Browsing by Author "Antic, Darko (23979576100)"

Based on the results of clinical trials, there is no global consensus on the optimal first-line therapy for patients with advanced Hodgkin lymphoma (HL) with both ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow-up for all patients was 91 months; the estimated 5-yr event-free survival was 62% and the 5-yr overall survival (OS) 76%. Multivariate Cox regression analysis revealed that patients with IPS ≥ 3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial. © 2014 John Wiley & Sons A/S.

Introduction: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. Materials and Methods: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. Results: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). Conclusion: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED. © The Author(s) 2022.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Background: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. Aim: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. Results: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23–6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581–63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329–13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212–23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948–21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092–5.007). Conclusions: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30. © 2023 by the authors.

Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients. © 2019, Arányi Lajos Foundation.

Fludarabine plus cyclophosphamide (FC) chemotherapy is the basis of treatment protocols used in management of chronic lymphocytic leukemia (CLL). In some patients, response to therapy may be affected by aberrant function of genes involved in pharmacokinetics and pharmacodynamics of the drugs. The aim of this research was to assess the impact of pharmacogenetic variability, namely expression of SLC28A3 gene and the presence of CYP2B6*6 variant allele, on the FC treatment efficacy. Forty-four CLL patients with functional TP53 gene at the time of FC initiation were enrolled in this study. CYP2B6 genotyping was performed by polymerase chain reaction and direct sequencing. SLC28A3 expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Significantly higher pretreatment levels of SLC28A3 mRNA were detected in patients who failed to respond to FC in comparison to patients who achieved complete and partial response (p = 0.01). SLC28A3 high-expressing cases were almost ten times more likely not to respond to FC than low-expressing cases (OR = 9.8; p = 0.046). However, association of SLC28A3 expression with progression-free survival (PFS) and overall survival (OS) was not observed. CYP2B6*6 allele, detected in 24 patients (54.6%), exerted no association with the attainment of response to FC, as well as with PFS and OS. The results of this study demonstrate that SLC28A3 expression is a significant predictor of FC efficacy in CLL patients with intact TP53. Elevated SLC28A3 mRNA levels are associated with inferior short-term response to FC, suggesting that, if validated on larger cohorts, SLC28A3 expression may become a biomarker useful for pretreatment stratification of patients. © 2019, Arányi Lajos Foundation.

Purpose: Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI). Methods: The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method. Results: The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases. Conclusion: IPI is an independent prognosticator for DLBCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6- DLBCL benefited from R-CHOP.

Purpose: Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI). Methods: The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method. Results: The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases. Conclusion: IPI is an independent prognosticator for DLBCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6- DLBCL benefited from R-CHOP.

[No abstract available]

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34-expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. © 2017 AACR.

We present the case of a 69-year-old Caucasian man with a 5-year history of untreated chronic lymphocytic leukemia who presented with Merkel cell carcinoma on the right gluteal region. Six months after surgical treatment of Merkel cell carcinoma, we detected massive lymphadenopathy in the right retroperitoneum descending to the inguinum. A lymph node biopsy confirmed Merkel cell carcinoma relapse, and the patient was unsuccessfully treated with radiotherapy. As patients with chronic lymphocytic leukemia have a risk for developing a secondary malignancy, skin lesions need to be carefully examined and new lymphadenopathy must be pathohistologically evaluated. © 2015, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated. © 2021, The Author(s).

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated. © 2021, The Author(s).

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provide evidence-based recommendations to policy-makers to assist them in making informed immunization policy and programme decisions. During the COVID-19 pandemic, NITAGs faced many challenges in making evidence-based recommendations for COVID-19 vaccines due to the rapidly evolving situation with new vaccine products available in a short time period and limited data on vaccine effectiveness. The authors reviewed the process used by Serbia's NITAG, which is called the Serbian Expert Committee on Immunization, to develop COVID-19 vaccine recommendations during the pandemic. The article examines the challenges and successes faced by the committee. Serbia's expert committee used the best available evidence to develop over forty recommendations on all aspects of COVID-19 vaccination. These expert committee recommendations facilitated the early procurement and successful roll-out of COVID-19 vaccines, guidance for vaccination of individuals at the highest risk, and high COVID-19 vaccination coverage in the country. The availability of five COVID-19 vaccines in Serbia was an advantage for the successful roll-out but posed challenges for the expert committee. Serbia's expert committee plans to use the experience and best practices developed during the pandemic to improve and expand its work moving forward. Copyright © 2022 Markovic-Denic, Popadic, Jovanovic, Bonaci-Nikolic, Samardzic, Tomic Spiric, Rancic, Sankar Datta, Mosina, Jancic, Vukomanovic, Jovanovic, Vukomanovic, Antic, Veljkovic, Saponjic and Jacques-Carroll.

Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty-five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m2, reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0-1), intermediate (score 2-3), and high (score >3). For patients classified at risk (intermediate and high-risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high-risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma – ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014–1019, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22–69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk. © 2024 by the authors.

