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Simple Summary: Our research explores the profile and risk factors for infections in multiple myeloma patients undergoing treatment with daratumumab, a key drug in chemotherapy regimens for this disease. The study seeks to identify which patients are at the highest risk of developing severe infections and the factors contributing to this risk, as infections are a major concern for these patients. Analysis of patient data from our facility showed that lower hemoglobin levels and poorer performance status significantly increase the risk of serious infections. Additionally, we developed predictive algorithms to identify individuals at elevated risk of developing pneumonia during treatment. The findings from our study may help healthcare providers identify high-risk patients and implement targeted strategies to prevent infections, ultimately improving patient care. Background: Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-based treatment. In this study, we aimed to determine the profile of ICs in MM patients treated with Dara-based regimens and establish predictors of their occurrence. Methods: This retrospective, real-life study included MM patients treated with Dara-based regimens between July 2019 and March 2024 at our institution. Infectious events were evaluated using the Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study group consisted of a total of 139 patients, including 49 NDMM and 90 RRMM. In the RR setting, the majority (60.0%) of patients received the Dara, bortezomib, and dexamethasone (DVd) regimen, whereas ND patients were predominantly (98%) treated with the Dara, bortezomib, thalidomide, and dexamethasone (DVTd) regimen. Overall, 55 patients (39.6%) experienced ICs. The most common IC was pneumonia (37.5%), followed by upper respiratory tract infections (26.8%). Finally, twenty-five patients had severe ICs (grade ≥ 3) and required hospitalization, and eight patients died due to ICs. In the final multivariable model adjusted for setting (ND/RR) and age, hemoglobin level (OR 0.77, 95% CI: 0.61–0.96, p = 0.0037), and Eastern Cooperative Oncology Group (ECOG) >1 (OR 4.46, 95% CI: 1.63–12.26, p = 0.0037) were significant factors influencing severe IC occurrence. Additionally, we developed predictive models using the J48 decision tree, gradient boosting, and random forest algorithms. After conducting 10-fold cross-validation, these models demonstrated strong performance in predicting the occurrence of pneumonia during treatment with daratumumab-based regimens. Conclusions: Simple clinical and laboratory assessments, including hemoglobin level and ECOG scale, can be valuable in identifying patients vulnerable to infections during Dara-based regimens, facilitating personalized prophylactic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) preceded by high-dose chemotherapy is a mainstay in relapsed/refractory lymphoma. The study aimed to compare the efficacy and adverse event profile between BEAM and Benda-EAM (BeEAM) regimens and to evaluate prognostic factors for survival in lymphoma patients undergoing auto-HSCT. Material and methods: We present a single-center retrospective analysis of 82 lymphoma patients (median age 52; IQR 38.2-62.2) who received BEAM (47.6%) or BeEAM (52.4%) followed by auto-HSCT between January 2015 and December 2021. Results: During the post-HSCT period 58% of patients experienced febrile neutropenia (51.3% vs. 64.3% in BEAM and BeEAM, respectively; p = 0.27), 80.5% mucositis (69.2% vs. 90.7%; p = 0.02), 42.5% bacteremia (50% vs. 35.7%; p = 0.26), and 18.8% pneumonia (31.6% vs. 7.1%; p = 0.01). Patients who received bendamustine required more platelet transfusions (p = 0.02). In the multivariate Cox regression model, C-reactive protein level on the first day of hospitalization (hazard ratio - HR = 1.03, 95% CI: 1.01-1.06) and days of agranulocytosis (HR = 1.15, 95% CI: 1.00-1.32) were predictors of poorer overall survival (OS), whereas hemoglobin level at the auto-HSCT was a protective factor in terms of OS (HR = 0.43, 95% CI: 0.23-0.78) and progression-free survival (PFS) (HR = 0.66, 95% CI: 0.45-0.96). The median OS since auto-HSCT was 87 months, while the median PFS was 49 months. No differences in PFS and OS between BEAM and BeEAM regimens were proven. Conclusions: Conditioning with BEAM and BeEAM regimens is associated with comparable post-transplant outcomes. The toxicity of these regimens is comparable; however, BEAM is associated with a higher risk of pneumonia, while BeEAM is associated with a higher risk of mucositis. [ABSTRACT FROM AUTHOR]

