Editorial

Dear colleagues and friends,

Doctors and all healthcare workers have always been uncompromising and tireless in preserving health and life. A part of this never-ending mission is searching within ourselves, which motivates us to learn fur- ther and give more.

One of the branches of medicine that deals with the most severe and complex diseases is hematology. This issue of the Serbian Journal of the Medical Chamber is dedicated to hematology and to all the readers who would like to learn more about hemato-oncological diseases, the challenges in establishing their diag- nosis, and modern therapeutic modalities. But first, let’s take a moment to go back in time...

The word hematology originates from the Greek words haima (αἷμα – blood) and logos (λόγος – sci- ence). The study of blood and its components has a lengthy history, as primitive man understood that the loss of blood, if copious enough, was associated with death. Also, in biblical references, “to shed blood” was a term denoting: “to kill.” In the period before microscopy, only the gross macroscopic appearance of blood could be studied. When observed in a glass container, the coagulated blood was seen to form different layers, and these layers were thought to make up the substance of the human body, while health and disease were seen as the result of the proper mixture of these layers or an imbalance among them. Microscopic examination of blood, first carried out by van Leeuwenhoek and his colleagues in the 17th century, using the first microscope, made it possible for scientifically proven knowledge to gradually re- place theory and dogma.

Over the past few decades, with the advancement of technology, automated molecular biological tech- niques have been developed, enabling electronic cell manipulation and the detection of genetic mutations which are the underlying cause of the altered structure and function of human cells and proteins, and as such, lead to hematological diseases.

The September issue of the Journal demonstrates how driven and enthusiastic researchers in this crucial branch of medicine are to publish their studies. After reviewing the manuscripts submitted and accepted for publication, I would especially like to thank all the authors of high-quality articles reporting original research results, as well as the authors who have submitted review articles and interesting case series.

This issue, which will reach its readers on the eve of the 6th Congress of Hematologists of Serbia with international participation, presents 17 articles: 7 original articles, 7 review articles, and three case reports. The topic of two of the original articles is acute myeloid leukemia (AML).

The first article, Prognostic and predictive significance of measurable residual disease in acute myeloblastic leukemia, by Jovan Rajić et al., analyzes the detection of residual leukemic cells via measurable residual dis-ease (MRD), originally named minimal residual disease. It has been proven that MRD represents the most important prognostic and predictive factor in acute myeloid leukemia, and the article further contributes to this topic. Namely, in this study, patients who continued treatment with intensive chemotherapy after a positive MRD status (MRD+) had significantly longer complete remission (CR) and overall survival (OS). Also, CR and OS were statistically significantly longer in patients who maintained a negative MRD status at the end of treatment.

The second article presents the study by Marijana Virijević et al., which retrospectively analyzes clinical characteristics and survival in adult patients with acute myeloid leukemia, through the experience of a ter- tiary institution. The authors demonstrated a low OS rate in patients treated with intensive chemotherapy. They also showed that age, AML subtype, and dysplastic characteristics, i.e. MRC (myelodysplasia-related changes), were unfavorable factors associated with shorter OS and shorter disease-free survival (DFS).

In their article, Natalija Kecman et al. analyze the development of febrile neutropenia (FN) in patients with hematological malignancies treated at the day-care unit of a tertiary institution. They demonstrated that a higher number of therapeutic lines and cycles of immunochemotherapy, the clinical stage of the dis- ease, the presence of bulky tumor mass, and the degree of lymphoma aggressiveness were associated with the development of febrile neutropenia.

The hematological toxicity of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) in the treatment of metastatic breast cancer, through the experience of a tertiary center, was analyzed in the study by Slo- bodan Kutić et al. In this article, it was shown that iatrogenic neutropenia occurred in 82.1% of patients treated with CDK4/6i, but discontinuation of therapy was rare. Also, palliative radiotherapy of bone lesions was associated with more frequent CDK4/6i dose reduction, however, the dose reduction of these drugs did not affect survival.

In their study, Nada Vlaisavljević et al. demonstrated that active concomitant therapy of insulin resistance in newly diagnosed patients with multiple myeloma (NDMM) could improve their therapeutic response to the applied antimyeloma treatment. Namely, the authors observed a statistically significant negative cor- relation between the fasting homeostatic model assessment-insulin resistance index (HOMA-IRIf) after treatment and the achieved therapeutic response.

A retrospective analysis of the clinical characteristics of patients with myeloproliferative neoplasms (MPN) under the age of forty is presented in the article by Isidora Arsenović et al. The study showed that the majority of patients belonged to the European LeukemiaNet (ELN) low-risk group, however, due to the de- velopment of thrombosis, existing complaints, and the degree of thrombocytosis and splenomegaly, almost 50% of these patients received cytoreductive therapy. The presented results indicate the need for better risk stratification, as well as the application of different methods of disease risk assessment, such as next-gener- ation sequencing (NGS).

