Browsing by Author "Djunic, Irena (23396871100)"

The treatment of chronic lymphocytic leukemia (CLL) consists of the continuous use of Bruton tyrosine kinase inhibitors (BTKis) such as ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib, or Bcl-2 inhibitors, such as venetoclax. Overall survival (OS) and progression-free survival (PFS) of CLL patients are significantly improved with the use of these therapies. Adverse effects (AEs) that can occur during treatment and the presence of pre-existing comorbidities in patients can influence subsequent treatment outcomes and, consequently, OS and PFS. Managing these AEs, including cardiologic toxicity and infections (including fungal infections), as well as treating cardiovascular and other comorbidities, can be challenging due to potential drug interactions with the medications used for the management of AEs and comorbidities. Therefore, this review examined the key challenges associated with the concomitant use of novel CLL therapies and medications for managing comorbidities and AEs. This review aims to enhance and facilitate the management of patients with CLL. Copyright © 2025 Kozarac, Ivanovic, Mitrovic, Tomic Vujovic, Arsenovic, Suvajdzic-Vukovic, Bogdanovic, Vidovic, Todorovic-Balint, Bila, Mitrovic, Lekovic, Djunic, Virijevic, Trivic, Micic and Antic.

The treatment of chronic lymphocytic leukemia (CLL) consists of the continuous use of Bruton tyrosine kinase inhibitors (BTKis) such as ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib, or Bcl-2 inhibitors, such as venetoclax. Overall survival (OS) and progression-free survival (PFS) of CLL patients are significantly improved with the use of these therapies. Adverse effects (AEs) that can occur during treatment and the presence of pre-existing comorbidities in patients can influence subsequent treatment outcomes and, consequently, OS and PFS. Managing these AEs, including cardiologic toxicity and infections (including fungal infections), as well as treating cardiovascular and other comorbidities, can be challenging due to potential drug interactions with the medications used for the management of AEs and comorbidities. Therefore, this review examined the key challenges associated with the concomitant use of novel CLL therapies and medications for managing comorbidities and AEs. This review aims to enhance and facilitate the management of patients with CLL. Copyright © 2025 Kozarac, Ivanovic, Mitrovic, Tomic Vujovic, Arsenovic, Suvajdzic-Vukovic, Bogdanovic, Vidovic, Todorovic-Balint, Bila, Mitrovic, Lekovic, Djunic, Virijevic, Trivic, Micic and Antic.

The objective of this single-center study was to determine the pretreatment risk factors and influence of comorbidity on outcome in patients with acute myeloid leukemia (AML). The research involved 145 patients with AML during a 58-month follow-up period. The results suggest that the most significant predictor of poor overall survival (OS) is an adverse karyotype (P = 0.007), while for poor rate of complete remission (CR) it is age ≥55 years, and for early death the most significant predictor is comorbidity, as scored by the Hematopoetic Cell Transplantation Comorbidity Index (HCT-CI), P = 0.001. When we divided the patients into two groups: aged ≥55 years and aged <55 years, these predictors differed. In the group aged ≥55 years the most significant predictor of OS (P = 0.013) and for early death (P = 0.003) was HCT-CI (P = 0.013), while in the younger group it was karyotype (P < 0.001). The most significant predictor of CR in the elderly was increased serum lactate dehydrogenase (LDH) level (P = 0.045). In the younger patients, the most significant predictor of CR was leukocytosis (P = 0.001) and for early death it was infection as the comorbidity (P = 0.007). We point out the importance of comorbidity for OS and early death, as well as the impact of infection in patients with AML. © W.S. Maney & Son Ltd 2012.

