Presence of minimal residual disease determined by next-generation sequencing is not a reliable prognostic biomarker in children with acute lymphoblastic leukemia.

The role of next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric acute lymphoblastic leukemia (ALL) is still under consideration. Fifty pediatric patients were prospectively evaluated for specific clonal rearrangements of immunoglobulin and T-cell receptor genes using NGS analysis at diagnosis and on days 33 and 78 from therapy onset. The prognostic value or the NGS-MRD status was analyzed after a median follow-up of 4 years.

Effectiveness of Ropeginterferon Alfa-2B in High-Risk Patients with Philadelphia Chromosome Negative Myeloproliferative Neoplasms- Evaluation of Clinicohaematologic Response, and Safety Profile: Single Centre Experience.

requires individualized approach depending on multiple factors. Novel pegylated Interferon (IFN) formulations have become an attractive therapeutic option in young Ph- MPN patients associated with better patient compliance. : In this retrospective observational study a total of 16 high-risk Ph- MPN patients treated off-label with ropeginterferon alfa-2b given twice monthly, were included.

Gaucher disease in North Macedonia: Unexpected prevalence of the N370S GBA1 allele with attenuated disease expression.

The majority of Gaucher Disease (GD) cases result from pathologic mutations in the GBA1 gene. A rich mutational spectrum of about 500 identified variants has been recognized. The disease is characterized by phenotypic diversity.

Early-Onset Colorectal Cancer in a Young Woman with Type 1 Gaucher Disease.

Introduction: Gaucher disease (GD) is a rare inherited lysosomal storage disease characterized by multi-system impairment. One of its main features is the over-expressed chronic stimulation and activation of the immune system, which may play a crucial role in the development of some malignancies associated with GD.

Case Description: We describe a young woman diagnosed with GD type 1 in early adulthood who developed early-onset colorectal cancer shortly after GD diagnosis and the initiation of enzyme replacement therapy.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

Background: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis.

Management: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population.

Insight in the Current Progress in the Largest Clinical Trials for Covid-19 Drug Management (As of January 2021).

The outbreak of the COVID-19 pandemic has generated the largest global health crisis of the 21st century, evolving into accelerating socioeconomic disruption. In spite of all rapidly and widely emerging scientific data on epidemiology, diagnosis, prevention and treatment of the COVID-19 disease, severe acute respiratory coronavirus 2 (SARS-CoV-2) is continuing to propagate in lack of definitive and specific therapeutic agents. Current therapeutic strategies are mainly focused on viral inhibition by antiviral drugs and hampering the exuberant immune response of the host by immunomodulatory drugs.

Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor - Hematopoietic Stem Cell Transplantation: Single Center Experience.

Introduction: Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) cases is a complex, multi-modality process and, though much of its clinical implications at different points are extensively studied, it remains even now a challenging area. It is a disease the biology of which governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. On the other hand, relapse is considered as the leading cause of treatment failure in AML patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT).

Clinical Characteristics and Treatment Results of Childhood Acute Lymphoblastic Leukemia in North Macedonia.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. This study was designed to determine the clinical, biological features and outcomes among children with ALL treated at the only pediatric hematology-oncology center in North Macedonia.

Patients And Methods: Seventy four consecutive children age 1 to 14 years, diagnosed with ALL between January 1, 2010 and October 31, 2017 and treated according to ALL IC BFM 2002 protocol were retrospectively evaluated.

The use of remdesivir outside of clinical trials during the COVID-19 pandemic.

With a scientific background from filoviruses, paramyxoviruses, SARS-CoV, and MERS-CoV, remdesivir entered into the COVID-19 battle to become one of the favorable therapeutic candidates with potential antiviral activity in the treatment of this disease. Globally, remdesivir was accessed and investigated through clinical research (clinical trials) and clinical practice (compassionate use, expanded access, early access scheme, and emergency use). Currently, remdesivir approval status differs between states.

Current regulatory approaches for accessing potential COVID-19 therapies.

This commentary aims to elaborate challenges in the regulatory approaches for accessing and investigating COVID-19 potential therapies either with off-label use, compassionate use, emergency use or for clinical trials. Since no therapies have been formally approved and completely effective and safe to date, the best clinical choice is acquired only after consistent and fair communication and collaboration between licensed clinicians, researchers, regulatory authorities, manufacturers and patients.

Evaluation of the JAK2V617F Mutational Burden in Patients with Philadelphia Chromosome Negative Myeloproliferative Neoplasms: A Single-center Experience.

