COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Assessment of metabolic syndrome parameters in pediatric acute lymphoblastic leukemia survivors.

Objective: This study aims to demonstrate the prevalence of metabolic syndrome parameters and to investigate their relationship with body mass index in pediatric acute lymphoblastic leukemia survivors. Methods: The cross-sectional study was conducted between January and October 2019 at the Department of Pediatric Hematology and comprised acute lymphoblastic leukemia survivors who had been treated between 1995 and 2016 and had been off treatment for at least 2 years. The control group included 40 healthy participants who were matched for age and gender. The two groups were compared in terms of various parameters (BMI [body mass index], waist circumference, fasting plasma glucose, HOMA-IR [Homeostatic Model Assessment-Insulin Resistance], etc.). Data were analyzed using Statistical Package for the Social Sciences (SPSS) 21. Results: Of the 96 participants, 56 (58.3%) were survivors and 40 (41.6%) were controls. Among the survivors, there were 36 (64.3%) men, whereas the control group had 23 (57.5%) men. The mean age of the survivors was 16.67 ± 3.41 years, whereas the mean age of the controls was 15.51 ± 4.2 years (P > 0.05). Multinomial logistic regression analysis showed that cranial radiation therapy and female gender were associated with overweight and obesity (P < 0.05). A significant positive correlation was found between BMI and fasting insulin, in survivors (P < 0.05). Conclusion: Disorders of the metabolic parameter were found to be more common among acute lymphoblastic leukemia survivors than among healthy controls.

The Relationship Between Premature Adrenarche and Platelet Aggregation

Objective: Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients. Methods: The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method. Results: There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001). Conclusion: Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.

Hematopoietic stem cell transplantation activities and HRQOL of refugee or asylum seeker children in Turkey: A multicenter study.

BACKGROUND: Refugee or asylum seekers (RAS) children are at increased risk of physical, developmental, and behavioral health issues. The aim of this study was to evaluate clinical and psychosocial outcomes of hematopoietic stem cell transplantation (HSCT) in RAS children and compare health-related quality of life (HRQOL) to those of Turkish peers. METHODS: This retrospective study included patients who underwent HSCT aged 0-18 years and completed 100-day post-transplant. The PedsQL 4.0 Generic Core Scale was used in children over 5 years old to compare HRQOL. RESULTS: A total of 166 RAS patients (M/F: 106 /60) underwent 174 HSCTs (six patients had two, and one had three HSCT) compared to 66 Turkish patients. The mean age of the patients in the RAS group was 7.8 ± 4.9 years and similar to controls. A total of 124 patients (75%) were from Syria, and 49 (25%) were from other countries in the Middle East and Africa. The cause of migration was war in 121 (74%) RAS patients. Complications of HSCT were no different between the groups. However, the rate of neutropenic sepsis was significantly higher in the RAS group (p = 0.004). The total scores of HRQOL were not different between RAS and controls. In the RAS group, ratings of social functioning were lower in patients with consanguinity or non-malignant disease or who had match-related donors. DISCUSSION: Identifying areas of difficulty in subscales of HRQOL may help physicians to classify patients who need additional supportive care. Regular monitoring and supporting physical needs may result in better functional outcomes after HSCT.

Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.

Thrombin generation in children with febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) is a common and serious complication in patients with leukemia. Hemostasis and inflammation are two interrelated systems in response to infection. We aimed to investigate the course of thrombin formation in febrile neutropenia attack of children with acute lymphoblastic leukemia (ALL). METHODS: Thrombin generation was monitored in children treated for ALL at diagnosis of febrile neutropenia (FN) (t < sub > 0 < /sub > ), at 48 < sup > th < /sup > hour of FN (t1) and after recovery from neutropenia (t < sub > 2 < /sub > ). RESULTS: Twenty-nine patients and 50 healthy children as control were enrolled into the study. Mean endogenous thrombin potential (ETP) and mean peak value of thrombin results at t < sub > 1 < /sub > were significantly higher than at t < sub > 0 < /sub > , t < sub > 2 < /sub > and control groups, respectively. A positive but statistically nonsignificant correlation between ETP values at t < sub > 1 < /sub > and duration of neutropenia was observed. CONCLUSION: Although thrombin generation is enhanced both due to chemotherapy or malignancy itself, our results revealed that thrombin formation also increased in neutropenic infection of children with leukemia.

