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Introduction: Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue., Methods: This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia., Results: Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients., Conclusion: Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Danger-associated molecular patterns (DAMPs) are molecules that can initiate and maintain robust inflammatory responses and were investigated in the pathogenesis of graft versus host disease (GvHD). Uric acid (UA) and fibrinogen (Fib) are DAMPs released from damaged tissue during allogeneic hematopoietic stem cell transplantation (allo-HCT) and GvHD. We aimed to evaluate the effects of UA and Fib levels on survival in GvHD. One hundred seventy-four patients with grade 2-4 acute GvHD were included. UA and Fib levels were evaluated on allo-HCT day 0 and GvHD on days 0, 7, 14, and 28. Fib GvHD day 0 was the independent predictor for overall survival (OS), non-relapse mortality (NRM), and progression-free survival in multivariable models (HR 0.98, p < 0.001; HR 0.98, p = 0.001, HR 0.98, p = 0.006, respectively). Also UA GvHD day 28 was the independent predictor for OS and NRM (HR 0.77, p = 0.004; HR 0.76, p = 0.011, respectively). Our results indicated that hypouricemia and hypofibrinogenemia were associated with a significantly shorter OS and higher NRM. UA and Fib are remarkable molecules in GvHD because they are routinely utilized, readily available, can be therapeutic targets, and have DAMPs and antioxidant features., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure., Methods: In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not., Results: Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 10 6 /kg in the DM group, while it was 8.2 (1.7-37.3) × 10 6 /kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02)., Conclusion: DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 10 6 /kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 10 6 /kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Objective: We aimed to determine the coronavirus disease 2019 (COVID-19) fear state in haematopoietic stem cell transplant patients and to examine its relationship with quality of life., Methods: In this prospective study, 64 patients who underwent HSCT during the pandemic were included. The COVID-19 fear situation was evaluated with the Fear of COVID-19 Scale (FCV-19S). Quality of life was evaluated with the European Organisation for Quality of Life Research and Treatment Core Questionnaire (EORTC QLQ-C30) (Version 3)., Results: The median FCV-19S score was 16.5 (12.0-22.0). The FCV-19S score was significantly higher in urban residents than rural residents. The general health score was 59.64 ± 20.04. The strongest positive correlation between fear level and life quality was found in emotional function. A weak, significant, positive correlation was observed between role function, nausea-vomiting, pain, appetite loss and fear level., Conclusion: FCV-19S is a quick, safe and valid tool that can be used to determine the COVID-19 fear level in vulnerable patient groups such as HSCT patients and to direct them to the necessary psycho-oncological support., (© 2022 John Wiley & Sons Ltd.)

Introduction: Iron overload (IO) has been shown to be an important cause of mortality and morbidity in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treatment (deferasirox) on survival in alloHSCT recipients in the posttransplant period., Materials and Methods: A total of 80 alloHSCT recipients with IO were analyzed, retrospectively. Pretransplant and posttransplant data were obtained from the patients' files. Patients were divided into two groups. Group 1; patients who did not receive any chelator treatment due to side effects or compliance problems. These patients were treated by phlebotomy. Group 2 consisted of patients who received deferasirox treatment., Results: The median treatment duration with deferasirox was 122 days (min-max:91-225). The iron chelating treatment significantly reduced serum ferritin levels administered at a dosage of 20-30 mg/kg/day (p<0.001). The median OS in Group 1 was found 16.0 (min-max:1.0-63.0) months and 25.0 (min-max:3.0-72.0) months in Group 2. In univariate and multivariate analysis, patients in Group 1 showed poorer OS compared to those in Group 2 with an increase in risk of death (HR:3.22, min-max:1.67-6.23, p=0.001 and HR:3.51,, min-max:1.75-6.99, p<0.001; respectively). The median DFS in Group 1 was found 11.0 (min-max:3.0-24.0) months and 22.0 (min-max:8.0-43.0) months in Group 2. The difference was found statistically significant (p=0.023). The other factors that we found significant difference in multivariate analysis between groups were; presence of acute GVHD (patients with aGVHD had increased risk of death compared to patients without aGVHD (HR:2.49, min-max: 1.32-4.69, p=0.005), chronic GVHD (HR:2.57, min-max:1.23-5.41, p=0.013), median interval to tx (HR: 2.23, min-max:1.17-4.26, p=0.015) and HLA match (HR:3.01, min-max:1.35-6.73, p=0.007) CONCLUSION: Oral deferasirox (Exjade) treatment may improve survival in patients with iron overload who underwent alloHSCT., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives and Aim: Patients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT)., Materials and Methods: We retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients' files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34(+) cell count at the end of mobilization procedure., Results: A total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3×10(6) CD34(+)/kg was 2 in Neupogen® (min-max: 1-4) and Granocyte® (min-max: 1-3) groups and 1 (min-max: 1-2) in Leucostim® group. The median doses of G-CSF agents (μg/kg/day) in PBSC collection procedure were; 10.00 (min-max: 7.00-12.00) in the Neupogen® group, 8.00 (min-max: 7.25-9.00) in the Leucostim® group and 8.50 (6.00-9.50) in the Granocyte® group. There was no statistical significance among groups (p=0.067). The number of total collected PB CD34(+) cells (×10(6)/kg) was 7.64 (min-max: 4.09-13.86) in the Neupogen® group, 13.43 (min-max: 8.15-23.38) in the Leucostim® group and 5.45 (min-max: 4.28-9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34(+) cells compared to patients in the Granocyte® group (p=0.013)., Conclusion: Leucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT., (Copyright © 2013. Published by Elsevier Ltd.)

