Rudžianskienė, Milda

Background and Objectives CMV infection remains a common and clinically significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the setting of profound post-transplant immunosuppression. CMV reactivation occurs frequently in the early post-transplant period and represents a major challenge in clinical management, especially among seropositive recipients. It may contribute not only to direct organ involvement but also to indirect effects, including increased susceptibility to secondary infections and impaired immune reconstitution. The clinical impact of CMV reactivation may vary depending on patient-related and transplantrelated factors, reflecting the heterogeneity of the transplanted population. Despite advances in viral monitoring and preemptive therapy, CMV reactivation continues to be associated with an increased risk of post-transplant complications and higher mortality rates. This study aimed to assess the frequency of CMV reactivation and evaluate its impact on complications and early post-transplant mortality in a retrospective single-center cohort. Material and Method A retrospective single-center study was conducted including 77 patients who underwent allogeneic hematopoietic stem cell transplantation at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics between 2020 and 2025. The study population consisted of adult patients with a median age of 56 years, with a balanced sex distribution, and predominantly myeloid underlying diseases. CMV reactivation was monitored using quantitative polymerase chain reaction. Associations between CMV reactivation and post-transplant complications as well as early posttransplant mortality were analyzed using appropriate statistical methods, including chisquare or Fisher’s exact test for categorical variables and non-parametric tests for continuous variables. Early mortality was defined as death during the initial posttransplant hospitalization or within 100 days after transplantation, whichever occurred later. Multivariate logistic regression analysis was performed to identify independent risk factors. IBM SPSS Statistics (version 30.0.0) was used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results CMV reactivation was observed in 53.2% of patients and occurred in 58.0% of seropositive recipients with available serostatus data. The median time to CMV reactivation was 14 days after transplantation (IQR 7.5–27.5), with a mean of 17.8 ± 12.0 days. Antiviral treatment for CMV infection was required in 43.9% of patients with reactivation, reflecting a substantial clinical burden of CMV management after transplantation. CMV reactivation was more frequently observed in patients who developed graft-versus-host disease (65.0% vs. 49.1%), although this difference did not reach statistical significance. Patients with CMV reactivation had a higher frequency of infectious complications (70.7% vs. 55.6%) and overall complications (85.4% vs. 72.2%) compared to those without reactivation; however, these associations did not reach statistical significance. A similar trend was observed across different complication types, suggesting a consistent pattern despite the lack of statistical significance. No significant association was found between CMV DNA load and the number of complications; however, this finding should be interpreted with caution given the limited sample size. CMV reactivation was associated with significantly increased early post-transplant mortality (36.6% vs. 11.1%; p = 0.010), indicating a clinically meaningful impact on early outcomes. In multivariate analysis adjusted for age and graft-versus-host disease, CMV reactivation remained an independent predictor of early mortality (OR = 5.00; 95% CI: 1.44–17.39; p = 0.011). These findings highlight the clinical relevance of CMV reactivation in the early post-transplant period. Conclusions and Recommendations CMV reactivation is a frequent complication after allo-HSCT and was associated with significantly increased early post-transplant mortality, remaining an independent predictor after adjustment for relevant clinical factors. A consistent trend towards higher rates of infectious and overall complications was observed in patients with CMV reactivation, although statistical significance was not reached. In contrast to findings reported in the literature, no association was identified between CMV DNA load and complication burden, which is likely related to the limited sample size of this study. The relatively small cohort (n = 77) may have reduced the statistical power to detect significant associations. These findings highlight the importance of careful CMV monitoring and timely antiviral intervention in the early post-transplant period. Further studies with larger cohorts are needed to better define the clinical impact of CMV reactivation and to validate these findings.

Objectives: The aim of this study was to assess the impact of polymorphisms in cytokine genes on pain severity and pain treatment with palliative radiotherapy.

