Srpski medicinski časopis Lekarske komore

PROGNOSTIC AND PREDICTIVE SIGNIFICANCE OF MEASURABLE RESIDUAL DISEASE IN ACUTE MYELOBLASTIC LEUKEMIA

Jovan Rajić — 2024-09-19

Introduction: Acute myeloblastic leukemia (AML) is an umbrella term for a heterogeneous group of clonal neoplastic diseases of hematopoietic cells. Detecting residual leukemic cells (measurable residual disease – MRD) is the most important prognostic and predictive factor in AML.

The aim: The study aims to analyze the effect of administered chemotherapy based on the results of MRD testing in patients with AML treated at the University Clinical Center of Serbia (UCCS) Clinic for Hematology.

Materials and Methods: Our study included the analysis of 111 AML patients, treated between January 2020 and January 2024. All diagnostic procedures performed were based on the most recent recommendations of European LeukemiaNet (ELN).

Results: MRD+ patients who continued treatment with intensive chemotherapy (CHT), using full doses of 3+7 CHT as reinduction therapy, had a significantly longer remission (complete remission – CR) and a longer overall survival (OS). The duration of CR (p = 0.004) and OS (p = 0.019) were statistically significantly longer in patients who maintained a negative MRD status at the end of treatment. In transplanted patients, overall survival (OS; p = 0.006) and duration of remission (CR; p = 0.002) were significantly longer (median: OS 20 months; CR 21 months), as compared to the group of non-transplanted patients (median: OS 13 months; CR 8 months).

Discussion: Measurable residual disease (MRD) can be both prognostic and predictive. However, the absolute measurable level of the disease is not the only determinant of the patient's outcome, since the biology of AML, as well as other clinical patient-related factors (age, comorbidities, various complications of applied chemotherapy, especially infections), modify the risk associated with MRD test results.

Conclusion: The study has demonstrated the great importance of timely detection of MRD, as well as the appropriateness of applying more intensive CHT in MRD-positive patients, along with continued treatment with allogeneic hematopoietic stem cell transplantation.

CLINICAL CHARACTERISTICS AND SURVIVAL OUTCOMES IN ACUTE MYELOID LEUKEMIA PATIENTS: SINGLE CENTER EXPERIENCE

Marijana Virijević — 2024-09-22

Introduction/Aim: Acute myeloid leukemia (AML) is a heterogeneous disease, in terms of its biological characteristics and response to therapy. Numerous prognostic factors at diagnosis related to the disease itself, the treatment, and the response to treatment influence the outcome of AML. Despite the high rate of complete remission, overall survival (OS) is still poor. This study aims to determine the clinical and biological profile of patients with AML and its prognostic impact on the OS rate and disease-free survival (DFS).

Materials and Methods: The retrospective analysis included 271 patients diagnosed with acute myeloid leukemia at the University Clinical Center of Serbia (UCCS) Hematology Clinic, between January 2018 and January 2023. Demographic parameters, the Eastern Cooperative Oncology Group performance status (ECOG PS), comorbidities, and the parameters of laboratory analysis and hematological diagnosis of AML were analyzed as potential risk factors for OS and DFS, using the univariate Cox regression model.

Results: Out of a total of 271 patients, 206 (76%) were treated with intensive chemotherapy, of whom 108 were men and 98 were women. The average age of these respondents was 50.3 years. According to the European Leukemia Network (ELN) risk classification, the patients were mostly in the group with intermediate risk, i.e. 128 (62.1%) patients. The most common subtype of AML was AML NOS (AML not otherwise specified), present in 123 (59.7%) patients. Univariate analysis showed that age ≥ 60 years (p = 0.009) and WBC ≥ 30 x 10⁹/l (p = 0.031) were unfavorable prognostic parameters for OS. AML subtype, MRC (myelodysplasia-related changes) was the most significant risk factor for shorter disease-free survival (p = 0.027).

Conclusion: In the analyzed group of AML patients treated with intensive therapy, we demonstrated a low OS rate and showed that age and the MRC subtype of AML represent unfavorable risk factors for shorter OS and DFS, respectively.

