose cytarabine preselection group, patients with intermediate-risk cytogenetics who received azacitidine had a median overall survival of 14.1 months versus 6.4 months with low-dose cytarabine, and patients aged 65-74 years had median survival of 14.9 months versus 5.2 months, respectively. Overall response rates were similar with azacitidine and CCR (24.8% and 17.3%, respectively), but higher with azacitidine versus low-dose cytarabine (27.2% and 13.9%). Adverse events were generally comparable between the treatment arms.
Azacitidine may be the preferred treatment for patients with AML-MRC who are not candidates for intensive chemotherapy, particularly patients ages 65-74 years and those with intermediate-risk cytogenetics.
This study was registered at clinicalTrials.gov on February 16, 2010 ( NCT01074047 ).
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