Background: Cytomegalovirus (CMV) infection/reactivation continues to represent one of the most opportunistic infections after haematopoietic stem cell transplantation (HSCT). CMV infection can escalate to CMV disease with complex outcomes that may be challenging to manage. CMV can indirectly contribute to reduced overall survival (OS) and increase non–relapse mortality (NRM) in HSCT patients. Prevention of CMV and early pre–emptive strategies are fundamental to reduce the risk of end–organ disease. Risk factors for CMV infection or disease include CMV seropositive recipients, mismatched and unrelated transplants, the use of T cell depletion agents, steroid therapy, graft–versus–host disease (GvHD), administration of CMV–positive blood products in seronegative recipients, among other factors. Ganciclovir or valganciclovir remain the mainstream of CMV management in HSCT. Due to adverse effects such as leukopenia and nephrotoxicity, some patients may exhibit intolerance or necessitate early discontinuation of such drugs. A recent review indicated that the pre–emptive use of CMVIG resulted in an overall response in 65%–100% of patients with a clearance time of 14 to 21 days (Whittaker et al 2023). Methods: Objectives: To assess the efficacy of CMVIG in the early pre–emptive management of CMV in high–risk HSCT recipients. Methods: Between December 2022 and October 2024, 13 high–risk patients’ post–prophylaxis with early detection of CMV reactivation were treated with CMVIG. All patients were managed with CMVIG as monotherapy. Clinical parameters such as viral load (IU/ml), medication side effects, and patient tolerance were systemically evaluated. Results: All patients experiencing CMV reactivation exhibited at least one–risk factor predisposing them to CMV reactivation, including D + /R+ serostatus, exposure to anti–thymocyte globulin (ATG), or received a matched unrelated donor (MUD) or haploidentical donor. All patients were receiving Valacyclovir 500 mg b.i.d. for prophylaxis. The median age at transplantation was 53.8 years (range: 24–69). The median viremia level detected during treatment was 3175 IU/ml. (1300 IU/ml. min; 7000 IU/ml. max) with no clinical symptoms. A favourable response defined as achieving undetectable CMV viral load was achieved in all patients. None of the patients required additional antiviral therapy following early initiation of CMVIG. The median duration to achieve viral response was 20 days with CMV load monitoring 2 times per week. CMVIG was well tolerated among all patients, with no reported adverse reactions recorded. Conclusions: This single–centre experience demonstrates the clinical efficacy of CMVIG as monotherapy in the early pre–emptive management of CMV infection, achieving complete remission of in all patients with no product related side effects recorded. CMVIG may be considered as a suitable option in the pre–emptive management to enhance virus clearance, and to avoid or shorten the need for antiviral therapy in high–risk patients or in patients presenting with intolerance to antiviral drugs

Background: Malnutrition is a common condition in cancer patients, especially those with hemato–oncological diseases, and is a direct consequence of both the disease itself and its treatment. In patients undergoing hematopoietic stem cell transplantation (HSCT), the type of conditioning regimen, the nature of the transplant (autologous vs. allogeneic), and post–transplant complications can significantly affect nutritional status. Conditioning regimens often cause side effects such as mucositis, nausea, vomiting, diarrhea, fever, and infections, which impair food intake, contribute to weight loss, and increase the risk of sarcopenia, affecting 20–70% of patients depending on the type of tumor. Malnutrition is responsible for approximately 10–20% of cancer–related deaths. Therefore, integrating routine malnutrition assessment into clinical care is essential for improving patient outcomes. Methods: A retrospective analysis was conducted using medical records of 120 patients treated at the Hospital of LUHS KC between January 2022 and August 2024. The inclusion criteria were patients who underwent either autologous or allogeneic hematopoietic stem cell transplantation (HSCT). Malnutrition was identified according to the ESPEN guidelines on nutrition in cancer patients, and patients were considered malnourished if parenteral feeding was indicated based on these guidelines. Statistical significance was considered at p < 0.05. Results: Out of 120 patients, 91 (75.8%) underwent autologous HSCT and 29 (24.2%) allogeneic HSCT. Patients receiving allogeneic HSCT had significantly higher rates of malnutrition (55.9%, p < 0.001). The most used conditioning regimen for autologous HSCT was melphalan (76.9%), while reduced–intensity conditioning (RIC) protocols were most common for allogeneic HSCT (37.9%). No significant association was found between conditioning regimens and malnutrition. However, there were significant changes in albumin, protein, and hemoglobin (Hgb) levels before and after HSCT (p < 0.001). Univariate regression analysis showed that higher protein levels before autologous HSCT (OR 0.845, 95%CI 0.743–0.961, p = 0.010) and higher albumin levels after autologous HSCT (OR 0.819, 95%CI 0.685–0.978, p = 0.027) were associated with a reduced risk of malnutrition. Similarly, higher Hgb levels before allogeneic HSCT (OR 0.910, 95%CI 0.834–0.992, p = 0.032) and higher protein levels after allogeneic HSCT (OR 0.724, 95%CI 0.546–0.960, p = 0.025) were also linked to a reduced risk of malnutrition. Conclusions: Patients undergoing allogeneic HSCT were more likely to experience malnutrition. Pre–HSCT nutritional support was found to have a significant impact on nutritional outcomes post–transplant. Additionally, monitoring and timely correction of laboratory parameters such as albumin, protein, and hemoglobin levels can help mitigate the risk of malnutrition.