FREQUENCY AND SIGNIFICANCE OF THE DEVELOPMENT OF FEBRILE NEUTROPENIA IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES TREATED IN THE DAY-CARE UNIT OF A TERTIARY INSTITUTION

Natalija Kecman — 2024-09-15

Introduction: Chemotherapy-induced neutropenia is often complicated by the development of febrile neutropenia (FN) which is associated with infections, dose reductions/delay of chemotherapy, quality of life deterioration, and increased treatment costs.

Aims: The study aims to research the association between risk factors for FN and the significance of applying G-CSF in patients with hematological malignancies.

Methods: We evaluated 90 patients with lymphoma, multiple myeloma (MM), and myelodysplastic syndrome (MDS) treated at the Day-care Unit of the University Clinical Center of Serbia (UCCS) Clinic for Hematology, between January and June 2024.

Results: The study included 90 patients with the following diagnoses: 70 (77.8%) patients with lymphomas, 12 (13.3%) patients with MM, and 8 (8.9%) patients with MDS, of whom 42.2% (38/90) male and 57.8% (52/90) female. Febrile neutropenia (FN) was observed in 22 (24.4%) patients, while 68 (75.6%) patients did not develop FN. The distribution of FN by lymphoma type was as follows: 57.9% in aggressive lymphomas, 31.6% in indolent lymphomas, and 10.5% in Hodgkin's lymphoma. FN was associated with a higher incidence of advanced clinical stages of disease, with 70% in stages III and IV. Patients with FN had significantly higher rates of bulky tumor mass (54.5% vs. 25%; p = 0.010), more lines of chemotherapy (p = 0.020), more cycles of chemotherapy (p = 0.027), more immunotherapy cycles (p = 0.025), as well as more infections (59.1% vs. 27.9%; p = 0.008), antibiotic use (95.5% vs. 33.8%; p = 0.004), and G-CSF administration (54.5% vs. 11.8%; p < 0.001), with more G-CSF ampoules used (5.0 vs. 1.0; p < 0.001). Higher CRP levels were also significantly associated with FN (7.2% vs. 3.3%; p = 0.012).

Conclusion: Our study has shown that the number of lines of therapy, the number of immunochemotherapy cycles, the clinical stage, the presence of bulky tumor mass, and the aggressiveness of the lymphoma affected FN development.

HEMATOLOGICAL TOXICITIES OF CYCLIN-DEPENDENT KINASE 4 AND 6 INHIBITORS IN METASTATIC BREAST CANCER, SINGLE INSTITUTION EXPERIENCE

Slobodan Kutić — 2024-09-18

Introduction: Hematologic toxicity is the most common side effect of CDK4/6 inhibitors (CDK4/6i). Due to the novelty of these drugs, additional data are needed to identify potential predisposing factors for the development of hematologic toxicities.

Aim: This study aims to investigate potential predisposing factors for the development of hematological toxicity during the administration of CDK 4/6i in the treatment of metastatic breast cancer.

Methods: This retrospective descriptive study investigated the application of CDK4/6i in patients with metastatic breast cancer treated at the Breast Department of IORS from 1.1.2021 to 1.6.2024.

Results: 128 patients were included in the study; 43% were treated with palbociclib and 57% with ribociclib. The median age was 60 years. Median follow-up was 12 months (range 2-23). Neutropenia was observed in 82.1% of patients and grade 3/4 in 43%. Dose reduction due to repeated grade 3/4 neutropenia was required in 21.1% of subjects. Grade 3/4 anemia and thrombocytopenia were observed in 0.8% and 1.6% of patients. Discontinuation of therapy due to hematological toxicities was necessary in 1.5% of patients. There was no statistically significant difference between the two drugs regarding the incidence of hematological toxicity (p=0.443). Previous use of chemotherapy in the metastatic phase of the disease was not significantly associated with the frequency of hematological toxicity (p=0.565). Palliative radiotherapy of bone lesions showed a statistically significant association with the need to reduce the dose of CDK4/6i (p=0.001, r=0.283). Median progression-free survival (PFS) was not reached, but there was no trend to suggest that CDK4/6i dose reduction affected PFS (p=0.719).

Conclusion: Palliative radiotherapy of bone lesions is associated with more frequent dose reduction of CDK4/6i, but dose reduction of these drugs did not affect the length of survival.

