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Microglia are the resident immune cells of the central nervous system, playing a role in the inflammatory process development and resolution, presenting two main phenotypes, pro-inflammatory M1, and anti-inflammatory M2. Therapies affecting the microglia phenotype may be beneficial in treating inflammatory neurodegenerative diseases. In our experiments, we used the animal multiple sclerosis model, experimental allergic encephalomyelitis (EAE). Rats were treated during the pre- or symptomatic phase of the disease with cyclophosphamide, followed by hematopoietic stem cell transplantation, and with/without post-transplantation cyclophosphamide. Our study aimed to analyze the microglia phenotype in animals subjected to this treatment. The number of M1 cells in the spinal cord, and inducible nitric oxide synthase (iNOS) levels in the brain were similar in all experimental groups. The differences were observed in M2 cells number and arginase 1 (Arg1) levels, which were decreased in EAE animals, and increased after treatment in the symptomatic phase of EAE, and in the pre-symptomatic phase, but only with post-transplantation cyclophosphamide. Analysis of gene expression in the brain showed decreased iNOS expression in EAE animals treated in the symptomatic phase of EAE and no differences in Arg1 expression. Results indicate that treatment applied to experimental animals influences the microglia phenotype, promoting differentiation towards M2 cells.

The outbreak of the COVID-19 pandemic presented the world with many new challenges such as rapid and accurate diagnosis of infected individuals. RT-PCR has become the gold standard in COVID-19 diagnostics, but its limitations are: long turnaround time and the need to be conducted by specialized staff. The need for rapid and easy-to-use diagnostic tests led to the development of ID NOW — a rapid molecular test that provides a COVID-19 diagnosis in less than 15 minutes and can be performed by support staff in point-of-care (POC) locations. It can also detect other infections with similar symptoms, such as influenza or RSV. Due to rapid differentiation between COVID-19 and other infections patients can be isolated quickly and hospital departments operate efficiently. In this publication we present the recommendations for the use of the diagnostic test ID NOW based on clinical research results and opinions of experts in different medical fields.

Hematopoietic stem cell transplantation (HSCT) is now evolving into a standard treatment in some autoimmune diseases (AD) alongside other modern therapy. The main indications are multiple sclerosis and systemic sclerosis for which HSCT has become an integral and standard-of-care part of treatment algorithms. From 1994 to the beginning of 2021, data from the EBMT Registry indicates that 3,442 patients (60% females, 40% males; 91% adults, 9% pediatric) received 3,514 transplant procedures for autoimmune diseases, with over 90% receiving autologous transplant. Autoimmune diseases are currently the fastest growing indication for autologous HSCT in European Society for Blood and Marrow Transplantation (EBMT), whilst allogeneic HSCT for ADs is mainly restricted to pediatrics, especially diseases with a genetic component. Patient selection plays a key role in providing the best risk/benefit ratio of the procedure. Intensity of conditioning regimen and center experience are also important. Ultimately, the future of HSCT for ADs depends on the standard of care therapy, which influences uptake within national/international disease specialist communities. Further studies are necessary in order to establish relative benefit over current/future standard of care therapy, to establish the best HSCT regimen for each disease, to define mechanisms, develop clinical biomarkers to help select and monitor patients, and to define health economic benefits and public health delivery. We present a current perspective summarizing activity across EBMT, including centers in Poland.

Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC)2 mg/dL or estimated glomerular filtration rate (eGFR) 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria.We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR 60 mL/min, treated with ASCT from 1998 to 2004.The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC1.4 mg/dL and eGFR 55mL/min.We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients’ quality of life. One of the preventive strategies for OM is cryotherapy. We retrospectively analyzed whether commercially available ice-cream could prevent OM during the melphalan infusion. We retrospectively analyzed 74 patients after AHSCT to see whether there is any correlation between OM and cryotherapy (ice-cream), melphalan dose (140 mg/m2 or 200 mg/m2). The incidence of OM in our study inversely correlated with cryotherapy in the form of ice-cream. Out of 74 patients receiving conditioning chemotherapy with high-dose melphalan, 52 received cryotherapy. Fifteen patients in the cryotherapy group (28.84%) developed OM, whereas 13 patients (59.09%) developed it in the group without cryotherapy. In a multiple linear regression test cryotherapy remained a significant protective factor against OM (p = 0.02) We have also seen the relationship between melphalan dose with OM (p