Introduction: The B-cell lymphoma/leukaemia 11A (BCL11A) gene encodes a Krüppel-like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B-cell malignancies, particularly CLL. Methods: The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly-diagnosed CLL patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and association with clinical and molecular variables was assessed. Results: BCL11A was significantly overexpressed in CLL samples compared to control samples (p < 0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum β2-microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase (p = 0.031), Binet A stage (p = 0.047) and mutated IGHV (p = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p < 0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high- versus BCL11A low-expressing cases was detected (21 vs. 6 months; p = 0.164). Conclusion: The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance. © 2022 John Wiley & Sons Ltd.

Introduction: The B-cell lymphoma/leukaemia 11A (BCL11A) gene encodes a Krüppel-like transcription factor involved in lymphocyte development during normal haematopoiesis. Aberrant expression of BCL11A has been observed in several haematological malignancies, including chronic lymphocytic leukaemia (CLL). However, its functions in the regulatory networks of malignant B lymphocytes are poorly understood, as are the relations to clinical course and outcome of B-cell malignancies, particularly CLL. Methods: The expression of BCL11A was analysed in peripheral blood mononuclear cells of 87 newly-diagnosed CLL patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), and association with clinical and molecular variables was assessed. Results: BCL11A was significantly overexpressed in CLL samples compared to control samples (p < 0.001). BCL11A expression level exhibited no association with age, sex, leukocyte, lymphocyte and platelet counts, haemoglobin level, serum β2-microglobulin, CD38 status and cytogenetic abnormalities. On the other hand, high BCL11A expression was associated with low serum lactate dehydrogenase (p = 0.031), Binet A stage (p = 0.047) and mutated IGHV (p = 0.028). In addition, a positive correlation with BCL2/BAX mRNA ratio was observed (r = 0.36; p < 0.001). Regarding the association with the time to first treatment (TTFT), a trend towards longer median TTFT in BCL11A high- versus BCL11A low-expressing cases was detected (21 vs. 6 months; p = 0.164). Conclusion: The results of this study show that BCL11A is upregulated in CLL patients, and that high BCL11A expression at diagnosis may be associated with better prognosis. These data are consistent with the role of BCL11A expression in CLL biology, and imply its potential prognostic relevance. © 2022 John Wiley & Sons Ltd.

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient’s clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma. © 2016, The Japanese Society of Hematology.

There is a paucity of data on the effects of enzyme replacement therapy (ERT) on the coagulation abnormalities and platelet function of patients with Gaucher's disease (GDPs) and much of this data are controversial. This study investigates the haemostatic parameters in treatment-nave GDPs and the effects of ERT. 31 Serbian treatment-nave type 1 GDPs (M/F 17/14; median age 49 years, splenectomized 9/31) were studied. The complete blood count, prothrombin time (PT), activated partial tromboplastin time (aPTT) and coagulation factors were measured using the standard methods. Platelet aggregation was assessed with a whole-blood aggregometer. Splenic volumes were assessed using computer tomography. Twenty-one patients were treated with ERT (Imiglucerase). The haemostatic parameters were assessed after 6, 12 and 24 months (ERT 6, 12, 24). Initially bleeding episodes were registered in 10/31 GDPs. Median platelet count was 108×10 9/L; 22/31 GDPs were thrombocytopenic. The PT and aPTT values were abnormal in 16/31 and 13/31 GDPs, respectively. Platelet aggregation abnormalities were recorded in 19/31GDPs. Median platelet aggregation was reduced in response to adenosine-diphosphate 5mol/L (ADP 5 0.46) and collagen 5mol/L (Col5 0.47). Splenic volume inversely correlated with the platelet count and a reduced response to arachidonic acid (AA), Col5 and ADP5 (p<0.05). The splenectomized GDPs had a significantly lower platelet aggregation to Col 10 (p<0.05). Bleeding GDPs had a significantly lower platelet count, higher chitotriosidase levels and a greater splenic volume compared to non-bleeding patients (p<0.01). ERT: The number of bleeding GDPs had significantly decreased by ERT 6 (1/10; p<0.01). The platelet count had significantly increased by ERT 6 (ERT 6 180×10 9/L, p<0.01). The PT increased significantly from ERT0 to ERT 24 (PT0 65%, PT 24 81%; p<0.05). The von Willebrand factor had increased significantly by ERT 6 and ERT 24 (ERT0 56%, ERT 6 70%, ERT 12 70%, ERT 24 86%; p<0.01). The number of GDPs with abnormal platelet aggregation had decreased significantly by ERT 6 (10/19; p<0.05). Platelet aggregation on ADP 10 and AA significantly increased by ERT 6 (ADP 10: ERT 0 0.75, ERT 6 0.8 p<0.01; AA: ERT0 0.7, ERT 6 0.8 p<0.05). In conclusion, platelet dysfunction and coagulation abnormalities were found in a considerable number of our GDPs. The absence of severe bleeding episodes suggests that the haemostatic system is sufficiently balanced and therefore the exact mechanism of the etiology of these abnormalities need to be fully clarified. ERT resulted in the cessation of bleeding and marked increase in platelet count, PT, vWF and platelet aggregation. © 2012 Informa UK Ltd. All rights reserved.