THE INFLUENCE OF INSULIN RESISTANCE ON THERAPEUTIC RESPONSE IN NEWLY DIAGNOSED PATIENTS WITH MULTIPLE MYELOMA

Nada Vlaisavljević — 2024-09-19

Introduction: According to the results of previous research, it was found that the dysfunction of the insulin-like growth factor (IGF) system, which is the basis of insulin resistance with hyperinsulinemia, acts as a proliferative tumor factor, and its neoplastic potential is also exhibited in multiple myeloma.

Study aim: The study aims to determine whether there is an association between insulin resistance in patients newly diagnosed with multiple myeloma (NDMM) and the achieved therapeutic response after induction chemotherapy.

Materials and methods: The prospective study included 35 NDMM patients (60% women and 40% men), treated at the Clinical Center of Vojvodina Clinic for Hematology. Glycemia and insulinemia levels were determined after fasting and postprandially, upon which the values of HOMA-IRIf (after fasting) and HOMA-IRIpp (postprandially) were calculated. HOMA-IRI values > 2.2 were the criteria for insulin resistance. The analyses were performed twice – before the initial chemotherapy and after the completion of the treatment. The therapeutic response was evaluated according to the criteria of the Serbian Myeloma Group (SMG) and the International Myeloma Working Group IMWG). Statistical analyses were performed in the SPSS program, Version 22.

Results: The average patient age was 63.85 years. In total, 86% of patients responded favorably to the therapy. The average value of HOMA-IRIf before treatment was 1.82 ± 0.79 and it was 1.80 ± 0.72 after therapy. The central median value of HOMA-IRIpp before treatment was 5.46, with an interquartile range of 1.07 – 20.57, and after treatment, it was 5.86 with an interquartile range of 1.22 – 28.22. A significant negative correlation between HOMA-IRIf after applied treatment and achieved therapeutic response was observed, (p = 0.040).

Conclusion: Active concomitant therapy of insulin resistance in NDMM could improve the response to applied antimyeloma treatment.

MYELOPROLIFERATIVE NEOPLASMS IN PATIENTS YOUNGER THAN 40 YEARS: A RETROSPECTIVE ANALYSIS OF CLINICAL CHARACTERISTICS

Isidora Arsenović — 2024-09-24

Introduction: Myeloproliferative neoplasms (MPN) are typically diagnosed in patients around 60 years of age; however, in clinical practice, patients < 40 years are often encountered.

Aim: Assessment of clinical-laboratory characteristics, thrombosis incidence, and therapeutic approaches in patients with MPN < 40 years.

Methods: This retrospective study included 84 patients diagnosed according to WHO criteria who were treated at the Clinic of Hematology, UCCS, from 2000 to 2024.

Results: The median age was 33 years, with a higher prevalence in females (60.7%). Polycythemia vera (PV) was found in 61.9%, essential thrombocythemia (ET) in 25%, and pre-primary myelofibrosis (prePMF) in 13.1% of participants. The JAK2V617F mutation was detected in 46.5% of patients. Microvascular symptoms were present in 27.4%, pruritus in 14.3%, constitutional symptoms in 7.1%, and splenomegaly in 45.2% of patients. The highest hemoglobin and hematocrit levels were found in PV patients (170 g/L, 50%). The platelet count was highest in patients with prePMF (1007x10⁹/L), followed by ET (856x10⁹/L) and PV (737.5x10⁹/L). The distribution of bone marrow fibrosis was as follows: MF0 – 28.5%, MF1 – 54.8%, MF2 – 4.8%. Overall, 41.7% of patients had at least one cardiovascular risk factor, most commonly smoking (23.8%). The previous thrombosis occurred in 16.7% of patients, while thrombosis during follow-up (8.3%) was seen only in PV patients. Aspirin was used by 86.9% of patients, and phlebotomy was applied to almost all PV patients. Cytoreductive therapy was used in 43.9% of patients, with 39.1% receiving one line of treatment, most commonly hydroxyurea (HU). According to the ELN score, 82.1% of patients were classified as low-risk. The median follow-up was 72 months, and two patients died (2.45%).

Conclusion: The majority of younger MPN patients belong to the low-risk ELN group. However, nearly half of the patients receive cytoreductive therapy due to the development of thrombosis (25%), the presence of symptoms, the degree of thrombocytosis, and splenomegaly > 18 cm. This indicates the need for better stratification and the use of different methods for disease risk assessment, such as next-generation sequencing (NGS).