Hypoxic-ischaemic encephalopathy (HIE) is a severe complication of asphyxia at birth. Therapeutic hypothermia, the standard method for HIE prevention, is effective in only 50% of the cases. As the understanding of the immunological basis of these changes increases, experiments have begun with the use of cord blood (CB) because of its neuroprotective properties. Mechanisms for the neuroprotective effects of CB stem cells include antiapoptotic and anti-inflammatory actions, stimulation of angiogenesis, production of trophic factors, and mitochondrial donation. In several animal models of HIE, CB decreased oxidative stress, cell death markers, CD4+ T cell infiltration, and microglial activation; restored normal brain metabolic activity; promoted neurogenesis; improved myelination; and increased the proportion of mature oligodendrocytes, neuron numbers in the motor cortex and somatosensory cortex, and brain weight. These observations translate into motor strength, limb function, gait, and cognitive function and behaviour. In humans, the efficacy and safety of CB administration were reported in a few early clinical studies which confirmed the feasibility and safety of this intervention for up to 10 years. The results of these studies showed an improvement in the developmental outcomes over hypothermia. Two phase-2 clinical studies are ongoing under the United States regulations, namely one controlled study and one blinded study.

Experimental allergic encephalomyelitis (EAE) is the animal model of multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (AHSCT) has recently been recognized as the standard treatment for MS. The aim of our experiment was to investigate the effect of AHSCT with the addition of low-dose post-transplantation cyclophosphamide (Cy) on EAE in rats. Low dose post-transplantation Cy is used in haploidentical HSCT to reduce the risk of graft versus host disease. We hypothesized that it could bring additional benefit in autologous HSCT in autoimmune diseases. Rats with evoked EAE were treated with high dose (125 mg/kg) Cy, followed by AHSCT or high dose (125 mg/kg) Cy followed by AHSCT followed by low dose (20 mg/kg) Cy in two-time schedules—with the therapy applied during the pre-symptomatic or symptomatic phase of the disease. Both AHSCT and AHSCT with post-transplantation Cy in accordance with both time schedules reduce the intensity of the inflammatory response in the CNS, in comparison with non-treated EAE rats. The reduction of clinical symptoms was present in all AHSCT treatment protocols, however, it was significantly stronger when post-transplantation Cy was given during the symptomatic phase of the disease. AHSCT with the addition of post HSCT low dose Cy improved the results of AHSCT by not only reducing the intensity of inflammation in the CNS but also by significantly reducing the clinical symptoms in treated animals when compared to AHSCT alone. We provide an experimental rationale that the addition of post-transplantation Cy may improve the outcome of HSCT in MS. Graphic Abstract

Item does not contain fulltext The current guidelines for prevention of infections in hematopoietic stem cell transplantation (HSCT) do not specify which central venous catheter (CVC) insertion site should be preferred in allogeneic HSCT recipients-internal jugular vein (IJV) or subclavian vein (SCV). We designed a multicenter prospective observational study comparing the risk of infectious and non-infectious complications between the two most common sites of CVC insertion (IJV and SCV) in allogeneic HSCT. There were in total 232 consecutive patients (86 IJV and 146 SCV) who underwent adult allogeneic HSCT reported from 11 centers in 8 countries. The center independent analysis of central line associated/related blood stream infections with ECDC criteria has shown statistically significant difference favoring SCV (23% IJV vs 13% SCV (OR 2.03 (1.01-4.06), p = 0.047)). The differences in CLABSI per 1000 days of CVC use favored SCV over IJV (7.93/1000 days IJV vs 2.79/1000 days SCV, p = 0.002). The frequency of all non-infectious complications was similar in both arms-13% IJV and 12% SCV (OR 1.1 (0.5-2.5), p = 0.8). This multicenter prospective study showed statistically significant lower confirmed number of CLABSI per 1000 days of CVC use without higher risk of noninfectious complications related to the subclavian insertion site in allogeneic HSCT recipients.