Background and Objectives Autologous stem cell transplantation (autoSCT) is a cornerstone in the treatment of various haematological malignancies, such as multiple myeloma (MM), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). By allowing for high-dose chemotherapy administration followed by haematopoietic stem cell (HSC) rescue, autoSCT significantly improves progression-free and overall survival rates in afflicted patients. This highlights the critical role of HSC mobilization in autoSCT, since yielding a sufficient number of HSCs is vital for transplantation success. However, a subset of patients fails to reach this threshold, resulting in unsuccessful autoSCT. Analyzing the major predictive factors influencing HSC transplantation, can provide valuable insights into the enhancement of mobilization protocols and the optimization of patient outcomes. Therefore, the establishment of distinct predictive factors is key for tailoring effective mobilization strategies. To address this challenge, this study aimed to identify the patient-specific, disease-specific and treatment-specific factors influencing HSC mobilization in patients with malignant diseases undergoing autoSCT, thereby contributing to clinical advancements in mobilization strategies. The assessed parameters consisted of age, gender, comorbidity count, prior radiotherapy, diagnosis, bone marrow plasma-cell infiltration percentage and induction therapy regimens. The objectives for this study were:

1. Investigate patient-specific factors influencing HSC mobilization in autoSCT in patients with malignant hematological diseases.
2. Evaluate disease-specific variables affecting HSC mobilization in autoSCT in patients with malignant diseases.
3. Analyze treatment-related factors predicting HSC mobilization in autoSCT in patients with malignant hematological disorders. Material A retrospective observational cohort study was conducted at the Department of Haematology at the Lithuanian University of Health Sciences Kaunas Clinics. Data from 154 patients diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM) were collected from institutional database between 2020 and 2024. The primary outcome variable was the absolute yield of CD34⁺ (i.e., a specific marker for HSCs), cells expressed in ×10⁶ cells/kg. Results The analysis of CD34+ cell yields indicated that mobilization protocols were successful across the cohort, confirming sufficient collection of CD34+ cells for effective autoSCT. The majority of patients achieved CD34+ cell yields well above the minimum threshold of 2 ×10⁶ cells/kg, with only one patient below this range. This highlights the overall efficacy of the applied mobilization strategies, despite the presence of factors known to adversely influence mobilization outcomes. The findings of the study identified age, prior radiotherapy, diagnosis, and certain induction therapies as significant statistical predictors of HSC mobilization outcomes (p-value < 0,05). Two patient-related factors – age and prior radiotherapy – showed a statistically significant negative correlation with CD34⁺ cell yield, as indicated by their respective p-values of 0,0000067 and 0,012. Regarding disease-specific factors, Hodgkin lymphoma (C81.0, p-value = 0,000067), and aggressive T-cell lymphoma (C84.0, p-value = 0,047) demonstrated the strongest association with HSC mobilization – yielding significantly fewer CD34⁺ cells in comparison with other diagnoses. Finally, certain induction therapies – as treatment-related factors – played a pivotal role in mobilization outcomes. DHAP (p-value = 0,0026), MTX-R (p-value = 0,0000047), and Vel-Dex (p-value = 0,023) demonstrated a statistically significant favorable effect on CD34⁺ cell yields. Contrastingly, ICE had a statistically significant negative correlation with CD34⁺ cell yield, with a p-value of 0,021. Conclusions It was concluded that HSC mobilization is a multifactorial process encompassed by specific patient-related, disease-related, and treatment-related factors. The results support the implementation of individualized, patient-centered mobilization strategies. Practical recommendations involve early risk assessment, integration of enhanced mobilization regimens for high-risk patients, and diligent selection of induction therapies in order to optimize mobilization outcomes.

