Documenta Haematologica - Revista Romana de Hematologie最新文献

{"title":"Natural Killer cells at war: Unravelling the role of NK cells in acute myeloid leukemia","authors":"V. Cianga, Cătălin Doru Dănăilă, I. Antohe, Mariana PAVAL-TANASA, P. Cianga, C. Rusu","doi":"10.59854/dhrrh.2023.1.2.65","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.65","url":null,"abstract":"Natural Killer (NK) cells play a major role in the immune response against cancer, including hematological conditions such as myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). This review explores the impact of the leukemic microenvironment on NK cell subsets in AML and MDS, shedding light on their potential implications in disease progression. In AML, studies have revealed a maturation blockade of NK cells in the altered bone marrow microenvironment, while NK cells from peripheral blood have the tendency to differentiate all the way to the final stages. The leukemic microenvironment not only affects NK cells but other immune compartments as well, including T cells. Therefore, a phenomenon of effector cell exhaustion has been described for both T cells and NK cells in AML, leading to compromised immune responses. Furthermore, altered expression of inhibitory receptors, such as NKG2A and KIR, on NK cells in AML and MDS suggests a potential involvement of leukemic cells in the preferential expression of key inhibitory molecules on the surface of these effectors. The dysregulated cytokine milieu within the leukemic microenvironment may account for the changes in receptor expression patterns, influencing both NK cell cytotoxicity and secretory functions. In conclusion, the leukemic cells and altered microenvironment have profound effects on NK cell subsets in both AML and MDS, affecting their maturation, function, and phenotype. Understanding these interactions may provide insights into novel therapeutic approaches to enhance the anti-tumoral immune response and improve outcomes for these patients.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"42 5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124970528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of HALP score in the determination of nodal non-Hodgkin lymphoma prognosis","authors":"V. Tomacinschii, S. Buruiana, M. Robu","doi":"10.59854/dhrrh.2023.1.2.51","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.51","url":null,"abstract":"Introduction: Non-Hodgkin’s lymphomas (NHL) are hematopoietic tumors that develop from the malignant proliferation of the lymphatic tissue. The onset of NHL can occur in any organ and tissue, at the same time the most frequent localization is represented by the primary involvement of the lymph nodes (52-70%). The hemoglobin, albumin, lymphocytes, and platelets compose a score (HALP score), have recently been evaluated to predict the prognosis of cancer patients. However, there are limited reports of the use of HALP score in the determination of survival prognosis with NHL. Objective: This study aims to appreciate the usefulness of the HALP score in the determination of overall survival (OS) indicators in patients with nodal non-Hodgkin’s lymphomas. Material and methods: 57 patients diagnosed with nodal NHL in the Oncology Institute of the Republic of Moldova have been evaluated. The HALP score was calculated using formula: hemoglobin (g/L) × albumin (g/L) × lymphocytes (%) / platelets (/L). Results: Out of the patients enrolled in study 35 (61.4 %) were female. Aggressive lymphomas were diagnosed in 45 cases (78.9%), and indolent lymphomas in 12 patients (21.1%). On receiver operating characteristic curve (ROC) analysis, the predictive ability of the HALP score to envisage the risk of unfavorable events was significant (p= 0.038; AUC:0.685). The cut off value based on ROC was 583,5. As a result, it was observed that in case of aggressive NHLs HALP patients with a low HALP score have a shorter period of OS: median OS-13(4,4) months compared with the group of patients with high HALP score where the median OS was not reached, p=0,049. In contrast, in indolent lymphomas, HALP score failed to show significant differences in survival between groups of patients with high or low HALP score(p=0,081). Conclusions: The HALP score, appears to be a valuable tool in determining the prognosis of patients with nodal NHL. A low HALP score was associated with lower OS rates - 13(±4,4) months in case of aggressive NHLs. (p=0,049). However, in case of indolent NHLs HALP score failed to perform as a useful prognostic score in the estimation of OS.