ABVD DOES NOT FIT ALL ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA PATIENTS: REAL-WORLD FIVE-YEAR SINGLE-CENTER EXPERIENCE

Vojin Vuković — 2024-09-17

Introduction/Aim: Advanced-stage classical Hodgkin lymphoma (AScHL) is a therapeutic challenge due to chemoresistance. This study aims to present real-world data on the application of the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) in patients with AScHL.

Methods: This retrospective study examines the clinical and laboratory parameters, as well as the treatment and outcome of patients diagnosed with AScHL, in the period between 2016 and 2020.

Results: The cohort consisted of 49 patients with AScHL. Median follow-up was 47 months (range: 1 – 79). The most important clinical and laboratory characteristics are summarized in Table 1.

All patients were initially treated with ABVD. The overall response rate was 72.3% (complete response = 61.7%; partial response = 10.6%), while 27.7% of patients exhibited refractoriness. Additionally, 10.6% relapsed at a later stage. Of the investigated parameters (Table 1), only an elevated erythrocyte sedimentation rate (ESR) ≥ 50 mm in the first hour) was associated with shorter progression-free survival (PFS), (median PFS = 19 months vs. not reached (NR), in patients with ESR < 50 mm in the first hour; p = 0.039), while the presence of bulky disease was associated with shorter overall survival (OS), (p = 0.044). Also, refractory patients had significantly shorter OS (median OS = 54 months vs. NR in patients who achieved remission; p = 0.004). The median PFS and OS were not achieved; four-year PFS and OS were 61% and 89%, respectively. Patients treated with autologous transplantation (AT) in relapsed/refractory disease had a longer PFS (p = 0.02), but not a longer OS. Brentuximab vedotin (BV) was successfully used in 4/14 patients, of whom three patients received it as consolidation treatment after AT.

Conclusion: A significant number of patients with AScHL cannot be cured with ABVD, thus more intensive treatment or innovative therapies are warranted.

ANEMIA AND HEART FAILURE

Zorica Cvetković — 2024-08-31

The presence of anemia in patients with heart failure is a significant independent adverse prognostic factor. The etiology of anemia is multifactorial and the nature of heart failure itself, advanced age, and frequent comorbidities contribute to its development. Notably, absolute or functional iron deficiency, even in the absence of anemia, significantly diminishes the quality of life, increases hospitalization frequency, and raises mortality rates in patients with heart failure. The intricate etiology and pathophysiology of anemia present a challenge for the accurate interpretation of laboratory parameters of iron metabolism and necessitate a tailored therapeutic approach.

DRUG-INDUCED THROMBOCYTOPENIA

Nada Suvajdžić-Vuković — 2024-09-03

Drugs could cause thrombocytopenia, mostly in hospitalized patients. The incidence of this adverse reaction to medicines is around 10/1,000,000 inhabitants/year. Depending on the pathophysiological mechanism, drug-induced thrombocytopenia can be classified into immune and non-immune. Drugs such as cytostatics, linezolid, ganciclovir, valacyclovir, aspirin, and vancomycin can induce a non-immune form of thrombocytopenia. They achieve this by exerting direct cytotoxic effects on megakaryocytes and platelets, or through proapoptotic mechanisms that affect platelets. On the other hand, the immune form is caused by drug-specific antibodies, which, in the presence of the drug or its metabolite, bind to platelet antigens, leading to accelerated destruction of platelets. Apart from this classic form of drug-induced immune thrombocytopenia (DITP), which is characterized by the acute onset of severe thrombocytopenia (nadir platelet counts < 20 x 109/L) and bleeding, special forms such as heparin-induced thrombocytopenia (HIT), thrombocytopenia caused by the use of immune checkpoint inhibitors, and vaccine-induced thrombotic thrombocytopenia (VITT) are identified. HIT is the most common DITP in which nadir platelet count is usually around 60x10⁹/L and the clinical presentation is dominated by thrombosis (venous and less often arterial). Conversely, VITT is characterized by the onset of thrombosis and thrombocytopenia between 4 and 30 days after the administration of adenoviral vector vaccines. The mortality in this form of LITP ranges between 25% and 60%.