Introduction Cardiac myeloid sarcoma occurs less than <1% of all sarcoma cases. For this reason, the literature data is limited to case reports and small retrospective studies. Clinical knowledge of this condition, its manifestations and treatment are limited. Case Presentation A 68-year-old man presented typical symptoms of unstable angina pectoris (pain in the chest area, shortness of breath, general weakness). Echocardioscopy revealed a 26-32 mm tumor in right atrial cavity. Cardiac magnetic resonance imaging (MRI) revealed solid, heterogenic, contrast-accumulating tumorous structure (87x72x74 mm) with solid and necrotic areas on the right side of the heart. Even though the endocardium biopsy results did not show any tumorous changes, tumor excision surgery and histological verification revealed an acute myeloid leukemia (AML). Histological testing confirmed myeloid sarcoma (most probably AML infiltration): polymorphic cells with big, uneven nucleus, multiple mitoses, positive LCA, CD117, CD99, CD34, bcl-2 marks, Proliferation Ki67 index was 80%. For further diagnosis, bone marrow aspiration and blood smear were taken. Both showed blasts numbers 5% and 7%. Genetic testing showed CBFB-MYH11 inv(16)(p13;q22) mutation, which is typical for AML. Patient underwent treatment with induction: Daunorubicin and Cytarabine (7+3), consolidation with high dose Cytarabine (3 courses), allogenic matched unrelated identical donor haemopoetic stem cells transplantation. Complete remission was achieved. Discussion The most common symptom of cardiac myeloid sarcoma is pericarditis, with or without leukaemic cells in the pericardial fluid. Other clinical signs may include tachycardia, chest tightness, palpitations, chest pain, arrhythmias. The diagnostic gold standard is MRI and biopsy, in some of the described clinical cases PET/CT has been used, due to the more precise location of the biopsy. Treatment is given according to the standard AML protocol. Conclusions Cardiac myeloid sarcoma is treated according to the algorithms of AML. Systemic chemotherapy and allogeneic haematopoietic stem cell transplantation significantly prolong overall survival. Patient follow-up in the posttransplantation period is important for possible recurrence of the disease or post-transplant complications. [1–4]

Background: Hematopoietic stem cell transplantation (HSCT) can cause cardiac toxicity of different grade. In this study we aimed to evaluate the impact of mobilization procedure for autologous HSCT process on left and right ventricle sizes and systolic function. Methods: Data of 35 patients undergoing autologous HSCT at the Department of Oncology and Hematology in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from October 2021 till Feb 2023 were analyzed. Bioethics approvement for prospective study was obtained (No BE-2-96). HSCT was performed for various reasons – mostly multiple myeloma, also mantle cell lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma, Ewing sarcoma. All patients underwent hematopoietic stem cell mobilization with chemotherapy and filgrastim 10 µg/kg/d. Echocardiography was performed before enrolling to the transplantation process and after mobilization before the conditioning regimen. Left ventricular end diastolic diameter (LVEDD), LVEDD index according to body surface area (BSA) (LVEDDi), left ventricular ejection fraction (LV EF), left ventricular global longitudinal strain (GLS), right ventricle (RV) end diastolic diameter (RVEDD, tricuspid annular systolic velocity (S’) using tissue doppler and tricuspid annular plane systolic excursion (TAPSE) were measured before and after mobilization and compared. Statistical analysis was performed using SPSS statistics 20. Qualitative data is presented as an absolute value (N) and percentage (%), quantitative parameters are given as average (m ± standard deviation). We used paired- samples T test to compare quantitative parameters. Statistically significant difference was considered when p<0.05. Results: Out of 35 patients there were 18 men (51,4%) and 17 women (48,6%). Mean age was 57,4±13,15 years, ranging from 18 to 74. 26 (74,3%) patients had multiple myeloma, 4 (11,4%) mantle cell lymphoma, 2 (5,7%) Hodgkin ‘s lymphoma, 2 (5,7%) PCNS diffuse large B cell lymphoma, 1 (2,9%) Ewing sarcoma. Statistically significant difference was observed in the change of RV function. S‘ and TAPSE slightly decreased. Changes of echocardiographic parameters are presented in Table 1. Conclusions: Mobilization procedure in patients undergoing autologous HSCT is associated with reduced RV systolic function. S‘ and TAPSE might be used for early cardiotoxicity evaluation in HSCT patients.