Comparison of 2% Chlorhexidine Gluconate in 70% Alcohol and 10% Povidone-Iodine Used for Port Catheter Dressing Changes in Pediatric Hematology-Oncology Patients: A Prospective Observational Study.

OBJECTIVE: This study aimed to compare the effectiveness of 2% chlorhexidine gluconate in 70% alcohol with that of 10% povidone-iodine, for dressing changes in pediatric hematology-oncology patients with port catheters, in preventing catheter-related bloodstream infection (CRBSI). METHODS: In this prospective, multicenter, observational, and cross-sectional study, 45 patients (25 patients for chlorhexidine, 20 patients for povidone-iodine) with port catheters were evaluated from January 2018 to May 2019. The sociodemographic, clinical, and port catheter-related variables were evaluated. The mean age of the patients was 6.28 ± 4.58 years, and 60% of patients were female. RESULTS: Among the patients whose dressings were changed using 2% chlorhexidine gluconate in 70% alcohol, the mean number of dressing changes was 39.52 ± 29.7 and the rates of exit-site infection and CRBSI were 20% (2.37/1000 catheter-days) and 16% (1.90/1000 catheter-days), respectively. Among the patients whose dressings were changed using 10% povidone-iodine, the mean number of dressing changes was 48.0 ± 31.48 and the rates of exit-site infection and CRBSI were 15% (1.59/1000 catheter-days) and 10% (1.06/1000 catheter-days), respectively. None of the patients developed pocket infections. The rates of CRBSI and exit-site infections were not different between the 2 antiseptic solutions. CONCLUSION: This study found no differences between the effectiveness of 2% chlorhexidine in 70% alcohol and that of 10% povidone-iodine solution in preventing CRBSI. Therefore, both solutions can be used in dressing changes.

Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia.

BACKGROUND: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. PROCEDURE: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. RESULTS: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. CONCLUSION: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.

Role of a second transplantation for children with acute leukemia following posttransplantation relapse: a study by the Turkish Bone Marrow Transplantation Study Group.

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69-2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score <80 (HR = 3.2). Pediatric patients with AL who relapsed after their first alloHSCT may survive with a second alloHSCT. Disease status, conditioning intensity, donor type, and performance score at the second transplantation are the relevant risk factors. A score based on these factors may predict the results of the second transplantation.

Diferenciación entre linfadenopatía cervical benigna y maligna mediante ecografía en niños / Differentiation of benign from malignant cervical lymphadenopathy by ultrasonography in children

Introducción. Las causas más frecuentes de la linfadenopatía cervical son las afecciones inflamatorias y reactivas; solo unos pocos casos representan una patología seria. El objetivo fue evaluar la relación entre los hallazgos ecográficos y el diagnóstico histopatológico. Población y métodos. Este estudio retrospectivo abarcó la linfadenopatía cervical en los menores de 20 años seguidos en nuestro centro, entre enero de 2007 y diciembre de 2016. Según los informes anatomopatológicos, se dividió a los pacientes en dos grupos: benigno y maligno. Se compararon los resultados anatomopatológicos y los hallazgos ecográficos. Resultados. Después del análisis de los resultados histopatológicos y los hallazgos ecográficos, se incluyó a 107 pacientes con linfadenopatía cervical persistente (44 casos malignos; 63, benignos). La media de edad de los grupos maligno y benigno fue de 14 ± 6,1 años y de 11,9 ± 4,8 años, respectivamente. La presencia de vascularidad hiliar fue estadísticamente significativa (p < 0,0001) en la linfadenopatía benigna, mientras que el flujo periférico y la vascularidad mixta lo fueron (p < 0,05) en la linfadenopatía maligna. No se observó una diferencia significativa en el diámetro máximo (27,3 ± 11,1 mm y 29,8 ± 12,3 mm, respectivamente), pero sí en el diámetro mínimo entre los grupos benigno y maligno (13,7 ± 7,3 mm y 18,7 ± 8,8 mm, respectivamente). Conclusiones. Este estudio sugiere que existe una relación entre los hallazgos ecográficos y de la biopsia para la diferenciación entre la linfadenopatía benigna y maligna, en especial, en el patrón vascular intraganglionar y el hilio ganglionar.

