Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory p... more Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029)....
Serbian Journal of Experimental and Clinical Research, 2022
Chronic granulocytic leukemia (CGL), Ph + is a chronic myeloproliferative disorder, which, due to... more Chronic granulocytic leukemia (CGL), Ph + is a chronic myeloproliferative disorder, which, due to its specificity for many decades, has attracted the attention of researchers of specialties. This disease was among the first malignant haemopathies that received their “ID card” since molecular precisely defined the basic pathological substrate, that origin of the disease. Over the past decades we have witnessed the evolution of the therapeutic approach in the treatment of from oral cystostatic therapy, radiotherapy, through recombinant interferon alpha (IFN-alpha), haematopoeza stem cell transplantation, to the targeted molecular therapy of the tyrosine inhibitor (TKI). In this report we present patient with a diagnosis of Ph + in the early chronic phase at the age of 13 all relevant analyzes. During the past 26 years, all modalities of CGL treatment were applied in patients, according to the time period, concluding with the second generation resulting in complete remission of disease...
Purpose: The aim of this study was to analyze the occurrence of the most frequent BCR-ABL transcr... more Purpose: The aim of this study was to analyze the occurrence of the most frequent BCR-ABL transcript variants (b3a2, b2a2 and e1a2) in Serbian patients with chronic myeloid leukemia (CML) and compare it with the occurrence reported in other populations. Methods: We analyzed peripheral blood and bone marrow samples of 136 Serbian patients with CML by RT-PCR and cytogenetic methods. Results: In 100 patients (73.5%) the b3a2 and in 34 (25%) the b2a2 forms of BCR-ABL were detected. One (0.75%) patient was BCR-ABL negative, but in lymphoblastic transformation he expressed the e1a2 [corrected] transcript of BCR-ABL. One (0.75%) patient displayed both b2a2 and b3a2 forms of BCR-ABL. Analysis of this group according to karyotype showed b3a2 predominance (79%) in patients with classic t(9;22); b2a2 was found in 20% and both b2a2 and b3a2 forms in 1%. In variant translocations b3a2 in 65% and b2a2 in 35% of the patients were detected. In contrast, the subgroup with normal karyotype expressed slight predominance of the b2a2 form (50%); b3a2 was found in 43% of the patients and one patient (7%) displayed e1a2. Conclusion: Predominance of the b3a2 form in Serbian patients with CML is in concordance with other relevant investigations, conducted mostly on Caucasian ethnic groups, but in contrast to the study performed on the Mestizo ethnic group in Ecuador. Slight predominance of the b2a2 form was also noticed among the patients with normal karyotype.
Between January 1986 and July 1990, 17 patients with acquired aplastic anemia were treated with A... more Between January 1986 and July 1990, 17 patients with acquired aplastic anemia were treated with ALG or ATG combined with high doses of methylprednisolone. The mean age was 24.3 years (from 4 to 51 years). There were 9 cases with idiopathic etiology of acquired aplastic anemia; in 7 cases aplastic anemia was developed during or after HBsAg infection. In one case aplastic anemia was developed during tuberculous kidney infection. The remission of the disease was achieved in 11 of 17 cases (complete remission in 9-53%, and partial in 2-12% patients). Six (35%) patients did not respond to the treatment with ALG. One patient died of infection and hemorrhagic complications, two weeks after the therapy, without responding to the treatment with ALG. The four year survival rate without recidives was 65% (11/17). Four (23.5%) patients developed clonal diseases: PNH in 2; MDS in 1 and AL in 1 patient, 24, 38, 9 and 6 months after the therapy with ALG, respectively. The age of the patients is a valuable prognostic parameter (all patients under 20 years of age entered the remission), which cannot be said for pretreatment levels of reticulocytes, neutrophils and platelets. In none of the patients adverse effects of ALG were observed. The treatment was conducted in isolated rooms with sterile air circulation. ALG combined with high doses of methylprednisolone, for the majority of patients with aplastic anemia represents a drug of choice and is an appropriate alternative therapy to alogenic bone marrow transplantation, especially for patients with no HLA identical bone marrow donor.
Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after b... more Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after bone marrow transplantation. We report the case of 14-year-old boy who relapsed 34 months after sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukemia. Subsequently, he received three infusions of donor mononuclear cells (DMNC) harvested in steady state hematopoiesis and one G-CSF mobilized-peripheral blood mononuclear cells (PBMC) infusion. Simultaneously, test named as--"Test of Mixed Progenitors" (TMP) was performed for the assessment whether the outcome of donor leukocyte infusion treatment could be predicted. Prior to DMNC infusions, the CFU-GM and BFU-E colony assays were performed for donor's and recipient's PBMC individually, as well as for the mixture of these cells at 1:1 ratio. The cells were plated either directly in the semisolid medium or after 24 h preincubation treatment. Significantly lower values for CFU-GM derived colonies were determined in TMP in comparison to the CFU-GM values obtained for the recipient's cells. The reduced number of CFU-GM was determined both in TMP performed without preincubation treatment, app. 80% and after the 24 h preincubation, app. 55%. The reduced number of BFU-E derived colonies (app. 44%) was observed only related to recipient's cells and after the preincubation treatment of the cells. The patient did not develop GVHD and currently (40 months after the first infusion). He remained well in complete hematological, cytogenetic, molecular and clinical remission, which was the most direct evidence of the GVL effect. The novel in vitro TMP test in which the specific contribution of donor's leukocytes to the growth of recipient's hematopoietic precursor cell growth was determined, correlated with the clinical outcome.
Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics a... more Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: <2006 n=389 (9.4%), 2006-2010 n=910 (22%), 2011-2014 n=1148 (27.7%) and 2015-2018 n=1695 (40.9%). A steady increase in MF allo-HCT activity over time was apparent paralleled with increasing numbers of participating transplant centres. A total of 2603 (62.8%) patients were male, 3239 (78.2%) had Primary MF, 409 (9.9%) and 494 (11.9%) post-Polycythaemia Vera and post-Essential Thrombocythaemia MF, respectively. An increased median interval (lnterquartile range (IQR)) between diagnosis ...
Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory p... more Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029)....
Serbian Journal of Experimental and Clinical Research, 2022
Chronic granulocytic leukemia (CGL), Ph + is a chronic myeloproliferative disorder, which, due to... more Chronic granulocytic leukemia (CGL), Ph + is a chronic myeloproliferative disorder, which, due to its specificity for many decades, has attracted the attention of researchers of specialties. This disease was among the first malignant haemopathies that received their “ID card” since molecular precisely defined the basic pathological substrate, that origin of the disease. Over the past decades we have witnessed the evolution of the therapeutic approach in the treatment of from oral cystostatic therapy, radiotherapy, through recombinant interferon alpha (IFN-alpha), haematopoeza stem cell transplantation, to the targeted molecular therapy of the tyrosine inhibitor (TKI). In this report we present patient with a diagnosis of Ph + in the early chronic phase at the age of 13 all relevant analyzes. During the past 26 years, all modalities of CGL treatment were applied in patients, according to the time period, concluding with the second generation resulting in complete remission of disease...
Purpose: The aim of this study was to analyze the occurrence of the most frequent BCR-ABL transcr... more Purpose: The aim of this study was to analyze the occurrence of the most frequent BCR-ABL transcript variants (b3a2, b2a2 and e1a2) in Serbian patients with chronic myeloid leukemia (CML) and compare it with the occurrence reported in other populations. Methods: We analyzed peripheral blood and bone marrow samples of 136 Serbian patients with CML by RT-PCR and cytogenetic methods. Results: In 100 patients (73.5%) the b3a2 and in 34 (25%) the b2a2 forms of BCR-ABL were detected. One (0.75%) patient was BCR-ABL negative, but in lymphoblastic transformation he expressed the e1a2 [corrected] transcript of BCR-ABL. One (0.75%) patient displayed both b2a2 and b3a2 forms of BCR-ABL. Analysis of this group according to karyotype showed b3a2 predominance (79%) in patients with classic t(9;22); b2a2 was found in 20% and both b2a2 and b3a2 forms in 1%. In variant translocations b3a2 in 65% and b2a2 in 35% of the patients were detected. In contrast, the subgroup with normal karyotype expressed slight predominance of the b2a2 form (50%); b3a2 was found in 43% of the patients and one patient (7%) displayed e1a2. Conclusion: Predominance of the b3a2 form in Serbian patients with CML is in concordance with other relevant investigations, conducted mostly on Caucasian ethnic groups, but in contrast to the study performed on the Mestizo ethnic group in Ecuador. Slight predominance of the b2a2 form was also noticed among the patients with normal karyotype.
