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.

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.

Mechanism of Silylation of Vinyl Arenes by Hydrodisiloxanes Driven by Stoichiometric Amounts of Sodium Triethylborohydride-A Combined DFT and Experimental Study.

The reactions of vinyl arenes with hydrodisiloxanes in the presence of sodium triethylborohydride were studied using experimental and computational methods. The expected hydrosilylation products were not detected because triethylborohydrides did not exhibit the catalytic activity observed in previous studies; instead, the product of formal silylation with dimethylsilane was identified, and triethylborohydride was consumed in stoichiometric amounts. In this article, the mechanism of the reaction is described in detail, with due consideration given to the conformational freedom of important intermediates and the two-dimensional curvature of the potential energy hypersurface cross sections. A simple way to reestablish the catalytic character of the transformation was identified and explained with reference to its mechanism. The reaction presented here is an example of the application of a simple transition-metal-free catalyst in the synthesis of silylation products, with flammable gaseous reagents replaced by a more convenient silane surrogate.

Catalytic and non-catalytic hydroboration of carbonyls: quantum-chemical studies.

The addition of hydroboranes across several unsaturated moieties is a universal synthetic tool for the reduction or functionalization of unsaturated moieties. Given the sustainable nature of this process, the development of more environmentally-benign approaches (main-group catalysis or uncatalysed approaches) for hydroboration has gained considerable recent momentum. The present paper examines both catalyst-free and KF-mediated hydroboration of carbonyl compounds with the use of quantum-chemical methods. The results of computations for several potential reaction pathways are juxtaposed with experiment-based calculations, which leads to stepwise mechanisms and energy profiles for the reactions of pinacolborane with benzaldehyde and acetophenone (in the presence of KF). For each step of these reactions, we provide an accurate description of the geometric and electronic structures of corresponding stationary points. Five different levels of theory are employed to select the most applicable theoretical approach and develop a computational protocol for further research. Upon selection of the best-performing methods, larger molecular systems are studied to explore possible more complex pathways at the M06-2X/6-311++G(2d,p) and ωB97XD/6-311++G(2d,p) levels of theory, which brings up multi-pathway, overlapping catalytic cycles. The mechanism of solvent-free, catalyst-free hydroboration of aldehydes is also revisited through the prism of the elaborated methodology, which leads to a whole new perspective on the pathways of this and similar reactions, with a multimolecular cascade of hydride transfers being more energetically favoured than a four-membered transition state.

Stem cell mobilization in multiple myeloma patients relapsing after previous autologous hematopoietic stem cell transplantation: A multicenter report by the Polish Myeloma Study Group.

BACKGROUND: Salvage autologous hematopoietic stem cell transplantation (autoHSCT) may be used to treat relapse of multiple myeloma occurring after previous autoHSCT. When insufficient number of hematopoietic stem cells was stored from the initial harvest, remobilization of stem cells is necessary. PURPOSE: The analysis of stem cell remobilization after previous autoHSCT. PATIENTS AND METHODS: Fifty-eight patients, 60% males, median 59 years, were included. Median time interval between autoHSCT and remobilization was 42 months. The first remobilization was performed mostly after chemotherapy: cyclophosphamide (33%), cytarabine (43%), and etoposide (19%). RESULTS: The first remobilization was successful in 67% patients. About 19% patients required plerixafor rescue, among whom it allowed for successful harvesting in 14%. Use of cyclophosphamide, cytarabine, and etoposide allowed for successful remobilization in 53%, 84%, and 55% patients, respectively. Patients treated with cytarabine had the highest yield of CD34+ cells (median 7.5 × 106 /kg vs 5.8 and 2.4 for etoposide and cyclophosphamide, P = .001). Higher percentage of patients was able to collect ≥2 × 106 CD34+ cells/kg during one leukapheresis after cytarabine (76% vs 21% for cyclophosphamide vs 36% for etoposide, P = .001). Cytarabine use was associated with lower risk of remobilization failure OR = 0.217, P = .02. Toxicity comprised mostly hematological toxicity (thrombocytopenia and neutropenia). One patient succumbed to septic shock. CONCLUSION: Remobilization after previous autoHSCT is feasible only in a proportion of patients. Cytarabine is associated with the highest rate of successful mobilization and the highest yield of mobilized CD34+ cells. The toxicity requires careful surveillance of these patients.

miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 expressions in autologous hematopoietic stem cell transplantation and their impact on engraftment.