Feeding disorders of infancy are common in paediatric practice. Among rare causes of this disturbance is diabetes insipidus (DI), which is a clinical syndrome characterized by polyuria, polydypsia and dehydration with hypernatraemia. Central diabetes insipidus (CDI, vasopressin deficiency) is more common in children than nephrogenic diabetes insipidus (NDI, an inability to respond adequately to vasopressin). Regardless of the type of DI, the main goal of treatment is to decrease thirst and urine output and achieve proper ion and fluid balance. We present three cases of infants with feeding difficulties. The first two cases concerned patients with semilobar holoprosencephaly (HPE). Their stories show the importance of knowing the most common abnormalities associated with HPE, such as CDI. The third child had similar problems with feeding which resembled a defect of the central nervous system, but was finally diagnosed as NDI. The diagnostic and therapeutic approach is demonstrated in the paper with special regards to safe management of hypernatraemic dehydration. [ABSTRACT FROM AUTHOR]

Infectious complications of autologous hematopoietic stem cell transplantation (AHSCT) are the most common adverse effects of the therapy, resulting in prolonged hospitalization and deterioration of patient well‐being. Identifying predictors of these complications is essential for improving patient outcomes and guiding clinical management. This study aimed to examine thrombospondin‐1 (THBS‐1) serum levels as a potential biomarker for predicting bacteremia in AHSCT recipients. Blood samples were collected from 30 patients undergoing BeEAM/BEAM (bendamustine/carmustine, etoposide, cytarabine, melphalan) conditioning regimen at subsequent time points during AHSCT. THBS‐1 levels were quantified using ELISA kits. Patients who developed bacteremia (n = 11) during the AHSCT course had lower THBS‐1 concentration compared with those without (n = 19) (22.88 ± 11.53 µg/mL vs. 15.24 ± 5.62 µg/mL, p =.0325). The ROC curve analysis revealed that THBS‐1 serum concentration at the first day of BeEAM/BEAM regimen had an area under the curve of 0.732 (95%CI: 0.5390.925, p =.0186) with an optimal cut‐off value of 16.5 µg/ml resulting in 82% Sensitivity and 53% Specificity for predicting bacteremia with a median of 11 days before its occurrence. Patients with lower THBS‐1 concentrations experienced febrile neutropenia significantly earlier, with a median difference of 5 days (p =.0037). Patients with a low concentration of THBS‐1 had a higher risk of bacteremia and a shorter time to febrile neutropenia, indicating its potential value as a complications biomarker. Patients with lower serum THBS‐1 concentrations, indicating an increased risk, may be more suitable for an inpatient AHSCT procedure, where close monitoring and immediate intervention are accessible. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy with autologous stem-cell transplantation (ASCT) remains the standard of care in multiple myeloma (MM) patients. This retrospective study aimed to assess the impact of neutrophil-to-lymphocyte ratio (NLR) and other complete blood count (CBC)-based predictors on PFS and OS of transplant-eligible MM patients. The CBC-based biomarkers were evaluated in a single-center cohort of 176 MM patients at three time points: at the diagnosis, the time of ASCT, and +100 d after ASCT. Univariable and multivariable Cox's regression analyses and Kaplan–Meier estimate were used in statistical analysis. NLR at ASCT (HR 1.15, 95% CI: 1.05–1.26) and hemoglobin at ASCT (HR 0.80, 95% CI: 0.68–0.94) were independent factors influencing PFS. In the model for OS, the only statistically significant factors were NLR at ASCT (HR 1.15, 95% CI: 1.04–1.27), bortezomib administration prior to ASCT (HR 0.52, 95% CI: 0.33–0.83) and age at diagnosis (HR 1.03, 95% CI: 1.00–1.06). NLR at ASCT is an independent predictive factor in MM patients undergoing ASCT. [ABSTRACT FROM AUTHOR]

