Clinical features and risk factors of hepatic sinusoidal obstruction syndrome in children after hematopoietic stem cell transplantation: A single-center experience.

Hepatic sinusoidal obstruction syndrome (SOS) is an illness with serious life effects that develops after hematopoietic stem cell transplantation (HSCT). We investigated the risk factors and clinical features of hepatic SOS in children following HSCT in 210 children who underwent allogeneic or autologous HSCT between 2009 and 2021 were analyzed in the context of SOS. The syndrome developed in 22 (10.4%) patients:frequently in neuroblastoma [24% (5/21)], hemophagocytic lymphohistiocytosis [57% (4/7)], and thalassemia major [22% (7/31)]. The median time from HSCT to diagnosis was 16 (6-38) days. Severe disease occurred in 8 (36%) patients, and mild/moderate in 14 (64%) and 4 patients died (18%). In univariate analyses, patient's age ≤ 2 years [odds ratio (OR)= 3.043, P = 0.028], pretransplant AST and ALT levels > 100 U/L (OR=3.576, P = 0.045), and chemotherapy/radiotherapy to abdomen before transplantation (OR = 3.162, P = 0.044) were determined as risk factors. In multivariate analysis, pre-transplant AST and ALT levels > 100 U/L (OR = 16.04, P = 0.010) and ferritin levels over 1000 mg/dl (OR=5.15, P = 0.047) were significant. The only independent risk factor on mortality was the age ≤ 2 years (P = 0.001). Although our study confirmed several risk factors for SOS, we failed to achieve some well-known risk factors. Precautions should be taken considering the factors affecting liver function before transplantation and the risk of SOS in infants receiving chemotherapy and radiotherapy before transplantation, such as neuroblastoma in which comparable results in respect to the chemotherapy only. The risk factors should be fully elucidated in multicenter studies to improve preventive and therapeutic strategies.

Hodgkin's lymphoma associated with paraneoplastic cerebellar degeneration in children: a case report and review of the literature.

Paraneoplastic cerebellar degeneration (PCD) can occur severely and appear as subacute cerebellar syndrome. PCD may be associated with small cell lung cancer, adenocarcinoma, breast cancer, ovarian carcinoma, and Hodgkin's lymphoma. An 11-year-old male was admitted with acute cerebellar ataxia, dysarthria, and diplopia. Mediastinal conglomerated lymph nodes were depicted in a chest computed tomography (CT) examination, and diagnosis of stage IV Hodgkin's lymphoma was obtained after a lymph node biopsy. The antibodies against Purkinje cells (anti-Tr antibody) were positive immunohistochemically. Thus, paraneoplastic cerebellar degeneration depending on Hodgkin's disease was diagnosed. Despite the completion of chemotherapy, neurological recovery was not observed in the patient and plasmapheresis with immunoadsorption, and intravenous immunoglobulin (IVIG) was performed. Truncal ataxia, gait disturbance, and tremors decreased. Consequently, we thought that plasmapheresis with the immunoadsorption method and IVIG therapy might be a treatment option for cerebellar ataxia caused by a mechanism of immune ancestry.

Therapeutic plasma-exchange in hematologic disease: results from a single center in Eastern Anatolia.

Therapeutic plasma-exchange (TPE) is used as primary and adjunctive therapy in treatment of several hematologic diseases. We retrospectively evaluated the results of TPE in hematologic diseases during 2008-2012. A total of 301 TPE procedures were performed in 44 patients (19 male and 25 female, with mean age of 50.6±15years). Fifteen of 44 patients had thrombotic thrombocytopenic purpura (TTP), 14 patients had HELLP syndrome (Hemolysis Elevated Liver enzymes, Low Platelet count), 10 patients had multiple myeloma-hyperviscosity and the rest five patients had snake bite. Fresh frozen plasma (FFP) was used as replacement fluid. Complete response (CR) was achieved on 13 patients (87%) in primarily TTP. CR was achieved in all other three diseases. Total complications were detected in 8.1% of the TPE procedures. Adverse events (AEs), were seen in 5.4% of all procedures. None of the patients died from any complication. AE occurred in 4% (Grade-I), 1% (Grade-II), and 0.3% (Grade-III) of the procedures. The most common AE were nausea/vomiting, hypotension, pruritus and abdominal pain. TPE is effectively and safely carried out in our center in hematologic diseases.

Prevalence of Demodex folliculorum and Demodex brevis in childhood malnutrition and malignancy.