Objectives To provide real-world data on the impact of autologous hematopoietic stem cell transplantation (AHSCT) on treatment costs of patients with multiple sclerosis (MS) in Poland. Methods Medical data of 105 patients who underwent AHSCT in the years 2011 to 2016 were obtained from the National Health Fund (NHF) database. Treatment costs were calculated from the public payer’s perspective per patient-year for the total available period as well as 12 months before and after AHSCT. The statistical analysis was performed using MATLAB 2016b. Results Mean treatment-related costs covered by the NHF per patient-year before and after the transplantation were €4314.9 and €1188.8 , respectively. The average cost of disease-modifying drugs per patient was reduced from €2497.9/year before to €65.3/year after AHSCT. Conclusions Although the initial cost of AHSCT is high, the costs involving AHSCT and post-AHSCT treatment could, according to our analysis, pay off in 3.9 years, when compared to the costs of disease-modifying drug therapy in aggressive MS. The study provides evidence that the AHSCT can lead to significant savings in treatment costs of aggressive MS from the public payer’s perspective.

Background Bone marrow harvest (BMH) for haematopoietic stem cell transplantation is a well-established procedure. The guidelines of World Marrow Donor Association provide information on donor selection. However, some of the guidelines regarding donors with anaemia prior to harvest lack in supporting data from clinical studies. With this study, we aimed to provide such data. Material and methods In this retrospective, single-centre study, we analysed the interplay between haemoglobin levels and BMH and BMH impact on haemoglobin levels in a cohort of 149 unrelated BM donors, including 13 subjects with mild anaemia. Results The BMH led to significantly lower decrease in haemoglobin levels in donors with anaemia than in control group (1·79 g/dl vs. 2·56 g/dl, P 0·05). Median BM volume harvested from anaemic donors was 16·34 ml/kg; none of them required blood transfusion after BMH. Conclusion Mild anaemia prior to BMH does not significantly impact the collection results. The BMH is safe and feasible in donors with mild anaemia.

Background Recently, novel protocol utilizing Continuous Mononuclear Cell Collection (cMNC) have been introduced for leukapheresis. We compared the efficacy of cMNC with an older protocol – mononuclear cell collection (MNC) for CD34+ cell collection in unrelated donors with negative stem cell collection predictors. Material and methods Retrospective data from a series of 258 consecutive unrelated hematopoietic stem cell donors was included in this single-center study (80 donors collected with cMNC and 178 with MNC). The donors with poor predictors for collection such as low number of circulating CD34+ cells and/or weight disproportion were assigned to the cMNC arm. Results The cMNC protocol yielded a higher number of CD34 + cells per donor body weight (7.63 × 106/kg vs 6.82 × 106/kg, p = 0.027). One apheresis was sufficient for collection of target cell number in 89% individuals from both groups despite negative predictors in the cMNC group. In donors with CD34 + cell count Conclusion cMNC protocol is more efficient in donors with low pre-apheresis CD34+ cell count and weight disproportion between donor and recipient. This suggests that the use of cMNC in unrelated donors could possibly further improve the results of HSC collections.