Introduction. The most common causes of cervical lymphadenopathy (LAP) are inflammatory and reactive conditions; only a small proportion have serious pathology, such as malignancy. The objective of this study was to evaluate the relationship between USG findings and histopathological diagnosis of the cervical LAP. Population and Methods. This retrospective study comprised the cases of cervical LAP in patients aged under 20 years old followed in our center between January 2007 to December 2016. Based on pathology reports, we divided the patients into two groups: benign and malignant. Pathology results and USG findings were compared. Results. After the analyze of the histopathological results and USG findings, 107 patients with persistent cervical LAP (44 malignant; 63 benign) were included in the study. Mean age of malignant and benign group were 14 ± 6.1; 11.9 ± 4.8 years, respectively. Hilar vascularity for benign LAP was highly statistically significant (P < 0.0001) and peripheral flow and mixed vascularity for malignant LAP were also statistically significant (p < 0.05). There was not a significant difference in the maximum diameter (27.3 ± 11.1 mm and 29.8 ± 12.3 mm, respectively), however, there was a significant difference in the minimum diameter between benign and malignant groups (13.7 ± 7.3 mm and 18.7 ± 8.8 mm, respectively).Conclusions. The present study suggests that there is a relationship between US and biopsy findings for the differentiation of benign from malignant LAP, especially in terms of nodal hilus and intranodal vascular pattern.

Differentiation of benign from malignant cervical lymphadenopathy by ultrasonography in children. / Diferenciación entre linfadenopatía cervical benigna y maligna mediante ecografía en niños.

INTRODUCTION: The most common causes of cervical lymphadenopathy (LAP) are inflammatory and reactive conditions; only a small proportion have serious pathology, such as malignancy. The objective of this study was to evaluate the relationship between USG findings and histopathological diagnosis of the cervical LAP. POPULATION AND METHODS: This retrospective study comprised the cases of cervical LAP in patients aged under 20 years old followed in our center between January 2007 to December 2016. Based on pathology reports, we divided the patients into two groups: benign and malignant. Pathology results and USG findings were compared. RESULTS: After the analyze of the histopathological results and USG findings, 107 patients with persistent cervical LAP (44 malignant; 63 benign) were included in the study. Mean age of malignant and benign group were 14 ± 6.1; 11.9 ± 4.8 years, respectively. Hilar vascularity for benign LAP was highly statistically significant (P < 0.0001) and peripheral flow and mixed vascularity for malignant LAP were also statistically significant (p < 0.05). There was not a significant difference in the maximum diameter (27.3 ± 11.1 mm and 29.8 ± 12.3 mm, respectively), however, there was a significant difference in the minimum diameter between benign and malignant groups (13.7 ± 7.3 mm and 18.7 ± 8.8 mm, respectively). CONCLUSIONS: The present study suggests that there is a relationship between US and biopsy findings for the differentiation of benign from malignant LAP, especially in terms of nodal hilus and intranodal vascular pattern.

