Papers by Evgueniy Hadjiev
Hepcidin is a 25 - amino peptide hormone that regulates iron homeostasis. Its serum quantificatio... more Hepcidin is a 25 - amino peptide hormone that regulates iron homeostasis. Its serum quantification helps to provide the right therapeutic choice in iron - deficiency anemia and anemia in chronic diseases. We determined serum hepcidin levels using ELISA assay i n 125 patients with chronic kidney diseases (CKD) [stages from II to V] (n=60), r heumatoid arthritis (n=30), β - talasemia major (n=15) and iron - deficiency anemia (IDA; n=20) for a period 2012 – 2014 year. We compare their results to control group. The refer ence ranges for serum hepcidin in Bulgarian population are 3.052 - 37.750 µg/L. We found statistically significant differences in serum hepcidin levels between measured groups : CKD stages II to IV – 89.9 ± 9.2 μg/L; CKD stage V – 321.4 ± 20.5 μg/L ; β - talas emia major – 0.78 ± 0.9 μg/L ; ; IDA – 1.14 ± 1.2 μg/L; RA – 27.9 ± 8.7 μg/L; P < 0.001. Our results may support the right choice of a therapeutic approach to the anemia in patients with different disorders of ...
Chronic myeloid leukemia (CML) is characterized with clonal proliferation of pluripotent bone mar... more Chronic myeloid leukemia (CML) is characterized with clonal proliferation of pluripotent bone marrow stem sells and the fusion Bcr-Abl gene with increased tyrosine kinase activity. The main pathogenetic mechanisms are associated with impaired cell adhesion, deregulation of cell growth and resistance to normal mechanisms of programmed cell death (apoptosis). The mechanisms that lead to the evolution of the disease and transformation into blast crisis are still insuffi ciently studied. A search is directed to genes that are associated with cell cycle control, differentiation and apoptosis and which are being affected in other malignant neoplasms. The aim of the review is to summarize the molecular-cytogenetic abnormalities in the evolution of CML, including the loss of tumor suppressor functions ((р53, RB1, АТМ, CDKN2), activation of oncogenes other than Bcr-Abl (MYC, Jak2) and telomere shortening. Some evidence that progression is probably related to a wide range of alternating DNA d...
American Journal of Hematology
Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher dis... more Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat‐treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9‐month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open‐label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3–6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n = 13), mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n = 13), mean hemoglobin increased 1.4 g/dl (from 11.9 to 13.4 g/dl, n = 12), mean platelet count increased by 87% (from 67.6 to 122.6 × 109/L, n = 12), median chitotriosidase decreased by 82% (from 13 394 to 2312 nmol/h/ml, n = 11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/ml, n = 11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/ml, n = 10), and mean spine T‐score increased from −1.07 (osteopenia) to −0.53 (normal) (n = 9). The magnitude of improvement in Gaucher disease manifestations and biomarkers over time was similar among the full trial cohort. Eliglustat was well‐tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment.
Journal of IMAB - Annual Proceeding (Scientific Papers), May 17, 2018
Mikulicz's syndrome is a chronic swelling of the lacrimal and major salivary glands usually assoc... more Mikulicz's syndrome is a chronic swelling of the lacrimal and major salivary glands usually associated with significantly decreased or lack of lacrimation and xerostomia, accompanied by lymphocytic infiltration. It is associated with other entities like tuberculosis, lupus erythematosus, lymphoma, leukemia, etc. A case of 70 years old man with painless, dense swelling of the left parotid gland and medical history of leukemia is presented. The decreased secretory activity of the parotid gland is observed. The patient is referred for laboratory blood test and ultrasound examination of the parotid glands. Mikulicz's syndrome associated with acute myelogenous leukemia was identified. Laboratory blood test reveals leukocytosis (118 g/L). The progress of the glands pathology seems to be associated with the severity of the main disease and appears to be a poor prognostic sign. Based on the findings the definitive diagnosis in the reported case is Mikulicz's syndrome associated with leukemia. The swelling is expected to disappear spontaneously or after treatment with corticosteroids. However, paliative treatment was conducted due to the severity of the systemic disease.
American journal of hematology, 2017
Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gauche... more Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in i...
Acta Medica Bulgarica
Address for correspondence: Dr Milena Velizarova, PhD Department of Clinical Laboratory and Clini... more Address for correspondence: Dr Milena Velizarova, PhD Department of Clinical Laboratory and Clinical Immunology; University Alexander’s Hospital; 1 G. Sofiiski str.; 1431 Sofia, Bulgaria; tel. +359 2 92 30 916 ; e-mail: [email protected]
Leukemia & Lymphoma, 2021
Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory c... more Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE II trial, Leukemia & Lymphoma,
Molecular Genetics and Metabolism
Blood Cells, Molecules, and Diseases
Blood cells, molecules & diseases, 2018
Pathology oncology research : POR, Jan 14, 2017
Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Phil... more Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutatio...
Molecular Genetics and Metabolism, 2017
Turkish journal of haematology : official journal of Turkish Society of Haematology, Jan 5, 2008
The majority of adults diagnosed with acute myeloid leukemia (AML) display acquired cytogenetic a... more The majority of adults diagnosed with acute myeloid leukemia (AML) display acquired cytogenetic aberrations at presentation. In this article, we present the major cytogenetic findings regarding AML and review their clinical significance for achievement of the first complete remission. We studied 71 adult patients with de novo AML, without previous myelodysplasia or alkylating therapy. Conventional cytogenetics and FISH were performed on bone marrow cells. The patients with AML were assigned to 12 subgroups according to established data for cytogenetic, molecular and general laboratory results. The selection of the analyzed parameters is consistent with internationally accepted "prognostic factors" in adult AML. Complete remission upon induction therapy was achieved in 40% of cases (in a mean period of 2.3 months from therapy initiation). The patients with t(15;17) PML-RARA and inv(16)/CBFbeta-MYH11ë demonstrated the highest frequency of complete remission. Patients with hy...
JAMA, 2015
IMPORTANCE Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopeni... more IMPORTANCE Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed. OBJECTIVE To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. Of 72 patients screened, 40 were enrolled. INTERVENTIONS Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg twice daily; n = 20) or placebo (n = 20) for 9 months. MAIN OUTCOMES AND MEASURES The primary efficacy end point was percentage change in spleen volume in multiples of normal from baseline to 9 months; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count. RESULTS All patients had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild or moderate hepatomegaly, and 20% had mild anemia. Least-square mean spleen volume decreased by 27.77% (95% CI, −32.57% to −22.97%) in the eliglustat group (from 13.89 to 10.17 multiples of normal) vs an increase of 2.26% (95% CI, −2.54% to 7.06%) in the placebo group (from 12.50 to 12.84 multiples of normal) for an absolute treatment difference of −30.03% (95% CI, −36.82% to −23.24%; P < .001). For the secondary end points, the least-square mean absolute differences between groups all favored eliglustat, with a 1.22-g/dL increase in hemoglobin level (95% CI, 0.57-1.88 g/dL; P < .001), 6.64% decrease in liver volume (95% CI, −11.37% to −1.91%; P = .007), and 41.06% increase in platelet count (95% CI, 23.95%-58.17%; P < .001). No serious adverse events occurred. One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study. CONCLUSIONS AND RELEVANCE Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. The clinical significance of these findings is uncertain, and more definitive conclusions about clinical efficacy and utility will require comparison with the standard treatment of enzyme replacement therapy as well as longer-term follow-up.
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Papers by Evgueniy Hadjiev