Very few reports have been published to date on the bloodstream infections caused by Saccharomyces spp. in oncohaematological patients, and there are no guidelines on the use of this probiotic microorganism in this population. We describe the use of probiotic preparation containing Saccharomyces boulardii in a large group of oncohaematological patients. We retrospectively analysed the data from 32,000 patient hospitalisations at the haematological centre during 2011–2013 (including 196 haematopoietic stem cell transplant recipients) in a tertiary care university-affiliated hospital. During the study period, 2270 doses of Saccharomyces boulardii probiotic were administered to the oncohaematological patients. In total, 2816 mycological cultures were performed, out of which 772 (27.4%) were positive, with 52 indicating digestive tract colonisation by Saccharomyces spp., mainly in patients with acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM). While colonised, they were hospitalised for 1683 days and 416 microbiological cultures of their clinical samples were performed. In the studied group of patients, there were six blood cultures positive for fungi; however, they comprised Candida species: two C. glabrata, one C. albicans, one C. krusei, one C. tropicalis and one C. parapsilosis. There was no blood culture positive for Saccharomyces spp. Our study indicates that despite colonisation of many oncohaematological patients with Saccharomyces spp., there were no cases of fungal sepsis caused by this species.

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p

Background Single positive staphylococcal blood culture in a hematopoietic stem cell transplantation (HSCT) recipient is generally regarded as contamination. Such a blood culture (BC) does not fill the criteria for Laboratory-Confirmed Bloodstream Infection (LCBI) and could be described as Single Positive Commensal Blood Culture. The aim of this retrospective cohort analysis was to determine the clinical significance of SPCBC in HSCT recipients. Methods 206 patients transplanted between 2007 and 2013 were followed until January 2015. Results The 100-day survival for patients without positive BC was 99.6% compared with 83.9% for LCBI and 82.8% for SPCBC (p = 0.0036). The 5-year overall survival (5yOS) was 67.1% for patients without positive BC, 44.9% for LCBI, 34.0% for SPCBC (p Conclusion To our knowledge this is the first report that specifically shows that short- and long-term survival after HSCT is significantly lower in patients who experience an episode of SPCBC with Staphylococcus spp. during HSCT hospitalization.

Objectives We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies. Methods The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found. Results Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from –0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D–based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia. Conclusions There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.

Background: Bone marrow biopsy and aspiration (BMBA) is a diagnostic procedure within the field of internal medicine. The intensity of the pain felt by the patients often goes unrecognized by the medical staff. No extant studies have addressed pain intensity experienced during each particular step of a BMBA. Objectives: The aim was to analyze the pain intensity and explore the extent to which the technique applied by the doctor performing the biopsy influences the pain level. Methods: A survey comprising 17 questions was created and it addressed characteristics of the patients, previous experience and pain intensity on each step of the procedure. Results: 125 patients were enrolled into the study. Age (p = 0.009), gender (p = 0.02), pain during previous biopsies (p

Background In the recent years the population of registered unrelated hematopoietic stem cell donors in Poland expanded to over 768 000 in 2014. In parallel the number of hematopoietic stem cell donations rose to over 900 in 2014. So far there are very little data about unrelated hematopoietic stem cell donors in Poland. Aims Analysis of most common deferral reasons of unrelated hematopoietic stem cell donors at the time of final clearance before transplantation. Methods 465 medical records of unrelated donors who underwent final clearance were analyzed. The deferral reasons were analyzed and compared with recent World Marrow Donor Association (WMDA) and National Marrow Donor Program (NMDP) guidelines for donor selection. Results 1.5% of donors were permanently deferred at the final clearance – mostly with random medical conditions. 8% of donors (n = 38) were temporarily deferred at the final clearance. Among them the deferral causes included: suspicion of recent or ongoing Toxoplasmosis (n = 17); autoimmune thyroiditis (n = 3); ongoing CMV infection (n = 2) and other reasons (n = 16). The median time of temporal deferral was 6 weeks. Except for the cases with suspicion of Toxoplasmosis, the temporal deferral over 3 weeks results in very low chances of donation (5%, n = 19). Conclusion The percentages of permanent deferrals are low in Polish donors. The temporal deferrals are mostly based on suspicion of infectious diseases. The temporal deferrals of over 3 weeks in most of the cases effectively block the donation possibility.