Purpose: The aim of this 10-year retrospective study was to investigate prognostic clinical and laboratory factors significant for the outcome of patients with mucosa associated lymphoid tissue (MALT) lymphoma. Methods: The study involved 87 patients diagnosed with MALT lymphoma: 37 (42.5%) with gastrointestinal (GI) and 50 (57.5%) with non-GI localization. The following pretreatment laboratory parameters were analyzed: hempglobin, serum albumin and lactate dehydrogenase (LDH) level, beta2-microglobulin (β;2-M) and bacteriological (H.pylori) status. Estimated clinical features were: stage of disease, ECOG performance status (PS), tumor mass, number of extranodal localizations, presence of B symptomatology, splenomegaly and enlarged lymph nodes. Diagnosis of MALT lymphoma was based on histopathological analysis of tissue samples, obtained by endoscopy or surgery. Results: The median disease-free survival (DFS) was 36 months and the 5-year overall survival (OS) was 64%. OS rate of patients with non-GI localization was higher compared with patients with GI localization (p=0.001). Multivariate analysis showed hypoalbuminemia to be the most significant parameter associated with poor OS (p<0.001) for both patient groups. The most significant prognostic factor for poor OS in patients with GI localization was LDH level (p=0.031), while hypoalbuminemia was the most significant prognostic factor for poor OS in the group with non-GI disease localization (p=0.001). Conclusion: Proper therapeutic approach for MALT lymphoma patients could be planned taking into consideration poor prognostic parameters, i.e. hypoalbuminemia and elevated LDH for GI patients and hypoalbuminemia for nonGI lymphoma patients.

Purpose: The aim of this 10-year retrospective study was to investigate prognostic clinical and laboratory factors significant for the outcome of patients with mucosa associated lymphoid tissue (MALT) lymphoma. Methods: The study involved 87 patients diagnosed with MALT lymphoma: 37 (42.5%) with gastrointestinal (GI) and 50 (57.5%) with non-GI localization. The following pretreatment laboratory parameters were analyzed: hempglobin, serum albumin and lactate dehydrogenase (LDH) level, beta2-microglobulin (β;2-M) and bacteriological (H.pylori) status. Estimated clinical features were: stage of disease, ECOG performance status (PS), tumor mass, number of extranodal localizations, presence of B symptomatology, splenomegaly and enlarged lymph nodes. Diagnosis of MALT lymphoma was based on histopathological analysis of tissue samples, obtained by endoscopy or surgery. Results: The median disease-free survival (DFS) was 36 months and the 5-year overall survival (OS) was 64%. OS rate of patients with non-GI localization was higher compared with patients with GI localization (p=0.001). Multivariate analysis showed hypoalbuminemia to be the most significant parameter associated with poor OS (p<0.001) for both patient groups. The most significant prognostic factor for poor OS in patients with GI localization was LDH level (p=0.031), while hypoalbuminemia was the most significant prognostic factor for poor OS in the group with non-GI disease localization (p=0.001). Conclusion: Proper therapeutic approach for MALT lymphoma patients could be planned taking into consideration poor prognostic parameters, i.e. hypoalbuminemia and elevated LDH for GI patients and hypoalbuminemia for nonGI lymphoma patients.

Using various risk factor scores, we aimed to identify a subset of elderly patients with acute myeloid leukaemia (AML) for whom it was possible to assess the prognosis. We also aimed to develop a novel prognostic score system. This single centre study involved 102 patients of ≥60 years of age with non-promyelocytic AML. The adverse cytogenetic risk group appeared as the most significant independent prognostic factor for overall survival (OS). Our prognostic scoring system was developed after analysing prognostic risk factors and was applied for patients with favourable and intermediate (I and II) cytogenetic risk groups: age <65 years of age, normal lactate dehydrogenase (LDH) and a comorbidity score obtained applying the haematopoietic cell transplantation-specific comorbidity index (HCT-CI) < 3 = 0 points, in which age ≥65 years = 1 point and an elevated LDH score and HCT-CI ≥3 = 2 points. According to this prognostic model, patients without adverse cytogenetics were classified into three risk groups: favourable = 0-2 points, intermediate = 3-4 points and poor = > 4 points. The OS between these groups was highly significant (p < 0.001). The prognostic model developed in this study may refine the prognosis procedure of elderly AML patients without an adverse karyotype regarding OS, thereby guiding the treatment approach. © 2012 Springer Science+Business Media New York.