HEMORRHAGIC COMPLICATIONS ASSOCIATED WITH THE USE OF DIRECT ORAL ANTICOAGULANTS

Nikica Sabljić — 2024-08-31

The milestone of treating and preventing venous thromboembolism (VTE) is the application of anticoagulants. For many years the cornerstone was the use of vitamin K antagonists (VKAs), but it was associated with numerous obstacles and complications. With the introduction of a new generation of direct oral anticoagulants (DOAC), some of the difficulties, such as delayed onset/offset of the action, individual dose modifications, inhibition of several coagulation factors, need for frequent monitoring of prothrombin time, multiple drug interactions, have been overcome, while maintaining an adequate safety profile. Therefore, DOACs have rapidly replaced VKAs as a standard of care in the treatment and prevention of VTE, as well as in the prevention of ischemic complications in patients with non-valvular atrial fibrillation. However, the expected consequence of the use of anticoagulant drugs is increased bleeding risk. Several randomized and retrospective studies have analyzed the risk of bleeding associated with the use of DOACs compared to VKAs and between DOACs. It has been clearly shown that intracranial hemorrhage risk is decreased with DOAC compared to VKA, while most studies have shown that the risk of major bleeding is the same or even lower with DOAC. Considering DOAC's efficacy, excellent safety, and simple application compared with VKAs, it does not surprise their increasingly frequent application in everyday clinical practice. Will VKAs gradually become a part of history, or will their use be limited to a specific, clearly defined population? The time has to show.

TREATMENT OF PRIMARY MYELOFIBROSIS, WHERE WE STAND TODAY?

Andrija Bogdanović — 2024-09-04

Introduction: Primary myelofibrosis (PMF) is a clonal hematopoietic neoplastic disease characterized by constitutive complaints, splenomegaly, anemia and very often thrombocytopenia.

Aim: To analyze and compare data from clinical trials, focusing on both current and emerging therapeutics.

Methods: The analysis of published clinical trials and relevant papers.

Results: Currently, the gold standard for treating primary myelofibrosis (PMF) is ruxolitinib, the first-in-class JAK inhibitor (JAKi). It has achieved a ≥35% reduction in spleen volume (SVR) in 41.9% of patients compared to placebo and has led to a >50% improvement in symptoms, as measured by the Total Symptom Score (TSS), in 49.5% of treated individuals. Ruxolitinib is not an ideal drug, as some patients experience worsening anemia, thrombocytopenia, and an increased susceptibility to various infections. Some patients are required to discontinue the treatment or reduce the dosage. Another approved JAK inhibitor, fedratinib, has shown promising results as a second-line treatment following ruxolitinib failure. As a first-line therapy, fedratinib achieved a spleen volume reduction (SVR) of ≥35% in 47% of patients, with a >50% improvement in TSS in 40% of cases.

In transfusion-dependent patients, momelotinib has demonstrated good results, showing non-inferiority to ruxolitinib, with similar spleen volume reduction (SVR≥35%) rates of 26.5% compared to 29% with ruxolitinib. Momelotinib treatment reduced transfusion independence by 17% compared to ruxolitinib (66% vs 49%). In thrombocytopenic patients (Plt 50-100 x10⁹/L), pacritinib is the newest therapy; it reduces spleen volume compared to adjusted ruxolitinib dosing without worsening thrombocytopenia.

Drugs combined with ruxolitinib (e.g. navitoklaks, pelabresib) have the purpose to improve the outcome, especially in spleen reduction.

Conclusion: Treating PMF remains a challenge. While ruxolitinib provides effective disease control in nearly half of patients, new therapies are needed to enhance outcomes both overall and in those with refractory disease.