The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

BACKGROUND AND OBJECTIVES Many consider volunteer blood donors as ideal candidates for unrelated haematopoietic progenitor cell (HPC) donation. However, frequent blood donations could influence the results of HPC mobilization. To our best knowledge, there are no data on the possible impact of repeated blood donation on efficiency of subsequent HPC mobilization by granulocyte colony-stimulating factor (G-CSF). MATERIALS AND METHODS We compared outcomes of HPC mobilization in unrelated donors with and without a history of blood donation. We conducted a prospective study on 287 consecutive donors admitted to the Department of Hematology since January 2016. The final analysis included 153 donors who agreed to take part in the study and had undergone stem cell mobilization with G-CSF. RESULTS History of blood donations prior to haematopoietic stem cell mobilization with G-CSF does not have a significant impact on the number of collected CD34+ cells in the first leucocytapheresis (516.2 x 106 (170-1148) in blood donors vs 490.5 x 106 (101-1154) in non-donors) (P = 0.32). In all donors, in this study mobilization of HPC was successful: 87.5% of blood donors and 85.6% of non-donors collected the required cell number in a single apheresis. In blood donors, a higher number of blood donations within 2 and 5 years prior to HPC mobilization correlated significantly with successful donation within one leucocytapheresis (P = 0.014 and P = 0.024, respectively). CONCLUSION Multiple blood donations do not significantly influence the outcome of HPC collection in unrelated donors. Blood donors and non-donors have similar results of HPC collection, so there is no reason to favour either group.

Aims To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes. Methods APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months. Results Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis. Conclusions The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure.

Introduction Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. Aims To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. Patients and methods Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. Results In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. Conclusions Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.

Autologous hematopoietic stem cell transplantation (AHSCT) is an emerging treatment option in new onset type 1 diabetes (T1DM), leading to a remission of the T1DM for a longer time period in up to 50 % of patients. The aim of the study was to analyze the cost-effectiveness of this treatment option compared with standard insulin therapy.The medical records of patients who had undergone immunoablation with AHSCT for new onset T1DM were analyzed for the cost-effectiveness of the treatment using the IMS CORE Diabetes Model.The expected survival of patients with T1DM treated solely with insulin (without transplantation) was estimated to be 34.4 years, and their quality-adjusted survival was 13.8 QALY, whereas the expected survival of the patients treated with AHSCT was 34.9 years when the HbA1c benefit over standard treated patients lasted for 2, 35.4 years with 8-year benefit and even up to 40.3 years with the lifelong benefit scenario. Values under the threshold of ICER were reached after 8 years of sustained benefit in terms of HbA1c concentration. If discounting was not applied, the threshold values were reached after 3 years of HbA1c benefit over the standard group, independent of insulin use after transplantation.The results of our study show that hematopoietic stem cell transplantation could be cost-effective in treating new onset T1DM, providing that the benefits of the transplantation lasted over 3-8 years, depending on application of discounting.

Objectives Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current “up to date” standard of the bone marrow harvest in unrelated stem cell donors. Methods We analyzed medical data of 187 unrelated hematopoietic stem cell donors who underwent bone marrow harvest without previous peripheral blood stem collection at the center between 2011 and 2015. The methodology of marrow collection includes multiple cells aimed at safety of the procedure e.g. educational movie, modified skin disinfection protocol, cell enumeration during the procedure, reduction of the contamination surfaces and ongoing monitoring of the quality of work of the doctors. Results The total nucleated cell (TNC) count over 2 x 108 per kg of recipient has been reached in 93.6% of harvests. All of the donors harvested more than 1 x 108 per kg of the recipient. There were no donors who required transfusions or had serious adverse events during and after the harvest. Conclusion We describe here the current up-to-date standard of bone marrow harvest which leads to excellent results in majority of donors without causing significant complications during the donation This article is protected by copyright. All rights reserved.