Introduction: Relapsed/refractory multiple myeloma (RRMM) is a challenging setting for management and treatment. In Poland, a substantial fraction of RRMM patients is currently treated with lenalidomide and dexamethasone (Rd). Establishing predictors of treatment-related complications and poor response is crucial for further optimal therapeutic decision-making. Material and methods: This retrospective study included all patients who received the Rd regimen according to the Ministry of Health's drug reimbursement program (B.54) between January 2017 and December 2021 in the Department of Hematology, Medical University of Lodz, Poland. Results: The study group consisted of 174 patients, and the mean age was 67.3 ± 9.0 years. The majority of patients (63.2%) received the Rd at the first relapse//progression. The median PFS was 12.6 months, and the median OS was 22.3 months. The overall response rate was 64.1%, 12.7% achieved complete response (CR), and 20.4% had a very good partial response (VGPR). In multivariate Cox regression analysis for PFS, ISS 3 (HR 1.8, 95% CI: 1.2-2.7, p = 0.0062) and CR/VGPR after 6. cycle (HR 0.4, 95% CI: 0.2-0.9, p = 0.0222) were independent prognostic factors. Similarly, ISS 3 (HR 2.1, 95% CI: 1.3-3.3, p = 0.0012) was related to poorer OS, whereas CR//VGPR achievement was related to improved OS (HR 0.4, 95% CI: 0.2-0.9, p = 0.0238). The most prevalent adverse events in the study group were serious infections (31.0%), neutropenia (28.7%), thrombocytopenia (18.4%), anemia (18.1%) and thromboembolic events (11.5%). In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95% CI: 1.6-11.2, p = 0.0039), ASCT before Rd (OR 2.6, 95% CI: 1.0-6.7, p = 0.048) and anemia (OR 5.0, 95% CI: 1.8-14.0, p = 0.002) were independent factors related to the occurrence of serious infections. Conclusions: RRMM patients with ISS 3 and who did not achieve CR/VGPR have inferior outcomes following Rd and should be candidates for novel drug administration or enrolled in clinical trials. Patients after ASCT, with hypoalbuminemia or anemia during Rd treatment are at risk of serious infectious complications. [ABSTRACT FROM AUTHOR]

Introduction: More than 28,000 autologous hematopoietic stem-cell transplantations (AHSCTs) are performed annually in Europe. Currently, special attention is given to manageable complications encountered during the procedure. The study aimed to identify the signature of serum miRNAs, which could be used in clinical practice to assess the risk of AHSCT complications. Material and methods: The study group consisted of patients treated with AHSCT at the Department of Hematology and Transplantology, Copernicus Memorial Hospital in Lodz, Poland. Serum samples were taken from each patient at four timepoints: (T1) before conditioning, (T2) on the day of AHSCT (day 0), on day +7 (T3), and +14 day (T4). Patients were divided into two cohorts: exploratory (N1 = 10) in which serum miRNA-seq was performed, and in the second (N2 = 69), 17 selected miRNAs (significant in differential expression analysis between timepoints) were validated using RT-qPCR. The conditioning regimen for MM patients was melphalan 200 mg/m², while in lymphoma patients, BeEAM was used. The patients in the N2 cohort were divided into training (N = 46) and validation set (N = 23). Two neural network models were constructed to predict the occurrence of oral mucositis (OM) and delayed engraftment (DE). Three predictors were included in each model: the regimen used and differentially expressed miRNAs between groups with and without particular complication on T2: miR-375 and miR-223-3p in the OM model; hsa-miR-221-3p and hsa-let-7f-5p in DE model. Results: The model for OM worked equally well on the training (AUC 0.925, 95% CI: 0.853-0.997) and validation set (AUC 0.864, 95% CI: 0.651-0.971). The model for DE prediction reached AUC 0.909, 95% CI: 0.802-1.000 on the training and AUC 0.952, 95% CI: 0.762-0.989 in the validation set. Conclusions: Our data suggest that circulating miRNAs have the potential to develop tools for the prediction of AHSCT complications-OM and DE, enabling improvement of patient management and optimal utilization of health care resources. [ABSTRACT FROM AUTHOR]