OBJECTIVE: MicroRNAs engaged in angiogenesis and hematopoiesis can influence hematopoietic stem cells (HSCs) homing after transplantation by targeting bone marrow niche microenvironment. This study aimed to examine the kinetics of miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 in autologous HSC transplantation settings. METHODS: The study comprised of 51 patients with hematological malignancies (42 multiple myeloma, 9 lymphoma). Samples were taken at four time points: before conditioning, after chemotherapy but prior to autologous HSC transplantation (day 0), on day +7, and +14 days after HSCT. The miRNA levels were evaluated by the real-time PCR method. RESULTS: A significant, steady decline of all tested microRNAs in the course of transplantation, as compared to the baseline, was found. The study revealed that higher levels of miRNA-15a, miRNA-16, miRNA-126, and miRNA-146a on day 0 correlated with longer time to engraftment. Additionally, a positive correlation between the levels of miRNA-15a, miRNA-146a, and miRNA-223 assessed on day +7 and the time to engraftment was observed. CONCLUSIONS: In conclusion, all investigated microRNAs changed significantly in the course of transplantation. Our results suggest that the miRNAs may participate in hematopoietic recovery in the early post-transplant period and influence engraftment efficiency after HSCT.

VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment.

As a site of complicated interactions among cytokines, bone marrow niche has been the subject of many scientific studies, mainly in the context of the proteins influencing damage or recovery of endothelium after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we aimed at exploring mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. The aim of our study was to evaluate levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous HSCT and to examine their influence on hematological recovery. Forty-three patients with hematological malignancies (33 multiple myeloma, 10 lymphoma) were enrolled in the study. Plasma samples were taken at five time points: before conditioning treatment (BC), on transplantation day (0) and 7 (+7), 14 (+14), and 21 (+21) days after HSCT. The cytokine levels were evaluated by ELISA method. Our study revealed decreased levels of VEGF, ANGPT1, and MMP-9 in the early post-transplant period as compared to the baseline (BC). ANGPT2 was decreased after conditioning treatment, but tended to increase from day +7. On day +7, positive correlations between ANGPT1 level as well as MMP-9 and the time to engraftment were observed. As opposite to ANGPT1, negative correlation between ANGPT2 level on day +7 after HSCT and the time to hematological recovery was noticed. Our study suggests that investigated cytokines are an important part of bone marrow environment and significantly influence the time to engraftment after HSCT.

Safety and feasibility of therapeutic platelet depletion with Spectra Optia in a pregnant woman.

INTRODUCTION: Thrombocytapheresis is an alternative treatment beneficial in rare circumstances, when cytoreductive agents are contraindicated, drug therapy gave no response or the expected response would be too slow. Here we present a case of a pregnant woman who underwent 5 thrombocytaphereses using Spectra Optia device to reduce circulating platelets (PLT) count and prepare for Cesarian section. PATIENT CHARACTERISTICS AND PERFORMED TREATMENT: A 39-year-old woman with diagnosed chronic myeloid leukemia (CML) was treated with interferon because of too high PLT count. The treatment was well tolerated but the effect was not satisfactory (PLT count remained high). Because of high risk of bleeding during childbirth, the healthcare providers decided to perform thrombocytapheresis to reduce circulating PLT count below 1000×10E3/µl, and to prepare the patient for a planned Cesarean section. The results are presented as mean±SD. RESULTS: Five therapeutic aphereses procedures were performed, with a Spectra Optia device (TerumoBCT). A mean of 1.3±0.3 total blood volume was processed and we observed a mean PLT drop of 42.3±17.7%. Each apheresis procedure resulted in a PLT level ≤1000×10E3/µl. PLT CE1 was high 50.6±2.6% and reproducible. The white blood cell (WBC) loss was low (18.5%±11.0%). No adverse effects were observed. CONCLUSION: Therapeutic platelet depletion using the Spectra Optia™ Apheresis System can be effective and safe during pregnancy. Thrombocytapheresis procedures were reproducible and Spectra Optia system successfully adjusted settings to each procedure conditions. Thrombocytapheresis seems to be a viable and safe option even in pregnant women.