Using various risk factor scores, we aimed to identify a subset of elderly patients with acute myeloid leukaemia (AML) for whom it was possible to assess the prognosis. We also aimed to develop a novel prognostic score system. This single centre study involved 102 patients of ≥60 years of age with non-promyelocytic AML. The adverse cytogenetic risk group appeared as the most significant independent prognostic factor for overall survival (OS). Our prognostic scoring system was developed after analysing prognostic risk factors and was applied for patients with favourable and intermediate (I and II) cytogenetic risk groups: age <65 years of age, normal lactate dehydrogenase (LDH) and a comorbidity score obtained applying the haematopoietic cell transplantation-specific comorbidity index (HCT-CI) < 3 = 0 points, in which age ≥65 years = 1 point and an elevated LDH score and HCT-CI ≥3 = 2 points. According to this prognostic model, patients without adverse cytogenetics were classified into three risk groups: favourable = 0-2 points, intermediate = 3-4 points and poor = > 4 points. The OS between these groups was highly significant (p < 0.001). The prognostic model developed in this study may refine the prognosis procedure of elderly AML patients without an adverse karyotype regarding OS, thereby guiding the treatment approach. © 2012 Springer Science+Business Media New York.

The aims of this study were to investigate the frequency and prognostic relevance of CD56 expression in patients with acute myeloid leukemia (AML) and to compare the importance of CD56 expression with standard prognostic factors, such as age, leukocytosis, cytogenetic abnormalities and performance status. We analyzed the data of 184 newly diagnosed patients with non-promyelocytic AML and a follow-up of 36 months. The median patient age was 58 years, with a range of 18-79. CD56+ antigen was recorded in 40 patients (21.7%). CD56 + was the most significant risk factor for OS: P = 0.05. The most significant factor for a poor rate of CR was age ≥ 55 years (P = 0.001). CD56 positivity had no significant influence on CR rate, but it was the most significant risk factor for disease-free survival (P = 0.005). The CD56 antigen is an independent prognostic risk factor, and its presence should be measured regularly for a better prognostic assessment of patients with AML. Copyright © Springer Science+Business Media, LLC 2011.

The aims of this study were to investigate the frequency and prognostic relevance of CD56 expression in patients with acute myeloid leukemia (AML) and to compare the importance of CD56 expression with standard prognostic factors, such as age, leukocytosis, cytogenetic abnormalities and performance status. We analyzed the data of 184 newly diagnosed patients with non-promyelocytic AML and a follow-up of 36 months. The median patient age was 58 years, with a range of 18-79. CD56+ antigen was recorded in 40 patients (21.7%). CD56 + was the most significant risk factor for OS: P = 0.05. The most significant factor for a poor rate of CR was age ≥ 55 years (P = 0.001). CD56 positivity had no significant influence on CR rate, but it was the most significant risk factor for disease-free survival (P = 0.005). The CD56 antigen is an independent prognostic risk factor, and its presence should be measured regularly for a better prognostic assessment of patients with AML. Copyright © Springer Science+Business Media, LLC 2011.

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC), leading to potentially life-threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem. Objective: The objective of our study was to identify the incidence and predictive value of demographic data, clinical–laboratory parameters, and thrombosis risk assessment models (RAMs) for venous thromboembolism (VTE) in patients with APL. Methods: This study was a retrospective study conducted on adult patients with APL who were treated between 2006 and 2024 at the Clinic of Hematology UCCS with all-trans retinoic acid (ATRA) and anthracycline. The demographic and clinical–laboratory data related to VTE were collected and analyzed alongside the predictive value of two RAMs proposed by Al-Ani and Paterno and colleagues. Results: Among the one-hundred-fifty-five adult patients with APL, VTE was diagnosed in twenty-eight cases (18.1%). The most common location for thrombosis was in the central venous catheter (CVC), which affected twelve (42.8%) patients. A total of six (21.4%) patients had deep vein thrombosis (DVT), one patient (3.6%) showed a pulmonary embolism (PE), and thrombosis at unusual sites was present in nine (32.1%) patients. Our analyses showed that neither Al-Ani’s RAM nor the RAM proposed by Paterno and colleagues were predictive for VTE in patients with APL. The C statistics value for the Al-Ani model was ROC = 0.514, and, for Paterno’s RAM, it was ROC = 0.521. The independent risk factors for VTE, identified via multivariate analysis, were CD114 expression (p = 0.005, OR = 6.4 IC 95%: [1.8–23.2]) and the absence of bleeding at presentation (p = 0.013, OR = 0.086 IC 95%: [0.01–0.59]). Conclusions: To the best of our knowledge, this is the first study showing that a higher expression of CD114 increases the risk of VTE. The absence of bleeding at presentation in patients with APL correlates with thrombosis. Further analyses are needed to confirm these findings and help to develop therapeutic strategies to prevent VTE complications. So far, no risk assessment model has been sufficient to stratify patients with APL according to their risk of VTE. © 2024 by the authors.