Through the five-year experience of a single center, Vojin Vuković et al. have demonstrated that the ABVD chemotherapy regimen is not adequate for all patients with advanced-stage classical Hodgkin lym- phoma (AScHL). This retrospective study examines clinical and laboratory parameters, treatment, and pa- tient outcomes. The authors have concluded that a significant number of patients cannot be cured with the ABVD regimen, which is why it is necessary to provide them with more intensive treatment or innovative therapeutic modalities.

The first among the review articles, submitted by Zorica Cvetković et al., shows the importance of anemia in patients with heart failure and provides a detailed analysis of its multifactorial etiology, complex patho- physiology, and the specificities of the applied therapeutic approach.

The next article in this group, written by Nada Suvajdžić-Vuković and Mirjana Cvetković, focuses on drug-induced thrombocytopenia (DITP). The article analyzes the incidence and mechanisms of drug-in- duced thrombocytopenia occurrence, providing an individual description of the causative drugs, as well as a description of vaccine-induced thrombotic thrombocytopenia (VITT).

In their article, Nikica Sabljić et al. analyze the risk of bleeding as a potential problem with the use of di- rect oral anticoagulants (DOACs). They argue that the results of most studies show a lower risk of intracranial hemorrhage with the use of DOACs, as compared to the use of drugs from the vitamin K antagonists (VKA) group, as well as the same or even lower risk of major bleeding with the use of DOACs. In conclusion, the authors state that it seems that VKA drugs will gradually become obsolete, i.e., they will be used only in a certain, clearly defined population.

The review article, by Andrija Bogdanović and Danijela Leković, analyzes the literature on the current treatment of primary myelofibrosis (PMF). In their conclusion, the authors state that the treatment of this disease remains a challenge, that the use of ruxolitinib (the first representative of the Janus kinase inhibitor – JAKi) enables good control of the disease in almost half of the patients, and that new drugs should be able to treat refractory patients or improve therapeutic response.

Clinical manifestations associated with the presence of antiphospholipid (aPL) antibodies are the focus of the article written by Predrag Miljić et al. The article highlights the heterogeneity of the group of autoan- tibodies targeting anionic phospholipids or phospholipid-binding proteins, as well as their association with numerous clinical manifestations in almost all areas of medicine. The authors state that antiphospholipid syndrome (APS) is the most precisely defined entity characterized by the presence of said antibodies. They present the previous and the most recent classifications of the criteria for establishing the diagnosis of APS. Danijela Jovanović and Predrag Đurđević present the characteristics of a rare entity, light chain depo- sition disease, as one of the forms of monoclonal immunoglobulin deposition disease. The article analyzes the diagnostic criteria, clinical presentation (the most common being nephritic syndrome), and therapeutic modalities, while emphasizing a multidisciplinary approach, primarily by nephrologists, hematologists, and pathologists.

The clinical significance of ferroptosis, which was mentioned for the first time in 2012, is the subject of the article by Danijela Agić et al. It is a non-apoptotic, non-necrotic, and non-autophagic type of cell death dependent on iron, which requires the presence of lipid peroxides and is inhibited by ferrostatin. The authors searched the Medline database with special reference to articles dealing with the significance of ferroptosis in clinical medicine, primarily in hematology.

Interesting case studies, in the form of case reports with a literature review and case series, contributed to the comprehensiveness of this issue. Thus, Jelena Ivanović et al. presented the case of a patient diagnosed with Hodgkin’s lymphoma during pregnancy, as well as a review of the existing literature dealing with this issue. The authors point out that the treatment of Hodgkin’s lymphoma during pregnancy is a complex chal- lenge that requires a coordinated multidisciplinary approach and a personalized treatment plan.

Andrijana Kojić and Mila Purić present two patients with multiple myeloma diagnosed with central ner- vous system involvement (CNS-MM). This entity is quite rare, accounting for less than 1% of extramedullary multiple myeloma, and manifests as a variety of neurological deficits. The authors conclude that, despite advances in diagnostics and treatment, the prognosis of CNS-MM remains poor owing to the complex and aggressive clinical course of the disease, at the same emphasizing that further research is necessary, due to low incidence and limited data.

The article reporting on disease progression in three patients with low-risk primary myelofibrosis (PMF) is presented by Mihailo Smiljanić et al. Although the median survival of these patients is more than 15 years, according to the MOST prospective study, almost 60% have disease progression, which is why the authors aimed to present the course of the disease and treatment through the case reports. Due to the above-stated characteristics of the disease, the authors conclude that there is a need for further research that would show whether early NGS analysis of non-driver mutations and early initiation of therapy contribute to a change in the course of the disease.

We hope that this themed issue of the Journal, heralding the upcoming Congress of Hematologists, will bring the complexity of the subject of hematology closer to all our readers and highlight the dedicated work of an entire team of experts, as well as the importance of continuous improvement. All this is, in fact, a part of the constant pursuit and a reflection of personal and professional progress, all for the benefit of hematology patients.

Sincerely