Between January 1986 and July 1990, 17 patients with acquired aplastic anemia were treated with A... more Between January 1986 and July 1990, 17 patients with acquired aplastic anemia were treated with ALG or ATG combined with high doses of methylprednisolone. The mean age was 24.3 years (from 4 to 51 years). There were 9 cases with idiopathic etiology of acquired aplastic anemia; in 7 cases aplastic anemia was developed during or after HBsAg infection. In one case aplastic anemia was developed during tuberculous kidney infection. The remission of the disease was achieved in 11 of 17 cases (complete remission in 9-53%, and partial in 2-12% patients). Six (35%) patients did not respond to the treatment with ALG. One patient died of infection and hemorrhagic complications, two weeks after the therapy, without responding to the treatment with ALG. The four year survival rate without recidives was 65% (11/17). Four (23.5%) patients developed clonal diseases: PNH in 2; MDS in 1 and AL in 1 patient, 24, 38, 9 and 6 months after the therapy with ALG, respectively. The age of the patients is a valuable prognostic parameter (all patients under 20 years of age entered the remission), which cannot be said for pretreatment levels of reticulocytes, neutrophils and platelets. In none of the patients adverse effects of ALG were observed. The treatment was conducted in isolated rooms with sterile air circulation. ALG combined with high doses of methylprednisolone, for the majority of patients with aplastic anemia represents a drug of choice and is an appropriate alternative therapy to alogenic bone marrow transplantation, especially for patients with no HLA identical bone marrow donor.
Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after b... more Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after bone marrow transplantation. We report the case of 14-year-old boy who relapsed 34 months after sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukemia. Subsequently, he received three infusions of donor mononuclear cells (DMNC) harvested in steady state hematopoiesis and one G-CSF mobilized-peripheral blood mononuclear cells (PBMC) infusion. Simultaneously, test named as--"Test of Mixed Progenitors" (TMP) was performed for the assessment whether the outcome of donor leukocyte infusion treatment could be predicted. Prior to DMNC infusions, the CFU-GM and BFU-E colony assays were performed for donor's and recipient's PBMC individually, as well as for the mixture of these cells at 1:1 ratio. The cells were plated either directly in the semisolid medium or after 24 h preincubation treatment. Significantly lower values for CFU-GM derived colonies were determined in TMP in comparison to the CFU-GM values obtained for the recipient's cells. The reduced number of CFU-GM was determined both in TMP performed without preincubation treatment, app. 80% and after the 24 h preincubation, app. 55%. The reduced number of BFU-E derived colonies (app. 44%) was observed only related to recipient's cells and after the preincubation treatment of the cells. The patient did not develop GVHD and currently (40 months after the first infusion). He remained well in complete hematological, cytogenetic, molecular and clinical remission, which was the most direct evidence of the GVL effect. The novel in vitro TMP test in which the specific contribution of donor's leukocytes to the growth of recipient's hematopoietic precursor cell growth was determined, correlated with the clinical outcome.
Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics a... more Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: <2006 n=389 (9.4%), 2006-2010 n=910 (22%), 2011-2014 n=1148 (27.7%) and 2015-2018 n=1695 (40.9%). A steady increase in MF allo-HCT activity over time was apparent paralleled with increasing numbers of participating transplant centres. A total of 2603 (62.8%) patients were male, 3239 (78.2%) had Primary MF, 409 (9.9%) and 494 (11.9%) post-Polycythaemia Vera and post-Essential Thrombocythaemia MF, respectively. An increased median interval (lnterquartile range (IQR)) between diagnosis ...
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Papers by Dragana Stamatovic