Introduction New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients’ acceptance for risks connected with the MS treatment. Methods The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the “cure” for MS and crucial goals in the treatment. Results One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years (SD = 10.29). The MS forms were as follows: relapsing-remitting (65%), secondary progressive (14%), primary progressive (10%), and other (11%), with mean EDSS score of 3 points (SD = 2.6). For 50% of the patients, relief of symptoms such as fatigue (72%), paresis (66%), and balance disorders (65%) was synonymous with “cure.” The patients with faster progression of the disease were likely to accept risky “curative” treatments—with average 68% accepted mortality risk (p = .003). Over 81% of patients accepted mortality rates over 1% for the treatment that achieves self-defined cure. Conclusion The study shows that the MS patients are likely to accept even very risky treatments as long as they promise patient-defined “cure.”

Background Autologous peripheral blood stem cell transplantation (PBSCT) is commonly used in the treatment of lymphoma patients. G-CSF is widely used to boost white blood cell recovery. However, there are no clear data indicating which strategy of using G-CSF provides the most benefit. The aim of our study was to compare 3 strategies of G-CSF administration: from day +1, from day +5, and no administration. Material and methods Data from 211 patients treated at 3 centers were gathered retrospectively. The patients in the 3 analyzed groups were not different in regard to type of disease, age, sex, and number of CD34+ cells received. Results The 3 strategies of G-CSF dosage had very similar results. G-CSF boosted the recovery of white blood cells and shortened the time of neutropenia. However, there were no differences in confirmed infections and the duration of hospitalization after transplantation. Conclusions Our results question the use of G-CSF in a post-PBSCT setting, as it does not provide significant benefits in reducing the number of infections or shortening the duration of hospitalization.

Examination of the bone marrow biopsy and aspirate allows diagnosis and assessment of various conditions such as primary hematologic and metastatic neoplasms, as well as nonmalignant disorders. Despite being performed for many years, according to many different protocols, the procedure still remains painful for the majority of patients. This paper summarizes the current knowledge of pain reduction measures in the bone marrow biopsy and aspiration.

Introduction High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. Materials and Methods Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Multiple Myeloma Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. Results and Conclusions The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) – was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2) and cyclophosphamide (> 2 g/m2) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.

Autologous hematopoietic stem cell transplant has become a successful treatment option in aggressive autoimmune diseases. Young women who are consulted before this treatment are faced with an absence of data on the transplant's effect on their fertility. The aim of our study was to analyze information on menstruation recovery after autologous hematopoietic stem cell transplant for autoimmune diseases.An anonymous online questionnaire was distributed among members of an international Web forum of patients who had autologous hematopoietic stem cell transplant for autoimmune disease. Data were collated and analyzed.We obtained responses from 28 female patients to the questionnaire. The conditioning regimens used in this population were cyclophosphamide ± antibodies or BCNU (carmustine), etoposide, Ara-C (cytarabine), and melphalan chemotherapy. All patients who were transplanted at the age of 32 years or younger showed restored menstruation after an average (standard deviation) of 5.38 months (5.34 mo). In patients aged 33 to 41 years, menstruation was restored in 38%. We found that 73% of patients already had children before autologous hematopoietic stem cell transplant, and only 15% of responders declared desire for pregnancy after transplant.Our online analysis showed feasibility as a questionnaire for assessing fertility after autologous hematopoietic stem cell transplant. The results show that menstruation is restored in all patients of 32 years of age or younger, regardless of the conditioning regimen. Many of these women are likely to maintain fertility and may eventually become pregnant. However, a significant number of responders who underwent autologous hematopoietic stem cell transplant for autoimmune diseases already had children before transplant and indicated no desire for pregnancy after transplant; the data on pregnancy occurrence in this group should be interpreted in this context.