BACKGROUND: Hair follicle mites, Demodex folliculorum and Demodex brevis, are known to accompany immune-deficiency states, however no study so far has investigated their presence in malnutrition. In this study we aimed to determine the prevalence of those mites in childhood malnutrition, malignancy and risk factors. METHODS: One hundred children with malnutrition, 31 children with malignancy and 63 children without any chronic disease and infection were included in this study. History, physical examination, anthropometric measurements and routine laboratory findings were recorded. Demodex spp. were investigated by standard superficial skin biopsies. RESULTS: Demodex was found in 25 patients (25%), 10 patients (32.3%), and one patient (1.6%) among malnutrition, malignancy, and control groups, respectively (P = 0.001). By using multilogistic regression binary method, it was found that malnutrition, malignancy and low socioeconomic level increased the risk 17.37 times (P = 0.006), 27.29 times (P = 0.002), and 2.3 times (P = 0.037), respectively. Of 22 children who were evaluated after 6 months, 13 (59.1%) were negative for Demodex. In 11 (84.6%) of those 13, nutritional status was improved. CONCLUSION: Demodex was detected in approximately in one-quarter and one-third of children with malnutrition and malignancy, respectively. Eliminating the cause of immunosuppression, such as poor nutritional status, seems also to be an effective method for eliminating Demodex.

Thromboembolism in Children.

OBJECTIVE: To study pediatric patients who were diagnosed with thrombosis between January 2009 and March 2020. METHODS: Patients were evaluated with respect to thrombophilic risk factors, localization of the thrombus, response to treatment, and recurrence rates during the last 11 y. RESULTS: Among 84 patients, 59 (70%) had venous thrombosis and 20 (24%) had arterial thrombosis. The number of documented thrombosis amongst hospitalized children in authors' hospital has increased over the years. It has been observed that the annual incidence of thromboembolism has increased after 2014. Thirteen patients were recorded between 2009 and 2014 and 71 patients between 2015 and 2020 (until March 2020). Exact thrombosis localization could not be detected in 5 patients. The median age of patients was 8 ± 5.95 (range 0-18). Fourteen children (16.9%) had a history of familial thrombosis. Genetic and/or acquired risk factors were detected in 81 (96.4%) of the patients. Overall, 64 patients (76.1%) had acquired risk factors such as infection (20.2%), catheterization (13.1%), liver disease (11.9%), mastoiditis (8.3%), liver transplantation (6%), hypoxic-ischemic encephalopathy (4.8%), dehydration (3.6%), trauma (3.6%) and cancer (2.4%). As genetic risk factors, the most common genetic mutations were PAI-1 4G>5G, MTHFR C677T, and MTHFR A1298C mutations. Twenty-eight (41.2%) patients had at least one genetic thrombophilic mutation. At least one homozygous mutation in 37 patients (44%) and at least one heterozygous mutation in 55 patients (65.4%) were detected. CONCLUSIONS: The annual incidence of thrombosis has increased over the years. Genetic predisposition and acquired risk factors play an important role in etiology, treatment, and follow-up in children with thromboembolism. Especially, genetic predisposition is common. Thrombophilic risk factors should be investigated and optimal therapeutic and prophylactic measures should be promptly taken in children with thrombosis.

Rare coagulation disorders: a retrospective analysis of 156 patients in Turkey.

OBJECTIVE: To retrospectively evaluate the clinical findings, laboratory data, management, and outcome in a group ofTurkish children diagnosed with rare coagulation deficiencies (RCDs) between January 1999 and June 2009. MATERIAL AND METHODS: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis-Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for standardized data collection and sent it to participatinginstitutions. RESULTS: In total, 156 patients from 12 pediatric referral centers were included in the study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24 [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in the patients was epistaxis, followed by ecchymosis, and gingival bleeding. CONCLUSION: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP) and tranexamic acid werethe most commonly used treatments. We think that prophylactic treatment used for hemophilia patients should beconsidered as an initial therapeutic option for patients with rare factor deficiencies and a severe clinical course, and forthose with a factor deficiency that can lead to severe bleeding.

Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy.

Although the anthracyclines have gained widespread use in the treatment of childhood hematological malignancies and solid tumors, cardiotoxicity is the major limiting factor in the use of anthracyclines. The aim of this study was to assess the mitral annular displacement by tissue tracking in pediatric malignancy survivors who had been treated with anthracycline groups chemotheraphy and compare with the tissue Doppler and conventional two dimensional measurements and Doppler indices.In this study, 32 pediatric malignancy survivors and 22 healthy children were assessed with 2D, colour-coded echocardiography. Left ventricular ejection fraction, fractional shortening, stroke volume, cardiac output, cardiac index and diastolic functions were measured. All subjects were assessed with tissue Doppler echocardiography, mitral annular displacements, and also with tissue tracking method.We detected that peak velocity of the early rapid filling on tissue Doppler (E') was lower (p < 0.05) and the ratio of early peak velocity of rapid filling on pulse Doppler to tissue Doppler (E/E') values were statistically higher in patient group than control group (p < 0.05). Myocardial performance index values were also higher in patient group than the control group (p < 0.01). It appears that MPI is a useful echocardiograghic method than tissue tracking of mitral annular displacement in patients with pediatric cancer survivors who had subclinical diastolic dysfunction.