Increased efficacy of intermediate-dose cytarabine + G-CSF compared to DHAP + G-CSF for stem cell mobilization in patients with lymphoma: an analysis by the polish lymphoma research group.

Salvage regimens, like DHAP (dexamethasone, cytarabine, and cisplatin) are frequently used for stem cell mobilization in lymphoma. The aim of this study was to compare the efficacy of DHAP + G-CSF with intermediate-dose cytarabine (ID-AraC) + G-CSF, recently proposed as an alternative schedule. Consecutive patients with Hodgkin's or non-Hodgkin lymphoma who had received at least 2 lines of chemotherapy, mobilized with either DHAP (n = 51) or ID-AraC (n = 50) + G-CSF were included in the analysis. AraC was administered at the dose of 400 mg/m [1] bid intravenously for 2 days followed by filgrastim starting from day 5. In the AraC group, 96 % of patients collected at least 2 × 10 [2] CD34(+) cells/kg compared to 71 % in the DHAP group (p = 0.0006). The CD34(+) cell yield was 9.3 (0-30.3) × 10 [2]/kg vs. 5.6 (0-24.8) × 10 [2]/kg, respectively (p = 0.006). A single apheresis was sufficient to achieve the threshold number of CD34(+) cells in 82 % of the cases after AraC compared to 45 % after DHAP (p = 0.001). We conclude that stem cell mobilization using ID-AraC is associated with a significantly higher efficacy than DHAP, allowing for collection of the transplant material in almost all patients with lymphoma. Our observation suggests that ID-AraC + G-CSF may be a preferable mobilization regimen in this setting.

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.

Inflammation-related mRNA expression in patients with multiple myeloma undergoing hematopoietic stem cell mobilization.

Mobilization of CD34+ cells is a key element in the therapy of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation. The use of chemotherapy and the granulocyte colony-stimulating factor can significantly affect the expression of inflammation-related proteins and the migration of hematopoietic stem cells. We assessed the mRNA expression of selected proteins involved in the inflammatory landscape in patients with MM (n = 71). The study aimed to evaluate C-C motif chemokine ligands 3, 4, 5 (CCL3, CCL4, CCL5), leukocyte cell-derived chemotaxin 2 (LECT2), tumor necrosis factor (TNF), and formyl peptide receptor 2 (FPR2) levels in the course of mobilization and their role in the CD34+ collection efficacy. mRNA expression from peripheral blood (PB) plasma was evaluated by Reverse transcription polymerase chain reaction. We observed a deep decline in CCL3, CCL4, LECT2, and TNF mRNA expression on the day of the first apheresis (day A) compared with that at baseline. A negative correlation was observed between CCL3, FPR2, LECT2, TNF level, and the CD34+ cells count in PB on day A, and the number of CD34+ cells obtained at first apheresis. Our results indicate that the investigated mRNAs significantly alter and may regulate the migration of CD34+ cells during mobilization. Moreover, in the case of FPR2 and LECT2, the results obtained in patients differed from the murine models.

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.

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.

Hydrogermylation initiated by trialkylborohydrides: a living anionic mechanism.