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC), leading to potentially life-threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem. Objective: The objective of our study was to identify the incidence and predictive value of demographic data, clinical–laboratory parameters, and thrombosis risk assessment models (RAMs) for venous thromboembolism (VTE) in patients with APL. Methods: This study was a retrospective study conducted on adult patients with APL who were treated between 2006 and 2024 at the Clinic of Hematology UCCS with all-trans retinoic acid (ATRA) and anthracycline. The demographic and clinical–laboratory data related to VTE were collected and analyzed alongside the predictive value of two RAMs proposed by Al-Ani and Paterno and colleagues. Results: Among the one-hundred-fifty-five adult patients with APL, VTE was diagnosed in twenty-eight cases (18.1%). The most common location for thrombosis was in the central venous catheter (CVC), which affected twelve (42.8%) patients. A total of six (21.4%) patients had deep vein thrombosis (DVT), one patient (3.6%) showed a pulmonary embolism (PE), and thrombosis at unusual sites was present in nine (32.1%) patients. Our analyses showed that neither Al-Ani’s RAM nor the RAM proposed by Paterno and colleagues were predictive for VTE in patients with APL. The C statistics value for the Al-Ani model was ROC = 0.514, and, for Paterno’s RAM, it was ROC = 0.521. The independent risk factors for VTE, identified via multivariate analysis, were CD114 expression (p = 0.005, OR = 6.4 IC 95%: [1.8–23.2]) and the absence of bleeding at presentation (p = 0.013, OR = 0.086 IC 95%: [0.01–0.59]). Conclusions: To the best of our knowledge, this is the first study showing that a higher expression of CD114 increases the risk of VTE. The absence of bleeding at presentation in patients with APL correlates with thrombosis. Further analyses are needed to confirm these findings and help to develop therapeutic strategies to prevent VTE complications. So far, no risk assessment model has been sufficient to stratify patients with APL according to their risk of VTE. © 2024 by the authors.

Background. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods. In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results. IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions. Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection. © 2016 Radiol Oncol.

One of the risk factors for vascular obstetric complications, such as intrauterine growth restriction (IUGR), is inherited thrombophilias. Nevertheless, routine screening for thrombophilias is not endorsed in pregnant women due to their low prevalence and conflicting results of published studies regarding the usefulness of screening in these patients. The cause of IUGR remains unknown in almost 1 quarter of cases. There are no published studies evaluating the association of inherited thrombophilias and IUGR in patients with IUGR of unknown origin. Understanding and preventing IUGR is an important public health concern, as IUGR has been associated with fetal mortality and neonatal morbidity, as well as adverse long-standing consequences. This study aimed to evaluate the prevalence of inherited thrombophilias in IUGR of unknown cause and to test the association between the inherited thrombophilias and IUGR of unknown cause. This study included 33 cases of IUGR of unknown cause tested for inherited thrombophilias and 66 controls individually matched for age, ethnicity, and smoking status. Patients with plasminogen activator inhibitor 1 (PAI-1) and methylenetetrahydrofolate reductase (MTHFR) had significantly higher odds for IUGR of unknown cause (P < .001 and P = .002, respectively) with OR 13.546 (CI 95% 3.79–48.37) and 8.139 (CI 95% 2.20–30.10), respectively. A positive association between other inherited thrombophilias (homozygous 20210 prothrombin gene mutation and homozygous factor V Leiden) and IUGR of unknown cause was also found, P = .096, OR 6.106 (CI 95% 0.72–51.30), although it was not statistically significant (P = .096, OR = 6.106, CI 95% 0.72–51.30). Our results indicate that PAI-1 and MTHFR thrombophilias represent risk factors for IUGR of otherwise unidentified cause. Copyright © 2018 the Author(s).