The identification of the JAK2V617F mutation in several distinct myeloproliferative neoplasms (MPNs) raised the question how one single mutation incites expression of at least three different clinical phenotypes, ., polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In order to further evaluate already published data on the correlation between mutant JAK2V617F allele burden and specific hematological and clinical parameters, we tested the level of the JAK2 mutation in 134 JAK2+ patients with different MPNs.

A Rare Case of Soft Tissue Erdheim Chester Disease: Diagnostic Dilemma and Management.

Background: Erdheim Chester disease (ECD) is a rare form of non-Langerhans histiocytosis that still presents a diagnostic and clinical dilemma.

Case Presentation: We present a rare case of ECD, young 31 male with atypical localisation and soft tissue presentation and no bone involvement. He started clinical investigations due to subcutaneous tumour mass in the lumbar spine that caused severe back pain.

Moleculary Confirmed, Cytogenetic Remission in a Case with Myelodysplastic Syndrome Treated with Azacitidne.

Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic neoplasms. The only curative treatment for MDS is allogeneic stem cell transplantation (SCT). Epigenetic changes play an important role in the pathogenesis of MDS and treatment with DNA methyl transferase inhibitors, Azacitidine, significantly prolong the survival of high-risk MDS patients.

Diversities of Calreticulin Gene Mutations in Macedonian Patients With Essential Thrombocythemia.

Background: Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype.

Patients And Methods: We evaluated the clinical and molecular features of 150 patients with ET followed over a period of 15 years.

Multivariable model consisting of clinical and biological markers for time to first treatment in CLL patients: Preliminary results from single centre experience.

Introduction: The clinical course for patients with chronic lymphocytic leukaemia (CLL) is extremely heterogeneous; one of the most important challenges in the clinical management of these patients is the decision on initiating their treatment, but there is no available prognostic system that will resolve this issue. Usually, criteria for active disease are used to initiate therapy. Recently, some authors have proposed prognostic models, scoring systems involving a set of clinical and biological risk factors and estimates of individual patient survivals.

Haematology in the Republic of Macedonia: present situation and brief history.

The development of clinical haematology in Macedonia has taken place over the past nine decades. The greatest expansion of its development took place in the second half of the 20th century. The oficial start of clinical haematology dates from 1956, when the Department of Haematology was founded within the framework of the Internal Medicine Clinic in Skopje.

Minimal screening analysis based algorithm for diagnosis and clinical stratification of patients with acute myeloid leukaemia (AML): single centre experience.

In this paper we present our results from a study designed in order to establish and standardize a diagnostic algorithm for acute myeloid leukaemia (AML) in the Republic of Macedonia. A total of 146 consecutive adult patients (>15 years) were enrolled in the study. First, we determined the correct lineage assignment of the blast cells and evaluated the incidence of the favourable PML/RARα, AML1/ETO, CBFβ/MYH11 genetic markers among the AML cases.

A case report of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome.

A case of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome is described. Pancytopenia and circulating blasts cells at presentation suggested the diagnosis of acute leukemia in the previously healthy 38 years old Caucasian male patient, but flow-cytometry analysis of the bone marrow disclosed the correct diagnosis of neuroblastoma. The immunophenotype was CD45-/CD56+/CD9+ in around 50% of the mononuclear cells, indicating neuroectodermal origin of the malignant cells.

JAK2V617F mutations in myeloid malignancies: single center experience.

Recently, V617F mutation in JAK2 tyrosine kinase gene was established as a marker of myeloproliferation, useful for proving clonality and securing diagnosis in a considerable proportion of the myeloproliferative neoplasms (MPN) The discovery presents a major breakthrough in the understanding of the pathogenesis of the MPN. Moreover, some studies suggest a possible role of the JAK2V617F mutation in the pathogenesis of some specific acute myeloid leukemia (AML) subtypes. To further improve the understanding of the role of JAK2V617F mutations in the pathogenesis and the clinical course of the myeloid malignancies we screened 192 patients with various MPN and AML for the mutations and analyzed the possible association between JAK2V617F mutations and the clinical features of MPNs patients.

Prognostic value of immunoglobulin variable heavy chain gene mutation status: long term follow-up in a series of chronic lymphocytic leukemia patients.

B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. Classical staging systems and laboratory features help predict survival in CLL, but they do not distinguish patients who will progress from those whose disease will remain indolent. In recent years, new molecular prognostic factors have emerged that have significantly improved prediction of the risk for disease progression.