Background The immunoablation with autologous hematopoietic stem cell transplantation is a new experimental treatment of early diabetes type 1. The treatment is based on destruction of immune system with cytotoxic drugs which leads to halt of immune reaction directed against beta cells of pancreas. During that treatment young patients with diabetes type 1 who are otherwise healthy undergo mobilization with cyclophosphamide (CY) and G-CSF. They are naive to cytotoxic drugs and mobilization is their first contact with chemotherapy. We analyzed the efficiency of mobilization with cyclophosphamide and G-CSF in this population. Methods We analyzed the medical records of 25 patients with diabetes who underwent mobilization with cyclophosphamide and G-CSF. Results The median white blood cell count on the first day of apheresis was 14.6 × 103/μL (range 1.5–33.3) in CY + G-CSF mobilized patients. Median absolute CD 34+ cell count in peripheral blood on the first apheresis day was 0.095 127 × 103/μL (range 0.026–0.477). The median total number of collected CD34+ cells during one or two (if needed) aphereses was 466 × 106 (range 204–816) or 7.24 × 106 CD34+ cells per kg of patient body weight (range 3.03–13.1). There were no poor mobilizers who were unable to collect sufficient cell numbers. Conclusion The mobilization of hematopoietic stem cells with CY + G-CSF in patients with early diabetes type 1 is efficient and the underlying diabetes does not impair the efficiency of hematopoietic stem cell collection.

BACKGROUND This is a single-center, retrospective study in the field of mobilization of hematopoietic stem cell from unrelated donors. We aimed to investigate whether delaying the last G-CSF dose after the start of apheresis influences its results. MATERIAL AND METHODS The medical records of 55 unrelated hematopoietic stem cell donors during the period 2010-2013 were analysed. In this series, 40 received donors the last G-CSF injection prior to the leukapheresis procedure, and 15 received the last injection after apheresis was initiated. RESULTS In the delayed G-CSF application group, more donors had already reached the requested cell number during first apheresis than in the group treated following the standard procedure (73% vs. 35%, respectively; p

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [

Background Central line-associated bloodstream infection (CLABSI) is one of the most common infectious complications after hematopoietic stem cell transplantation. To prevent this complication, international guidelines recommend the implementation of the CLABSI ‘prevention bundle’ consisting of hand hygiene, full barrier precautions, cleaning the insertion site with chlorhexidine, avoiding femoral sites for insertion, and removing unnecessary catheters. The aim of this survey was to analyze to what extent European Group for Blood and Marrow Transplantation (EBMT) centers have included the CLABSI prevention bundle in practice. Methods A questionnaire used for data collection was sent to the 545 EBMT centers worldwide, 103 of which responded. Results All 5 components of the CLABSI prevention bundle were recorded in 28% of the centers' standard operating procedures (SOP), and 21% of the centers answered that they used all of the bundle components in clinical practice. The most common recommendation absent from the SOP was specification of all the components of full barrier precautions (43% of the centers did not include at least 1 component). Skin disinfection with chlorhexidine before catheter insertion was reported by 66% centers. CLABSI rates were monitored in 21% of centers. Conclusions Although most of the centers lacked 1 or more of the CLABSI prevention bundle components in their SOP, improvements could easily be made by updating the centers' SOP. The first important step is introduction of CLABSI rate monitoring in this high-risk patient population.

Plasmapheresis also known as a therapeutic plasma exchange (TPE) is a procedure of plasma removal with it's ineligible plasma's component. Usually it is a supportive measure used simultaneously with the treatment, but in a few diseases, e.g. in trombotictrombocytopenic purpura (TTP), it is a first-choice treatment. During the plasmapheresis plasma is mostly replaced by 20% solution of albumin or combination of 20% solution of albumin and 0.9% solution of NaCl, however in some diseases fresh frozen plasma (FFP) is used. Plasmaphereses have found a wide application in different branches of medicine: hematology, neurology, nephrology, reumatology. Plasmapheresis is an invasive procedure, but when performed by qualified staff it is rather safe and serious complications are very rare.The most common complications of plasmapheresis are mild, usually caused by electrolyte disturbances (hypokalemia, hypokalcemia) or anticoagulation. More serious complication can be associated with FFP transfusion, extracorporeal circulation or presence of intravenous catheter. The latter one is usually necessary to perform the plasmapheresis. In haematology the most common indication for plasmapheresis is the supportive treatment of multiple myeloma. The procedure is performed in patients with high protein levels endangered with hyperviscosity syndrome. Less frequent indications to plasmapheresis in haematology are: Waldenström's macroblobulynaemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), polyneuropaties connected with haematological disorders. Supportive treatment of haemofagocytic syndrome (HLH--hemophagocytic lymphohistiocytosis) is one of the new indications. Plasmaphereses are used in treatment of about 150 different diseases and more and more new needs for this method are identified.

Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children and young adults worldwide. To date, the different immunotherapies tested have achieved insulin independence in

Infections are one of the most common complications after hematopoietic stem cell transplantation (HSCT). Diagnosis is established by analysis of clinical symptoms and results of diagnostic tests such as biochemical panels, microbiological cultures, and visual diagnostics. As the microbiological cultures yield positive results in only some patients and visual diagnostics might miss the infectious source, the diagnosis and proper treatment often depends on clinical assessment supported by laboratory test results. The most commonly used makers of inflammation include C-reactive protein and procalcitonin. However, these tests have serious limitations when used in patients after HSCT. The drugs used in conditioning, neutropenia, and graft-versus-host disease might influence the results of the tests and misguide the physician. In this review, we summarize the current knowledge on profiles of expression of basic markers of inflammation used in clinical practice in patients after HSCT.

Type 1 diabetes mellitus (T1DM) is a metabolic disease caused by autoimmune destruction of beta cells in the pancreas leading to insufficient production of insulin. The standard treatment of diabetes relies on multiple injections of insulin. One of the main drawbacks of this treatment is the inability to replicate timing and action on endogenous insulin secretion when beta cells are intact. Resulting hyper- and hypoglycemias cause long term and acute side effects of the disease. There are multiple approaches to overcome this problem: insulin pumps, oral insulin preparations, immunomodulatory treatments and transplantation of beta cells. This review summarizes recent advances in the treatment of diabetes.

Immunoablation with autologous hematopoietic cell transplantation has shown some effectiveness in the treatment of autoimmune diseases as diverse as aplastic anemia, systemic lupus erythematosus, multiple sclerosis and Crohn's disease. It has been recently shown that this treatment might prevent or delay development of diabetes type 1. The majority of more than 30 patients with early diabetes type 1 who underwent immunoablation and hematopoietic cell transplantation in various centers in the world achieved durable remission of diabetes and independence of exogenous insulin. This review summarizes advantages and risks of this treatment of early diabetes type 1.

The T315I mutation of BCR/ABL gene is known to produce complete resistance of chronic myelogenous leukemia (CML) to all currently available BCR/ABL inhibitors. The data suggesting poor median survival of these patients may indicate that they should be primary candidates for allogeneic stem cell transplantation (alloSCT). However, evidence on efficiency of this treatment modality in CML with T315I mutation is lacking.A 25-year-old patient was diagnosed with Philadelphia chromosome positive CML in accelerated phase. As he did not have an HLA-identical sibling or fully-matched unrelated bone marrow donor, treatment with low dose tyrosine kinase inhibitor - imatinib was initiated. Despite satisfactory hematological remission, he failed to achieve complete cytogenetic remission within the first year of treatment. Moreover, despite escalation of imatinib dosage, the disease relapsed after further 3 months of treatment. Molecular studies revealed T315I mutation of BCR/ABL gene. He responded poorly to interferon alpha (IFN-alpha) and we decided to perform alloSCT from a partially mismatched (8/10 HLA allele match) unrelated donor. The course of transplantation was complicated by staphylococcal sepsis, grade I skin acute GvHD and limited chronic skin GVHD. However, the goal of alloSCT was achieved and the patient remains in complete molecular remission at week +68 post-transplantation.The clinical course of this case supports the idea that allogeneic hematopoietic transplantation is a viable treatment option for patients with CML bearing T315I mutation.