Introducción: Las causas más frecuentes de la linfadenopatía cervical son las afecciones inflamatorias y reactivas; solo unos pocos casos representan una patología seria.El objetivo fue evaluar la relación entre los hallazgos ecográficos y el diagnóstico histopatológico. Población y métodos: Este estudio retrospectivo abarcó la linfadenopatía cervical en los menores de 20 años seguidos en nuestro centro, entre enero de 2007 y diciembre de 2016. Según los informes anatomopatológicos, se dividió a los pacientes en dos grupos: benigno y maligno. Se compararon los resultados anatomopatológicos y los hallazgos ecográficos. Resultados: Después del análisis de los resultados histopatológicos y los hallazgos ecográficos, se incluyó a 107 pacientes con linfadenopatía cervical persistente (44 casos malignos; 63, benignos). La media de edad de los grupos maligno y benigno fue de 14 ± 6,1 años y de 11,9 ± 4,8 años, respectivamente. La presencia de vascularidad hiliar fue estadísticamente significativa (p < 0,0001) en la linfadenopatía benigna, mientras que el flujo periférico y la vascularidad mixta lo fueron (p < 0,05) en la linfadenopatía maligna. No se observó una diferencia significativa en el diámetro máximo (27,3 ± 11,1 mm y 29,8 ± 12,3 mm, respectivamente), pero sí en el diámetro mínimo entre los grupos benigno y maligno (13,7 ± 7,3 mm y 18,7 ± 8,8 mm, respectivamente). Conclusiones: Este estudio sugiere que existe una relación entre los hallazgos ecográficos y de la biopsia para la diferenciación entre la linfadenopatía benigna y maligna, en especial, en el patrón vascular intraganglionar y el hilio ganglionar.

Clinical Features and HSCT Outcome for SCID in Turkey.

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed. PURPOSE AND METHODS: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis. RESULTS: A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome. CONCLUSIONS: This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Posterior Reversible Encephalopathy Syndrome in a Normotensive Child after Allogeneic Hematopoietic Stem Cell Transplantation.

Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinicoradiological syndrome that is characterized by acute neurological symptoms such as headache, convulsion, visual disturbance, and altered consciousness. The characteristic magnetic resonance (MR) finding is vasogenic edema, predominantly in the subcortical areas of the posterior parietal and occipital lobes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. Herein, we described a rare case of PRES induced by cyclosporine (CsA) after an allogeneic hematopoietic stem cell transplantation (HSCT) from a sibling donor.

Elevated plasma asymmetric dimethylarginine levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction.

OBJECTIVES: Beta-thalassemia major is associated with the increased risk of cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) has been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. In this study, we aimed to investigate circulating ADMA concentrations in children with beta-thalassemia major. METHODS: Thirty-one beta-thalassemia major children aged between 4 and 16 year old and age, gender-matched 36 healthy controls were enrolled in the study. Plasma ADMA was measured along with the soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and Pentraxin-3. RESULTS: Age, gender and body mass index were similar in two groups. Plasma ADMA, sVCAM-1, and sICAM-1 measurements were significantly higher in beta-thalassemia major patients than the control group (p < 0.004 for ICAM-1, p < 0.001 for other parameters). There were positive significant correlations between ADMA, sVCAM-1 and sICAM-1 (r = 0.437, p < 0.001; r = 0.544, p < 0.001; r = 0.405, p < 0.001, respectively) in the whole group. DISCUSSION: The findings of the current study show us that increased plasma ADMA levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction and may play a role in the development of premature atherosclerosis in beta-thalassemia major patients.

Heavy metal levels in patients with ineffective erythropoiesis.

OBJECTIVES: Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS: Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls. RESULTS: Blood samples were obtained from 68 patients (51 patients with TM, 8 with TI, 9 with CDA), and a control group that included 65 volunteers. Patients with TM were found to have lower Al, Pb, and Zn, and higher Cd levels compared with the control group. The patients treated with deferasirox were further analyzed and Pb and Zn levels were found lower compared with the control group. DISCUSSION: Patients with TM had tendency to have elevated levels of plasma cadmium; however, the median level was not at a toxic level. Increased metal-ion transporter 1 activity may cause heavy metal accumulation, but deferasirox chelation may be protective against heavy metals besides iron.