CLINICAL MANIFESTATIONS ASSOCIATED WITH THE PRESENCE OF ANTIPHOSPHOLIPID ANTIBODIES

Predrag Miljić — 2024-09-08

Antiphospholipid antibodies (aPL antibodies) are a heterogeneous group of autoantibodies that target anionic phospholipids or phospholipid-binding proteins. They can be associated with numerous clinical manifestations in almost all areas of clinical medicine, but antiphospholipid syndrome (APS) is the most precisely defined entity. The most common clinical manifestations of aPL are thrombosis in any part of the circulation, as well as pregnancy complications in the form of miscarriage or premature birth due to preeclampsia, eclampsia, or placental insufficiency. According to the modified Sapporo classification of 2006, thrombosis and/or pregnancy complications represent the clinical criteria for diagnosing APS. However, in approximately a quarter of patients with APS, additional clinical manifestations are present, which are not accepted as criteria for APS. Interestingly, these manifestations can be associated with aPL antibodies even in the absence of thrombosis or pregnancy morbidity, i.e., without the presence of the criteria for definitive APS. Recognizing non-criteria manifestations is highly significant because it can draw attention to the possible presence of aPL antibodies and indicate the presence of APS or the risk of its occurrence. The latest classification was published in 2023 by the American College of Rheumatology/European Alliance of Rheumatology Associations (ACR/EULAR). It expanded the list of clinical criteria for the recognition of antiphospholipid syndrome. This classification demonstrates higher specificity but lesser sensitivity in recognizing APS than earlier criteria. At present, the application of the ACR/EULAR criteria is primarily intended for research purposes, i.e., selecting study subjects, rather than for diagnosing APS in everyday clinical practice.

LIGHT CHAIN DEPOSITION DISEASE

Danijela Jovanović — 2024-09-15

Light chain deposition disease is one form of monoclonal immunoglobulin deposition disease. In terms of frequency, it is a rare entity that occurs in middle-aged people, more often males. It most often affects the kidneys, with a clinical picture of nephritic syndrome, but it can also be localized in other organs, such as the liver, lungs, heart, gastrointestinal tract, skin, and others. The symptoms and signs of the affected organ dominate the clinical picture. The diagnosis is most often established by biopsy of the affected organ, whereby Congo red staining differentiates it from light chain amyloidosis, and then bone marrow evaluation is performed to rule out other plasmacytic dyscrasias. Therapy is based on therapeutic modalities for treating multiple myeloma, including proteasome inhibitors (bortezomib), autologous hematopoietic stem cell transplantation, and transplantation of the affected organs if there has been a complete loss of function. Data on monoclonal antibody therapy (daratumumab) opens up new therapeutic possibilities for the treatment of this disease. Diagnosis and treatment of this disease require a multidisciplinary approach, primarily by nephrologists, hematologists, and pathologists.

FERROPTOSIS AND ITS CLINICAL SIGNIFICANCE

Danijela Agić — 2024-09-25

Introduction: Ferroptosis, mentioned as such for the first time in 2012 by Dixon et al., is an iron-dependent type of cell death that occurs in the presence of lipid peroxides. The mechanism of the process and the signaling pathways involved in it differ from the previously known apoptosis, necrosis, and autophagy. An inflammatory reaction also occurs, which further distinguishes this type of cell death from apoptosis. Ferrostatin inhibits this process.

Methods: A review of the literature obtained by searching the Medline database was performed, with a special focus on studies concerned with the importance of ferroptosis in clinical medicine, primarily hematology.

Results: Iron metabolism in malignant and healthy cells differs. Malignant cells tolerate oxidative stress well and avoid ferroptosis. According to literature data, various tested agents stimulate ferroptosis and thus become possible therapeutic agents. Some genes linked to iron metabolism have shown prognostic significance in patients with diffuse large B-cell lymphoma.

Conclusion: The discovery of new mechanisms of cell death and the signaling pathways involved in this process leads to potentially new target therapy. Although promising, these results require validation through further research.

HODGKIN’S LYMPHOMA IN PREGNANCY: CASE REPORT AND REVIEW OF LITERATURE

Jelena Ivanović — 2024-08-31

Introduction/Objective: The incidence of Hodgkin lymphoma (HL) is high during the reproductive years, making the occurrence of this malignancy during pregnancy a significant issue in everyday clinical practice. The aim is to present a case study demonstrating the characteristics of clinical courses and analyze published data through a literature review.

Case report: A 33-year-old pregnant woman in her third trimester developed neck swelling, night sweats, itching, and weight loss. Ultrasound examination revealed significant lymphadenopathy in the supraclavicular region. Surgical excision of the lymph node and pathological verification confirmed the diagnosis of Hodgkin lymphoma. Given the pregnancy and the limited use of radiographic diagnostics, magnetic resonance imaging (MR) was performed and confirmed generalized lymphadenopathy with resultant hydronephrosis of the right kidney. After diagnosing advanced-stage HL, it was decided to initiate specific hematologic treatment with chemotherapy. Delivery was carried out at 37 weeks of gestation via vaginal delivery, with no complications for the mother or newborn. Following delivery, a complete disease reevaluation was conducted, and it was decided to continue treatment with a total of six cycles of chemotherapy according to the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) protocol. After six cycles of chemotherapy, metabolic remission of the disease was achieved.