Sodium trialkylborohydrides were found to be initiators of selective hydrogermylation of aromatic alkenes. Addition of phenylgermane and diphenylgermane in the presence of 10 mol% of NaHB(sec-Bu)3 proceeded in a highly selective manner to give - in contrast to the analogous hydrosilylation process - ß-germylated products. The nature of this process was explained with the aid of DFT calculations and it was proposed that the mechanism proceeds via a trisubstituted germanide anion whose attack on the terminal vinyl carbon is the source of selectivity.

SIRT1-SIRT7 Expression in Patients with Lymphoproliferative Disorders Undergoing Hematopoietic Stem Cell Mobilization.

Sirtuins are involved in the fate of hematopoietic stem cells (HSCs), including their metabolism, stress response, differentiation, migration, and apoptosis. The aim of this study was to explore SIRT1-7 expression during HSC mobilization. The study included 50 patients with lymphoproliferative disorders (39 multiple myeloma, 11 lymphoma). Samples were taken before mobilization (day 0) and on the day of first apheresis (day A). The sirtuin expression was evaluated by the Droplet Digital PCR (ddPCR) method. A significant increase of the SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 levels measured at day A as compared to baseline was observed. The study revealed a positive correlation between SIRT5, SIRT6, and SIRT7 expression and the CD34+ peak value in peripheral blood and the number of CD34+ cells collected on day A. Patients from the SIRT7 "high expressors" group collected more CD34+ cells on day A than "low expressors". Upregulated expressions of SIRT3 and SIRT7 on the day of first apheresis were observed in patients in complete remission status (CR) as compared to the non-CR group. Our results suggest that the investigated sirtuins may influence the HSC migration and hematopoietic landscape during mobilization. SIRT5, SIRT6, and SIRT7 may be associated with the efficacy of HSC mobilization.

Alterations in microRNA Expression during Hematopoietic Stem Cell Mobilization.

microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation. The miRNA level was evaluated by RT-PCR. Compared to baseline, a significant decline in hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, and hsa-miR-155-5p was observed on the day of the first apheresis (day A). An increase was observed only in the expression of hsa-miR-34a-5p. On day A, a negative correlation was found between hsa-miR-15a-5p and hsa-miR-146a-5p levels and the number of CD34+ cells in peripheral blood. A negative correlation was observed between hsa-miR-146a-5p and the number of collected CD34+ cells after the first apheresis. Good mobilizers, defined according to GITMO criteria, demonstrated a lower hsa-miR-146a-5p level on day A than poor mobilizers. Patients from the hsa-miR-146a-5p "low expressors" collected more CD34+ cells than "high expressors". Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization.

Salvage autologous hematopoietic stem cell transplantation for multiple myeloma performed with stem cells procured after previous high dose therapy - a multicenter report by the Polish Myeloma Study Group.

Salvage autologous hematopoietic stem cell transplantation (auto-HSCT) constitutes a therapeutic option for a group of well-selected patients with relapsed multiple myeloma (MM). However, if an insufficient number of stem cells were harvested and stored before the first auto-HSCT, stem cells need to be remobilized. Patients diagnosed with MM who following relapse after auto-HSCT, had remobilization and afterward, auto-HSCT with remobilized cells were included in this retrospective analysis. Thirty-three patients, 61% males, the median age 61 years, were included. With a median follow-up of 1.8 years, 2-year progression-free survival was 56.2%, non-relapse mortality 4.8%. The 2-year cumulative incidence of t-MDS was 4.9%. Factors important for the outcome were: the quality of response, previous radiotherapy, the time between the first and salvage auto-HSCT. To conclude, salvage auto-HSCT performed with cells procured after the previous auto-HSCT can be efficacious in relapsed MM, especially if a sufficiently long response had been obtained to the first auto-HSCT(s).

Associations of ficolins and mannose-binding lectin with acute myeloid leukaemia in adults.