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129982687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Molecular Mechanisms Involved in Hepatitis B Virus Associated B-cell NonHodgkin Lymphoma (B-NHL)","authors":"Mihaela Uta, A. Ghionescu, Codruţa Popa, N. Nichita, D. Coriu","doi":"10.59854/dhrrh.2023.1.2.59","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.59","url":null,"abstract":"The Non-Hodgkin Lymphoma (NHL) is a heterogeneous group of malignancies ranked as the most common haematological cancer worldwide, more than 544 000 new cases being reported in 2020. More recent epidemiological studies have shown an increased risk of several types of B-cell Lymphoma development, the most prevalent being diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) subtypes, in patients infected with hepatitis B virus (HBV). These patients are more difficult to treat and their survival rate is lower compared to uninfected people. HBV is known as a hepatotropic virus, although viral HBV-DNA has been identified in extrahepatic tissues, such as kidney, pancreas or peripheral blood mononuclear cells (PBMC). However, the mechanistic relationship between HBV infection and lymphoid cancer is not known. Preliminary data have shown that NTCP, the specific HBV receptor is expressed in normal B cells. After exposure to HBV viral particles, B cells become capable of producing viral core antigens (HBcAg). Antiviral roles and/or cancer-promotion functions in B-cells of APOBEC3 deaminases overexpression remain to be determined.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"130 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123131360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of MIR-4328 gene mutations in Acute Promyelocytic Leukemia","authors":"Onda-Tabita Calugaru, M. Dragomir, Silvia Aposteanu, Cerasela Jardan, Alina Cristiana Meirosu, D. Coriu","doi":"10.59854/dhrrh.2023.1.2.37","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.37","url":null,"abstract":"Introduction: miRNAs are involved in the pathogenesis of neoplastic syndromes by silencing target genes. As previously shown, hsa-mir-4328 is downregulated in Acute Promyelocytic Leukemia (APL). Objectives: The study aims to identify the somatic mutations of the MIR-4328 gene that caused its downregulation in APL and their localization in key regions of the mature miRNA structure. Material and methods: The study included 24 subiects: the study group (10 patients at the onset of APL, as well as at remission and relapse) and the control group (10 apparently healthy patients). High-Resolution Melting (HRM) was used for genotyping. Results: As MIR-4328 gene has not been studied before, a structure design of the coding region was performed to better understand the impact of somatic mutations on the mature miRNA. Following HRM, 2 mutant genotypes were identified, different from the wild-type (WT) genes. Conclusions and discussion: Due to the major deviation of the mutant genotypic curves compared to WT, the existence of major mutations (probably insertions/deletions) can be assumed. If these mutations are located in the seed region of the gene, attachment to exon 3 of the RARA gene is no longer possible, and therefore overexpression of the target gene occurs. Also, frameshift mutations, or substitutions that change the nucleotide sequence of the seed region, can produce a completely different mature miRNA that may have tropism for another gene. To test these hypotheses, sequencing of the entire gene is required.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121048664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenalidomide and Carfilzomib in Relapsed and Refractory T Follicular Helper Lymphomas","authors":"Alina Marina Dimcea, Miruna Elena Tarnovan, Adina Florentina Stemate, A. Bardaş, C. Dobre, D. Coriu","doi":"10.59854/dhrrh.2023.1.2.73","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.73","url":null,"abstract":"Non-Hodgkin T-cell lymphomas represent a heterogeneous group of aggressive haematological malignancies with a high risk of early relapse or resistance to standard treatment protocols. One significant drawback is that chemotherapy protocols were initially designed for B-cell lymphomas, and targeted studies for T-cell lymphomas were only recently developed. Due to the rising incidence of peripheral T cell lymphomas (PTCL) in recent years, there is a need for new therapies to effectively treat these types of malignancies. Incorporating