Conclusion: Managing Hodgkin lymphoma during pregnancy presents a complex challenge requiring a coordinated multidisciplinary approach and a personalized treatment plan.

MULTIPLE MYELOMA WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT – CASE SERIES

Andrijana Kojić — 2024-09-09

Introduction: Central nervous system involvement in multiple myeloma (CNS-MM) is a very rare entity accounting for less than 1% of all extramedullary multiple myeloma, which manifests as a variety of neurological deficits. Treatment modalities can be locally administered therapy, including intrathecal chemotherapy and radiotherapy, as well as systemic therapy, including autologous/allogeneic hematopoietic stem cell transplantation (AHSCT).

The aim: This article aims to present the experience of our center in the treatment of this rare entity.

Case reports: The first patient was diagnosed with multiple myeloma BJ lambda CS IIIA R-ISS 2 with a tumor mass located at the base of the skull, causing right facial nerve paralysis. The patient underwent six treatment cycles of the CVD (cyclophosphamide, bortezomib, dexamethasone) regimen, achieving partial remission, followed by palliative radiation and autologous stem cell transplantation. The treatment was continued with the DaraRd (daratumumab, lenalidomide, dexamethasone) regimen aimed at a second stem cell transplant which is to be carried out upon deepening remission. The overall survival of the patient, so far, is 20 months. The second patient with multiple myeloma BJ kappa CS IIIA ISS 2 developed CNS involvement with the first recurrence of the disease. Cranial radiation and seven cycles of the PAD (bortezomib, doxorubicin, dexamethasone) regimen were carried out, leading to disease progression and death. The overall survival of the patient was 48 months, with 25 months survival since the diagnosis of CNS infiltration.

Conclusion: Despite advances in diagnosis and treatment, the prognosis for CNS-MM remains poor because of its complex and aggressive clinical behavior. Due to its low incidence, available data are limited indicating the need for further studies involving this small group of patients.

DISEASE PROGRESSION IN PATIENTS WITH LOW-RISK PRIMARY MYELOFIBROSIS – CASE REPORT

Mihailo Smiljanić — 2024-09-09

Introduction: The median survival (OS) of patients with low-risk PMF is over 15 years, but according to the "MOST" prospective study, disease progression occurs in almost 60% of these patients.

Aim: to present the disease course and treatment outcome of patients with low-risk PMF.

Case report: All patients were diagnosed with PMF, low-risk IPSS, and normal initial cytogenetics.

Case 1: A 61-year-old male patient was admitted in May 2016 with Tr 772x10⁹/L, LDH 566 U/L, no splenomegaly, JAK2V617F+. He was initially treated with hydroxyurea (HU) from 2016 to 2020. In 2021, he was introduced to ruxolitinib due to the development of splenomegaly and leukocytosis, with disease progression 18 months later (spleen 26 cm, Plt 20x10⁹/L, 10% blasts in the marrow, complex karyotype: -5, del 7q, mar+). Azacitidine was introduced, but death occurred due to sepsis in October 2022. OS is 66 months.

Case 2: A 47-year-old female patient was admitted in July 2011 with Tr 899x10⁹/L, LDH 899 U/L, spleen 15x7 cm, JAk2V617F+, and ASXL+. She was initially treated with HU and has been treated with ruxolitinib since October 2013 due to the progression of splenomegaly (spleen 19.3 cm, LDH 1881 U/L), with subsequent normalization of spleen size, number of Tr, and LDH. The patient is in remission. OS is 126 months.

Case 3: A 64-year-old male patient was admitted in May 2012 with Tr 1457x10⁹/L, LDH 631 U/L, borderline splenomegaly, JAk2V617F-, MPL+, SRSF2+, U2AF1+, ASXL1+. He was initially treated with HU (May 2012) and since April 2019 with danazol due to the emergence of transfusion dependence. Due to heart failure, death occurred in February 2020. OS is 96 months.

Conclusion: Some patients with low-risk PMF have disease progression, and future studies will show whether early NGS analysis of non-driver mutations and early initiation of therapy contribute to changing the course of the disease.