Background: The optimal number of CD34+ cells needed for repetitive autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients remains unclear. As effective novel therapies for MM emerge, the use of salvage autologous hematopoietic stem cell transplantation (auto-HSCT) for relapse/refractory MM is questionable. Methods: We conducted a retrospective single center study using the clinical and laboratory databases. The study included 158 MM patients, 384 apheresis, 536 products and 211 auto-HSCT in the hospital of Lithuanian University of Health Sciences Kaunas Clinics from 2015 to 2022. Peripheral blood hematopoietic stem cells (PBHSC) were harvested after mobilization Cyclo+G-CSF (10 µg/kg) or an additional mobilizing agent such as plerixafor (0.24 mg/kg) if needed. PBHSC harvesting was done via apheresis. In our center the goal is to collect enough CD34+ cells for 3 auto-HSCT, which would equate to at least 10 x106 CD34+/kg. After each apheresis session, CD34+ counts were calculated. If the goal was achieved or if further mobilization was not possible, the harvesting was stopped. We calculated collected cells and divided patients in to 2 groups: A – if the goal is reached, B – goal is not reached. Descriptive statistics were performed on the variables of interest. We report frequencies and percentages as well as mean and ranges where applicable. Results: In total 158 MM patients were mobilized via 384 apheresis, that harvested 536 products, and transplanted at least 1 time. For 100 (63.3%) of the patients the CD34+ goal was achieved (A group), for 58 (36.7%) was not (B group). Mean collected CD34+ cell count for both groups were 12.45 x106/kg (range 2.0 x106 – 31.4 x106 /kg). To reach the CD34+ cell goal, 3 (3%) patients needed only 1 apheresis, most of them 67 (67%) needed 2 procedures, 28 (28%) – 3 apheresis procedures, and 2 (2%) patients needed 4 procedures. In comparison, in the B group more than half of the patients 35 (60.3%) needed 3 or more apheresis procedures. There is a correlation between CD34+ yield and number of apheresis procedures: patients yielding higher CD34+ counts required fewer apheresis procedures compared to those yielding lower CD34+ counts (p<0.01). Out of the patients that reached the targeted CD34+ goal (A group) transplanted in tandem 37 (37%) patients and 5 (5%) received as salvage auto-HSCT. Out of the B group 6 (10.2%) patients received tandem auto-HSCT, but no one received auto-HSCT as salvage. Conclusions: Our analysis evaluated the use of stored cryopreserved PBHSC for a salvage auto-HSCT in patients with MM. We showed that we could collect enough PBHSC for third auto-HSCT in most patients and usually they required 2 or 3 apheresis procedures. A third auto-HSCT was performed in just 5% of the included cohort. The increased survival rates offered by new cellular and immunotherapies, alongside the decreasing frequency of conducting salvage auto-HSCT warrant reconsideration of PBHSC collection goals.

Background and Objectives At the onset of the 21st century, tandem autologous hematopoietic stem cell transplantation (auto-HSCT) demonstrated efficacy in enhancing progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma (MM). Over recent decades, new effective drugs such as immunomodulators, proteasome inhibitors, and monoclonal antibodies have markedly improved treatment outcomes for MM, leading to increased PFS and OS. With the advent of new-generation drugs, the benefit of tandem auto-HSCT in the treatment of patients with newly diagnosed MM has become debatable. This study aimed to assess changes in stringent complete response (sCR) rates following the first and second auto-HSCT, as well as to evaluate the PFS and OS in relation to achieved sCR after tandem auto-HSCT. [...].

Background and Objectives Cytomegalovirus (CMV) infection remains a prevalent and an important challenge encountered post haematopoietic stem cell transplantation (HSCT) (1). If left unaddressed, CMV infection can escalate to CMV disease with adverse outcomes. Additionally, CMV infection alone can indirectly contribute to reduced overall survival (OS) and increased non-relapse mortality (NRM) (2). Prevention serves as the cornerstone for managing CMV infection, while early pre-emptive strategies are employed to mitigate the risk of end-organ disease. Risk factors for CMV infection or disease include CMV seropositive recipients, mismatched and unrelated transplants, the use of T cell depletion agents, steroid therapy, graft-versus-host disease (GvHD), administration of CMV-positive blood products in seronegative recipients, among the other factors. Valganciclovir or ganciclovir remain the mainstream of CMV management in HSCT; however, due to adverse effects such as leukopenia and nephrotoxicity, some patients may exhibit intolerance to these medications or necessitate early discontinuation. Recent survey from the European Society for Blood and Marrow Transplantation (EBMT) highlight the inclusion of CMV immunoglobulin (CMVIG) as a therapeutic option for prophylaxis or pre-emptive interventions (3). The objective was to assess the efficacy of CMVIG in managing early CMV reactivation among high-risk HSCT recipients. [...].