gene expression profile (GEP) studies in the standard diagnostic tests could enable treatments specifically tailored to each patient's needs. In this article we present the case of a patient diagnosed nodal-T follicular helper cell lymphoma, who exhibited early relapse following the standard chemotherapy protocol in our country. After multiple lines of treatment without favorable response, we conducted an off-label treatment combining Lenalidomide (an immunomodulatory drug) and Carfilzomib (a selective irreversible proteasome inhibitor). This therapeutic approach was previously done in other studies, but it involved also the use of Romidepsin, a histone deacetylase inhibitor (HDACi). We did not use Romidepsin in this patient as it is not approved in the European Union for patients with PTCL.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124080348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of the Number of Copy Numbervariations by Mlpa Technique in Acute Lymphoblastic Leukemia","authors":"A. Titieanu, V. Cianga, Cătălin Doru Dănăilă, M. Dragos, I. Ivanov, A. Dascalescu","doi":"10.59854/dhrrh.2023.1.2.43","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.2.43","url":null,"abstract":"Introduction: Acute lymphoblastic leukemia (ALL) is a hematological malignancy with a higher frequency in children than in adults. Adult ALL is associates with increased morbidity and mortality and a significantly lower survival rate compared to its pediatric counterpart with an average survival of 40% at 5 years. The prognosis of patients with ALL is determined by multiple factors, such as age, tumor syndrome, white blood cell counts, cytogenetic abnormalities, and therapeutic response. The Multiplex Ligation dependent Probe Amplification technique (MLPA) is used to determine the copy number variations (CNV) of several key genes involved in disease progression and resistance, such as IKAROS family zinc finger 1 (IKZF1), PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A/2B, CRLF2. In this study, we sought to investigate the relationship between these genetic markers and standard prognostic factors in a small cohort of adult ALL patients with the aim of improving our risk stratification strategies. Materials and Methods: We investigated a group of 29 patients diagnosed with B- ALL at the Hematology Clinic of the Iasi Regional Oncology Institute between 2017 and 2021. DNA extraction and MLPA analysis were performed according to the standard technical protocol. Results: MLPA analysis reported deletions in 61% of cases and duplications in 39% of the investigated cases. The most frequent deletion identified was IKZF1 (31 %), followed by CDKN2A/2B (24.1 %), PAX5 (17.2 %), RB1 (17.2 %), ETV6 (10.3%) and, lastly, JAK2 (6.9 %). Conclusions: Our study demonstrated similar CNV profiles as in the literature data, which proves that these mutations could potentially play a role in a more sensitive risk stratification score.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121033376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 infection in a patient with Follicular non-Hodgkin Lymphoma. A Case Report","authors":"D. Popovici, Sandra Monica Lazar, Alina-Maria Ilie, Larisa Marina David, Oana Sarau, Dacian Nicolae Oros, C. Ionita, Sorin Dema, N. Balica, I. Ioniţă","doi":"10.59854/dhrrh.2023.1.1.19","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.1.19","url":null,"abstract":"Follicular non-Hodgkin Lymphoma (FNHL) is the most common type of indolent non-Hodgkin Lymphomas (NHL) that develops from abnormal B-lymphocyte that form follicle-like clusters inside the lymph nodes (1). The prevalence of FNHL is estimated around 1 in 3000 patients, being usually encountered in elderly, 60 years old patients and diagnosed in advanced stages when monoclonal antibodies alone or combined with other chemotherapy agents are needed (2). Recent studies about COVID-19 infection prognosis suggest that oncologic patients are at high risk of morbidity and mortality due to SARS-CoV-2 infection, partially because of the secondary immune deficiency due to malignant pathology itself, but also to the accumulated toxicity secondary to the immuno-chemotherapy treatment. (3). This case report describes a young female patient with FNHL with Bulky abdominal tumoral mass detected at CT scan, in Complete Remission after immune-chemotherapy treatment, contacting COVID-19 twice, first in 2020 and second time in 2022. Even if the patient has been vaccinated against SARS-CoV-2 in late 2021, she did not develop an increased titer of either SPIKE anti-protein neutralizing antibodies (Protein S) or anti-Nucleocapsid IgG antibodies.