Clinical and Imaging Findings in Childhood Posterior Reversible Encephalopathy Syndrome.

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is characterized by typical radiologic findings in the posterior regions of the cerebral hemispheres and cerebellum. The symptoms include headache, nausea, vomiting, visual disturbances, focal neurologic deficits, and seizures. The aim of this study is to evaluate the clinical and radiological features of PRES in children and to emphasize the recognition of atypical features. MATERIALS & METHODS: We retrospectively examined 23 children with PRES from Mar 2010-Apr 2015 in Inonu University Turgut Ozal Medical Center in Turkey. We compared the clinical features and cranial MRI findings between underlying diseases of PRES. RESULTS: The most common precipitating factors were hypertension (78.2%) and medications, namely immunosuppressive and antineoplastic agents (60.8%). Manifestations included mental changes (100%), seizures (95.6%), headache (60.8%), and visual disturbances (21.7%) of mean 3.6 (range 1-10) days' duration. Cranial magnetic resonance imaging (MRI) showed bilateral occipital lesions in all patients, associated in 82.6% with less typical distribution of lesions in frontal, temporal or parietal lobes, cerebellum, corpus callosum, basal ganglia, thalamus, and brain stem. Frontal involvement was predominant, observed in 56.5% of patients. Clinical recovery was followed by radiologic resolution in all patients. CONCLUSION: PRES is often unsuspected by the clinician, thus radiologists may be the first to suggest this diagnosis on an MRI obtained for seizures or encephalopathy. Atypical MRI finding is seen quite often. Rapid diagnosis and treatment are required to avoid a devastating outcome.

Relationship between activation and apoptosis in platelets.

Phosphatidylserine (PS) externalization is a marker for the nucleated cell apoptosis, and refers cellular activation rather than apoptosis in platelets. On the other hand, several similarities exist between platelet activation and apoptosis in nucleated cells. Herewith we investigated the relationship between platelet activation and platelet apoptosis. Platelets isolated from fresh blood of 22 healthy volunteers were incubated with and without calcium ionophore A23187. Platelet activation was evaluated with CD62P and CD63 antibodies, whereas apoptosis with intracellular anti caspase 3-antibody and JC-1 cationic dye. In order to detect PS externalization we used Annexin V by flow cytometry at the beginning, 20th min and 5th hours of the incubation, respectively. There were positive correlations between caspase-3 activation and PS externaization, ∆Ψm depolarization, CD63, and also between PS externaization and CD62P in incubations with A23187 at 5th hours of incubations. These results suggest that there is a relationship between activation and apoptosis in platelets, and platelet activation may progress to platelet apoptosis.

Degradation of vincristine by myeloperoxidase and hypochlorous acid in children with acute lymphoblastic leukemia.

Vincristine (VCR) is an effective drug against acute lymphoblastic leukemia (ALL), many solid tumors, but not acute myeloid leukemia. It has been hypothesized that resistance of myeloblasts to VCR is related to myeloperoxidase (MPO) and production of hypochlorous acid (HOCl). We investigated the relationship between VCR degradation and MPO expression and serum HOCl concentrations in pediatric patients with ALL, lymphoma and solid tumors. We studied the sera from 43 children, of which 23 were newly diagnosed and as yet untreated cancer patients, 10 on chemotherapy and 10 healthy control subjects. Patients' sera were incubated with VCR alone or in the presence of taurine (T) or acetaminophen (APAP) and post-incubation VCR and HOCL concentrations were measured. Significant correlations between serum MPO expression, HOCl concentrations and VCR degradation were seen. In the chemotherapy group, MPO-positive patients produced high levels of HOCl and reciprocally low post-incubation VCR levels. HOCl and VCR concentrations in this group were significantly different than other groups studied. Both APAP and T inhibited VCR degradation in the sera of the chemotherapy group but not to the same degree. The effects seen here were consistent for both ALL and the lymphoma/solid tumor cases. Our results indicate that HOCl can increase VCR degradation in vitro in the serum and this effect is significantly more pronounced in pediatric patients undergoing chemotherapy.

[Evaluation of the intestinal parasitic infections in children patients with cancer]. / Kanser Hastasi Çocuklarda Bagirsak Paraziti Enfeksiyonlarinin Degerlendirilmesi.