Background: Some patients with paraproteinemia have platelet aggregation disorders and the aim of this study was to examine disturbance of platelet aggregation in healthy blood donors by isolated paraprotein in vitro. Methods: Using Rivanol, paraprotein was separated from the serum of ten patients with paraproteinemia, who had decreased platelet aggregation with several inducers. Platelet aggregation in ten healthy donors was measured with and without addition of the isolated induced paraprotein. The test was repeated with added human immunoglobulins for intravenous use. Results: Average of maximal levels of platelet aggregation has been significantly decreased in plasma rich in platelets (PRP) of healthy donors after addition of paraprotein when inducers are used: adenosine diphosphate (ADP) (P = 0.007), collagen (COL) (P = 0.008), ristocetin (RIS) (P = 0.001), and epinephrine (EPI) (P = 0.002). Average of latent time of platelet aggregation was significantly prolonged in healthy donors after addition of paraprotein with inducers: COL (P = 0.008), RIS (P = 0.008) and EPI (P = 0.006) while addition of human immunoglobulins caused no change in platelet aggregation. In comparison, when human immunoglobulins were added, maximal platelet aggregation and latent time did not change significantly. Paraprotein isolated from patients with paraproteinamia, who had decrease platelet aggregation, had significantly decreased platelet aggregation when added to PRP of healthy donors, in vitro. Conclusion: Platelet aggregation was not significantly changed was confirmed with addition of human immunoglobulins. © 2014 Wiley Periodicals, Inc.

Background: Some patients with paraproteinemia have platelet aggregation disorders and the aim of this study was to examine disturbance of platelet aggregation in healthy blood donors by isolated paraprotein in vitro. Methods: Using Rivanol, paraprotein was separated from the serum of ten patients with paraproteinemia, who had decreased platelet aggregation with several inducers. Platelet aggregation in ten healthy donors was measured with and without addition of the isolated induced paraprotein. The test was repeated with added human immunoglobulins for intravenous use. Results: Average of maximal levels of platelet aggregation has been significantly decreased in plasma rich in platelets (PRP) of healthy donors after addition of paraprotein when inducers are used: adenosine diphosphate (ADP) (P = 0.007), collagen (COL) (P = 0.008), ristocetin (RIS) (P = 0.001), and epinephrine (EPI) (P = 0.002). Average of latent time of platelet aggregation was significantly prolonged in healthy donors after addition of paraprotein with inducers: COL (P = 0.008), RIS (P = 0.008) and EPI (P = 0.006) while addition of human immunoglobulins caused no change in platelet aggregation. In comparison, when human immunoglobulins were added, maximal platelet aggregation and latent time did not change significantly. Paraprotein isolated from patients with paraproteinamia, who had decrease platelet aggregation, had significantly decreased platelet aggregation when added to PRP of healthy donors, in vitro. Conclusion: Platelet aggregation was not significantly changed was confirmed with addition of human immunoglobulins. © 2014 Wiley Periodicals, Inc.

Introduction Thrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to10-15%. Materials and Methods We retrospectively analyzed the data on TE appearance in 63 APL patients. Results TE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20 months vs 6 during 76 months, P = 0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P = 0.046), PT (P = 0.022), aPTT (P = 0.044), ISTH DIC score (P = 0.001), bcr3 (P = 0.02) and FLT3-ITD (P = 0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P = 0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P = 0.05). Regarding risk factors for arterial TE we failed to identify any. Conclusions We have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score < 5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G. © 2014 Elsevier Ltd.