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 106 CD 34+ cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor.

Generation of Platelet Microparticles after Cryopreservation of Apheresis Platelet Concentrates Contributes to Hemostatic Activity.

OBJECTIVE: In the last decade, substantial evidence has accumulated about the use of cryopreserved platelet concentrates, especially in trauma. However, little reference has been made in these studies to the morphological and functional changes of platelets. Recently platelets have been shown to be activated by cryopreservation processes and to undergo procoagulant membrane changes resulting in the generation of platelet-derived microparticles (PMPs), platelet degranulation, and release of platelet-derived growth factors (PDGFs). We assessed the viabilities and the PMP and PDGF levels of cryopreserved platelets, and their relation with thrombin generation. MATERIALS AND METHODS: Apheresis platelet concentrates (APCs) from 20 donors were stored for 1 day and cryopreserved with 6% dimethyl sulfoxide. Cryopreserved APCs were kept at -80 °C for 1 day. Thawed APCs (100 mL) were diluted with 20 mL of autologous plasma and specimens were analyzed for viabilities and PMPs by flow cytometry, for thrombin generation by calibrated automated thrombogram, and for PDGFs by enzyme-linked immunosorbent assay testing. RESULTS: The mean PMP and PDGF levels in freeze-thawed APCs were significantly higher (2763±399.4/µL vs. 319.9±80.5/µL, p<0.001 and 550.9±73.6 pg/mL vs. 96.5±49 pg/mL, p<0.001, respectively), but the viability rates were significantly lower (68.2±13.7% vs. 94±7.5%, p<.001) than those of fresh APCs. The mean endogenous thrombin potential (ETP) of freeze-thawed APCs was significantly higher than that of the fresh APCs (3406.1±430.4 nM.min vs. 2757.6±485.7 nM.min, p<0.001). Moreover, there was a significant positive poor correlation between ETP levels and PMP levels (r=0.192, p=0.014). CONCLUSION: Our results showed that, after cryopreservation, while levels of PMPs were increasing, significantly higher and earlier thrombin formation was occurring in the samples analyzed despite the significant decrease in viability. Considering the damage caused by the freezing process and the scarcity of evidence for their in vivo superiority, frozen platelets should be considered for use in austere environments, reserving fresh platelets for prophylactic use in blood banks.

Is one-size-fits-all strategy adequate for platelet storage?

BACKGROUND: Platelet suspensions (PSs) are stored at room temperature. However, recent reports show that PSs stored at 4 °C possess superior hemostatic properties. We compared the viabilities and thrombin generation capacities of PSs stored either at 4 °C or 22 °C hours. MATERIALS AND METHODS: Twenty units of apheresis derived platelets (ADPs) from 20 male donors and 20 units of random platelet suspensions (RPSs) from another 20 male donors were obtained. Half of the ADPs and half of the RPSs (10 units/per group) were stored at 4 °C, the other halves of ADPs and RPSs (10 units/per group) were stored in agitators at 22 °C for 48 hours. The flow cytometric viability tests and thrombin generation tests of the PSs were assessed. RESULTS: The viabilities of both ADPs and RPSs group platelets, stored either at 4 °C or 22 °C for 48 hours, were not statistically significantly different. The ADPs and RPSs stored at 4 °C generated significantly higher peak thrombin levels than the platelets stored at 22 °C. Moreover, the ADPs group stored at 4 °C showed significantly shorter time to thrombin generation and reach peak levels. CONCLUSION: The PSs stored at 4 °C showed higher and faster thrombin generation capacities than the room temperature PSs. Given the superior hemostatic properties of refrigerated platelets, creating different storage temperature capabilities for specific transfusion purposes may be a prudent approach, especially for improving the outcome of bleeding trauma casualties.