Invasive fungal pneumonia (IFP) has become increasingly common in patients that previously underwent alloHSCT. The aim of this study was to determine the role of hyperferritinemia, via iron overload in invasive fungal pneumonia in patients that underwent alloHSCT. Medical records of 73 patients with pneumonia that underwent alloHSCT were studied retrospectively, whereby a pre-transplantation serum ferritin level measured up to 100 days prior to transplantation of patients with invasive fungal pneumonia (IFP) and non-fungal pneumonia (non-IFP) was compared. Patient records revealed 35 and 38 cases of IFP and non-IFP, respectively. In risk evaluation for IFP, age, gender, HLA status, conditioning regimen, smoking history, and underlying disease were not significantly different among groups (p>0.05). However, performance status (Karnofsky) was significantly lower in patients with IFP (p<0.05). The median ferritin levels were 1,705 ng/ml (41-7198) in the IFP group and 845 ng/ml (18-7099) in non-IFP group and the difference was found statistically significant (p=0.001). Elevated pretransplant serum ferritin level is associated with IFP in patients that underwent alloHSCT, in particular when values exceed 1550 ng/ml., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Uric acid (UA) acts as a richly available water-soluble antioxidant, contributing to approximately two-thirds of the overall free-radical-scavenging activity in human serum. It is discharged from damaged cells during the preparation for allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study assessed how pretransplantation uric acid levels influence survival and mortality in allo-HSCT patients. In a retrospective analysis of 267 patients with hematologic diseases who underwent allo-HSCT, uric acid levels were documented on the day of allo-HSCT (day 0). Patients were divided into two cohorts based on their pretransplant uric acid levels: those at or below 4.4 mg/dL and those above 4.4 mg/dL. Among them, 153 (57.3%) were male, and 114 (42.7%) were female, with a median age of 31 years (ranging from 13 to 66). Those with serum uric acid levels of 4.4 mg/dL or lower exhibited notably poorer overall survival (OS) and disease-free survival (DFS) compared to those surpassing 4.4 mg/dL (p=0.032 and p=0.045, respectively). Our findings indicate an interrelation between low pretransplant serum uric acid levels and reduced survival rates in allo-HSCT patients. Further exploration into potential mechanisms, such as compromised antioxidative capacity in hypouricemia, may establish uric acid as a promising prognostic marker in allo-HSCT. [ABSTRACT FROM AUTHOR]

Inflammatory processes play an important role in the pathophysiology of cGVHD. Serum fibrinogen is a proinflammatory protein with a wide range of functions in inflammation. But its role in GVHD is unclear. The aim of this study was to evaluate the predictive impact of pre-transplantation fibrinogen levels on cGVHD in allo-HSCT recipients. We retrospectively analyzed 249 patients with hematologic diseases undergoing allo-HSCT from 10/10 HLA-matched donors. Serum high fibrinogen levels at the time of HSCT (day 0) were significantly associated with cGVHD development in univariate analyses (OR 2.01, p= 0.012) and multivariate analyses (OR 1.003, p= 0.037). There was no significant association between fibrinogen levels and overall survival, disease-free survival and, acute GVHD (p> 0.05). This is the first report demonstrating the association between high fibrinogen levels and increased cGVHD occurrence. Further studies are warranted and may identify the efficacy of fibrinogen as a predictive marker on cGVHD in allo-HSCT recipients. [ABSTRACT FROM AUTHOR]

Objective: The reactivation rate of dormant hepatitis B virus (HBV) in the liver is between 4.1% and 41.5% in immune-compromised patients. The disappearance of hepatitis B surface antibody (anti-HBs) can be an alarm for hepatitis B reactivation. In this study, the changes in serological status, reactivation rates, and antiviral prophylaxis rates were evaluated. Materials and Methods: A retrospective study was conducted involving patients who were followed up at Erciyes University HSCT Center between January 2018 and July 2019. The demographic data, type of hematological disease, pre- and post-transplant status of HBV, presence of antiviral prophylaxis, and frequency of hepatitis B flare were evaluated. Results: One hundred and seven patients were included in this study. The median follow-up duration was 18 months. New chemotherapy protocols were initiated in 36 patients due to progression and in 23 patients with a diagnosis of graft-versushost disease. Anti-HBs levels decreased in 60% of the patients, and anti-HBs levels decreased to below the protective level in 13% of the patients. Among the 107 patients, 38 had resolved hepatitis B infection before transplantation, and 20 and four of 18 patients (22%) who did not receive antiviral prophylaxis developed HBV seroconversion and hepatitis B flare. The median levels of anti-HBs titers after transplantation were 167 IU/L and 15 IU/L in groups that received and did not receive antiviral prophylaxis, respectively (p=0.028). Conclusion: Antiviral prophylaxis should be administered in patients positive for hepatitis B core antibody before hematopoietic stem-cell transplantation. Measuring HBV serological parameters at regular intervals is essential in the high-risk group. [ABSTRACT FROM AUTHOR]

Total body irradiation (TBI) combined with chemotherapy is widely used as a pretreatment regimen of bonemarrowtransplantation (BMT) in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transversemyelitis (ATM) is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spinal cord. In this paper, we presented an ATM attack developed after TBI in a patient with acute lymphoblastic leukemia (ALL) as it is a rarely seen case. [ABSTRACT FROM AUTHOR]