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133740427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold Agglutinin Disease – Diagnostic and Therapeutic Challenges in the Clinical Setting","authors":"C. Șaguna, Alexandra Oana Enache, Maria Bubulete, Mariana Racila, A. Colita, N. Berbec, Virginia G. Marín, Elena-Sabina Bălan, R. Manolache, D. Barbu, S. Angelescu, O. Stanca, A. Lupu","doi":"10.59854/dhrrh.2023.1.1.7","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.1.7","url":null,"abstract":"Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA), in which IgM specific antibodies cause the agglutination of red blood cells (RBCs) at temperatures < 37°C and activate the classical pathway of complement leading to extravascular hemolysis, C3b-coated RBCs are phagocytosed by the macrophages of the reticuloendothelial system (predominantly in the liver). Up to date there are two clinical-pathologic entities recognized as distinct with different therapeutic implications: cold agglutinin disease and cold agglutinin syndrome (CAS). Primary CAD is recognised as clonal B-cell lymphoproliferative disorder of the bone marrow, clinical and imagistic evidence of associated malignancy. CAS arises in the setting of an underlying disorder such as infection, autoimmune disease or malignancy (non Hodgkin lymphoma or other malignant process). The diagnosis of CAD is often delayed due to the unpredictable clinical course. In spite of the current therapeutic options which are directed at the pathogenic B cells or the complement system, the low response rates and frequent relapses lead to challenges regarding the management of this disease.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131121760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Philadelphia chromosome positive de novo AML or blast phase CML?","authors":"D. Soare, Georgiana Elena Ene, D. Diaconescu, Delia Soare, C. Enache, Cristina Mambet, I. Dumitru, Madalina Cirnu, A. Vlădăreanu, E. Radu, H. Bumbea","doi":"10.59854/dhrrh.2023.1.1.25","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.1.25","url":null,"abstract":"The BCR::ABL1 translocation and the accompanying Philadelphia chromosome represents the first mutation which defined a disease, chronic myeloid leukemia. It also represents the first druggable target for which a specific compound was developed and accepted in current clinic practice, imatinib. Despite these, there are still areas in which the diagnosis and the best treatment sequence still needs investigation. One such context is the diagnosis and management of BCR::ABL1 positive myeloid neoplasms with ≥20% blasts, more specifically the differentiation between myeloid blast phase chronic myeloid leukemia and BCR::ABL1 positive acute myeloid leukemia. In this paper we present our recent experience with a BCR::ABL1 positive myeloid neoplasms with ≥20% blasts.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130905190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelomatous Meningitis - a diagnostic and therapeutic challenge","authors":"Sinziana Barbu, R. Irimia, M. Popescu, Diana Preda, A. Jercan, D. Coriu, S. Badelita","doi":"10.59854/dhrrh.2023.1.1.13","DOIUrl":"https://doi.org/10.59854/dhrrh.2023.1.1.13","url":null,"abstract":"Multiple myeloma is a malignant disease, which consists of the clonal proliferation of plasma cells that will lead to the accumulation of a monoclonal protein in the serum and/or urine, with organic damage. Extramedullary involvement is found in approximately 5% of cases of myeloma. Multiple myeloma with determination in the central nervous system is extremely rare and is associated with a bad prognosis. A targeted treatment scheme for this complication is not described, but the therapeutic approach should follow the same steps as in the case of other lymphoproliferative diseases with neurological involvement ( association of intrathecal chemotherapy applications cytarabine and methotrexate, with systemic treatment and depending on the response local radiotherapy should be performed). The occurrence of extramedullary disease in the evolution of multiple myeloma is a complication associated with a poor prognosis.","PeriodicalId":425250,"journal":{"name":"Documenta Haematologica - Revista Romana de Hematologie","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115290094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}