We investigated clinical associations of ficolins and mannose-binding lectin (MBL) in 157 patients suffering from acute myeloid leukaemia (AML). Concentrations of ficolin-1, ficolin-2, ficolin-3 and MBL (before chemotherapy) in serum were determined as were selected polymorphisms of the corresponding genes (FCN1, FCN2, FCN3 and MBL2). The control group (C) consisted of 267 healthy unrelated individuals. Median level of ficolin-1 in patients was lower (p < 0.000001) while median levels of ficolin-2, ficolin-3 and MBL were higher (p < 0.000001, p < 0.000001 and p = 0.0016, respectively) compared with controls. These findings were generally associated with AML itself, however the highest MBL levels predicted higher risk of severe hospital infections (accompanied with bacteremia and/or fungaemia) (p = 0.012) while the lowest ficolin-1 concentrations tended to be associated with prolonged (> 7 days) fever (p = 0.026). Genotyping indicated an association of G/G homozygosity (corresponding to FCN1 gene - 542 G > A polymorphism) with malignancy [p = 0.004, OR = 2.95, 95% CI (1.41-6.16)]. Based on ROC analysis, ficolin-1, -2 and -3 may be considered candidate supplementary biomarkers of AML. Their high potential to differentiate between patients from non-malignant controls but also from persons suffering from other haematological cancers (multiple myeloma and lymphoma) was demonstrated.

Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG).

We present the results of a prospective, non-randomized phase 2 trial in which 253 AML patients (pts) under 60 years old received DAC (Daunorubicin + AraC + Cladribine) as first induction followed by CLAM (Cladribine + AraC + Mitoxantrone) as early second induction on day 16 based on bone marrow (BM) blasts on day 14 (D14). The CR/CRi rate after a single course of DAC was 83% for pts with D14 BM blasts less than 10%. Forty-six pts had >10% BM blasts on D14, of whom 35 received CLAM with rates of CR/CRi 60% and early death (ED) 23%. The remaining 11 pts were not fit to receive CLAM, with rates of CR/CRi 28%, PR 18%, and ED 18%. Median OS was 7.2 versus 7.5 months, respectively. The overall CR/CRi rate was 77% after the first induction, with final CR/CRi rate 80% after DAC reinduction for pts who achieved PR with initial DAC course. CLAM used as early second induction might improve CR/CRi rates for younger AML pts with poor early response to DAC induction, but may be associated with higher mortality.

Associations of Ficolins With Hematological Malignancies in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantations.

A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between "self" "abnormal self," and "non-self" and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation via the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the corresponding (FCN1, FCN2, and FCN3) genes. Serum samples were collected before conditioning chemotherapy, before HSCT, and once weekly post-HSCT (four to five samples in total); some patients were also sampled at 1 and/or 3 months post-transplantation. The control group (C) consisted of 267 healthy unrelated individuals. Median ficolin-1 and ficolin-2 (but not ficolin-3) levels in MM patients' sera taken before chemotherapy were lower (and correspondingly frequencies of the lowest concentrations were higher) compared with controls. That appeared to be associated with the malignant disease itself rather than with post-HSCT complications (febrile neutropenia, infections accompanied, or not with bacteremia). Higher frequencies of the FCN1 genotype G/A-C/C-G/G (corresponding to polymorphisms at positions -542, -144, and +6658, respectively) and FCN2 gene heterozygosity for the -857 C>A polymorphism were found among patients diagnosed with MM compared with the C group. Furthermore, FCN2 G/G homozygosity (-557 A>G) was found more frequently and heterozygosity G/T at +6424 less frequently among LYMPH patients than among the healthy subjects. Heterozygosity for +1637delC mutation of the FCN3 gene was more common among patients diagnosed with lymphomas who experienced hospital infections. Although no evidence for an association of low ficolin-1 or ficolin-2 with infections during neutropenia following chemotherapy before HSCT was found, we observed a possible protective effect of ficolins during follow-up.