MicroRNAs predict early complications of autologous hematopoietic stem cell transplantation.

Autologous hematopoietic stem cell transplantation (AHSCT) remains the most prevalent type of stem cell transplantation. In our study, we investigated the changes in circulating miRNAs in AHSCT recipients and their potential to predict early procedure-related complications. We collected serum samples from 77 patients, including 54 with multiple myeloma, at four key time points: before AHSCT, on the day of transplantation (day 0), and at days + 7 and + 14 post-transplantation. Through serum miRNA-seq analysis, we identified altered expression patterns and miRNAs associated with the AHSCT procedure. Validation using qPCR confirmed deviations in the levels of miRNAs at the beginning of the procedure in patients who subsequently developed bacteremia: hsa-miR-223-3p and hsa-miR-15b-5p exhibited decreased expression, while hsa-miR-126-5p had increased level. Then, a neural network model was constructed to use miRNA levels for the prediction of bacteremia. The model achieved an accuracy of 93.33% (95%CI: 68.05-99.83%), with a sensitivity of 100% (95%CI: 67.81-100.00%) and specificity of 90.91% (95%CI: 58.72-99.77%) in predicting bacteremia with mean of 6.5 ± 3.2 days before occurrence. In addition, we showed unique patterns of miRNA expression in patients experiencing platelet engraftment delay which involved the downregulation of hsa-let-7f-5p and upregulation of hsa-miR-96-5p; and neutrophil engraftment delay which was associated with decreased levels of hsa-miR-125a-5p and hsa-miR-15b-5p. Our findings highlight the significant alterations in serum miRNA levels during AHSCT and suggest the clinical utility of miRNA expression patterns as potential biomarkers that could be harnessed to improve patient outcomes, particularly by predicting the risk of bacteremia during AHSCT.

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)-miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p-in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29-3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11-0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63-0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures.

A low thrombospondin-1 serum concentration is related to increased bacteremia risk in lymphoma patients treated with BeEAM/BEAM conditioning regimen and autologous stem cell transplantation.

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.

High serum miR-223-3p expression level predicts complete response and prolonged overall survival in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation.

Introduction: AHSCT is the treatment of choice for newly diagnosed patients with transplant-eligible multiple myeloma (MM). However, considerable variability in response to autologous hematopoietic stem cell transplantation (AHSCT) results in only 50% of patients achieving complete response (CR) after AHSCT, which is directly associated with improved progression-free and overall survival (OS). In this study, we aimed to investigate the potential predictive role of selected serum miRNAs in MM patients who underwent AHSCT. Patients and methods: Serum expression level of 6 miRNAs: miR-221-3p, miR-15b-5p, miR-223-3p, miR-320c, miR-361-3p, and miR-150-5p was evaluated in 51 patients who underwent AHSCT. Blood samples were collected at two time points: before conditioning chemotherapy (T1) and fourteen days after transplant (+14) (T2). Results: All selected miRNAs significantly changed their expression level across the procedure- two were up-regulated after AHSCT: hsa-miR-320c (FC 1.42, p<0.0001) and hsa-miR-361-3p (FC 1.35, p=0.0168); four were down-regulated: hsa-miR-15b-5p (FC 0.53, p<0.0001), hsa-miR-221-3p (FC 0.78, p=0.0004), hsa-miR-223-3p (FC 0.74, p=0.0015) and hsa-miR-150-5p (FC 0.75, p=0.0080). Notably, before AHSCT, hsa-miR-223-3p was down-regulated in International Staging System (ISS) III patients (FC=0.76, p=0.0155), and hsa-miR-320c was up-regulated (FC=1.27, p=0.0470). These differences became non-significant after AHSCT. Eight (15.69%) patients achieved CR before AHSCT and 17 patients (33.33%) at +100 days after AHSCT. In multivariate logistic regression analysis, achievement of CR after induction and hsa-miR-223-3p at T1 were independent predictors of CR after AHSCT. In multivariate Cox regression analysis, hsa-miR-223-3p at T1 expression level was associated with prolonged OS (HR 0.06, 95%CI: 0.00 - 0.99, p=0.0488). Conclusion: Serum expression of has-miR-223-3p is a predictor of CR and prolonged OS in MM patients undergoing AHSCT.

Neutrophil to lymphocyte ratio (NLR) impact on the progression-free survival and overall survival of multiple myeloma patients treated with high-dose chemotherapy and autologous stem cell transplantation.

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.

An elevated systemic inflammation index is related to an inferior response to pomalidomide and dexamethasone treatment in patients with relapsed and refractory multiple myeloma.

Introduction: The systemic inflammation index (SII) might serve as an indicator of the equilibrium between the inflammatory and immune responses. The aim of the study was to determine the clinical value and prognostic significance of SII in the cohort of multiple myeloma (MM) patients treated with a regimen of pomalidomide and dexamethasone (Pd). Material and methods: This retrospective, real-life study included patients who received a Pd regimen in our centre between November 2018 and July 2022. The systemic inflammation index was calculated from peripheral blood counts of platelets, neutrophils, and lymphocytes collected shortly before commencement of Pd treatment using the equation: SII = N × P/L, where N, P, and L are the respective counts per litre of peripheral blood for neutrophils, platelets, and lymphocytes. Results: The study group consisted of 54 patients. Most patients received Pd as the third (38.9%) or fourth (37.0%) line of treatment. The median number of completed treatment cycles was 5 (IQR: 1-12). The median progression-free survival (PFS) was 6.8 months and overall survival (OS) 14.8 months. High SII (> 374) was an independent prognostic factor for PFS (HR = 3.0, 95% CI: 1.4-6.3, p < 0.01) and OS (HR = 2.2, 95% CI: 1.0-4.6, p = 0.04). In the low SII group, the respective median PFS and OS values were 9.6 and 21.7 months, compared to 2.6 (p = 0.018) and 5.5 months (p = 0.035) in the high SII group. Conclusions: The systemic inflammation index has prognostic significance in MM patients treated with Pd. A high SII predicts a poorer outcome in pretreated MM patients undergoing Pd treatment evaluation. As such, it may well be a key factor for guiding subsequent treatment decisions.

Risk Factors of Infection in Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide and Dexamethasone (Rd) Regimen: Real-Life Results of a Large Single-Center Study.

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017 and 2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n = 110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5-16.2) months, and the median overall survival was 22.3 (95% CI: 15.9-28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response, and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95% CI: 1.6-11.2, p = 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI: 1.0-6.7, p = 0.048), and anemia grade ≥3 (OR 5.0, 95% CI: 1.8-14.0, p = 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia, and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

Prognostic Value of Resistance Proteins in Plasma Cells from Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.

While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1-7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13-0.80, p = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.