OBJECTIVE: We aimed to determine the prevalence and type of the intestinal parasites in healthy, cancer and survivor children after cancer therapy, and to evaluate whether there are any differences in incidence and types of parasites during their neutropenic period. METHODS: Three different patient groups were formed. Group I and Group II were immune deficient patients with hematologic malignancy or solid tumors, and Group I were receiving intensive chemotherapy and had absolute neutrophil count less than 1000/mm³. Group II were receiving maintenance chemotherapy and had normal absolute neutrophil counts. One hundred and seventy two patients, who did not receive chronic immune suppressant treatment and who did not have immune deficiency were chosen among the patients admitted to pediatric hematology outpatient clinic. Parasitic evaluation of stools was performed on three consequtive days. RESULTS: Prevalence of parasite in Group I patients was significantly higher than other groups. The most commonly detected parasite in all groups was Giardia intestinalis. The presence of parasite in patients with absolute neutrophil counts below 1000/mm³ was found to be significantly higher than in patients with absolute neutrophil counts above 1000/mm³. CONCLUSION: Parasitic infections should not be ignored when these types of patients present with infection findings.

Presence of a D8/17 B lymphocyte marker and HLA-DR subgroups in patients with rheumatic heart disease.

OBJECTIVE: The aim of our study was to investigate the association of HLA antigens and a non-HLA protein D8/17 with rheumatic heart disease and its pattern of cardiac involvement. METHODS: This cross- sectional observational study included 35 children and 12 adult patients who have rheumatic heart disease and 35 healthy children and 12 healthy adult controls. After physical examination, all patients and control group members were evaluated with 2D and color-coded echocardiography. B- lymphocyte D8/17 expression was tested by a flow cytometry assay. HLA genotyping was performed using polymerase chain reaction sequence-specific primers. In statistical analysis, Chi-square, unpaired t and Mann-Whitney U tests were used for comparison groups. RESULTS: The percentage of the D8/17-expressing B lymphocytes of the patient group was significantly higher than of the control group (77.3±15.6% vs. 67.7±20.0%, p=0.013). When compared with the control group, the HLA DRB5 (38.6% vs. 13.6%, p=0.007) and HLA DRB1*15 (31.8% vs. 9.0%, p=0.008) expression levels of the patient group were significantly higher and the DRB4 expression of the patient group was significantly lower (29.5% vs. 50.0%, p=0.049). CONCLUSION: Our findings support the association between HLA Class 2 subgroups and rheumatic heart disease, and an association between D8/17 expression and rheumatic heart disease. Further studies including higher number of patients and control group members should be performed for the confirmation of our results.

Neutropenic enterocolitis (typhlitis) associated with infectious mononucleosis.

Neutropenic enterocolitis (typhlitis) is an unusual acute complication of neutropenia, most often associated with leukaemia and lymphoma and characterized by segmental caecal and ascending colonic ulceration that may progress to necrosis, perforation, and septicaemia. We present a unique case of an 8-year-old girl with recently diagnosed infectious mononucleosis having findings consistent with typhlitis on abdominal CT.

Malignant melanoma of the soft parts showing calciphylaxis.

Calciphylaxis is a poorly understood and highly morbid syndrome of vascular calcification and skin necrosis. Hypercalcemia, hyperphosphatemia, and secondary hyperparathyroidism are the factors implicated in the pathogenesis of calciphylaxis, which is generally identified in patients with hyperparathyroidism secondary to end-stage renal disease. It has also been observed in primary hyperparathyroidism, end-stage liver disease, and rheumatoid arthritis, in the absence of renal disease. There are few case reports of calciphylaxis occurring in hypercalcemia of malignancy. An unusual case is reported of calciphylaxis associated with malignant melanoma of the soft parts in the absence of renal or parathyroid disease. This is the first reported case of this soft tissue sarcoma showing calciphylactic changes.

Analysis of pediatric thrombotic patients in Turkey.

This study analyzes the data of thrombotic children who were followed up in different pediatric referral centers of Turkey, to obtain more general data on the diagnosis, risk factors, management, and outcome of thrombosis in Turkish children. A simple two-page questionnaire was distributed among contact people from each center to standardize data collection. Thirteen pediatric referral centers responded to the invitation and the total number of cases was 271. All children were diagnosed with thromboembolic disease between January 1995 and October 2001. Median age at time of first thrombotic event was 7.0 years. Of the children 4% of the cases were neonates, 12% were infants less than 1 year old, and 17% were adolescents. Thromboembolic event was mostly located in the cerebral vascular system (32%), deep venous system of the limbs, femoral and iliac veins (24%), portal veins (10%), and intracardiac region (9%). Acquired risk factors were present in 86% of the children. Infection was the most common underlying risk factor. Inherited risk factors were present in 30% of the children. FVL was the most common inherited risk factor. Acquired and inherited risk factors were present simultaneously in 19% of the patients. Eleven children had a history of familial thrombosis. Due to the local treatment preferences, the treatment of the children varied greatly. Outcome of the 142 patients (52%) was reported: 88 (62%) patients had complete resolution, 47 (33%) had complications, 12 (9%) had recurrent thrombosis, and 34 (24%) died. Three children (2.1%) died as a direct consequence of their thromboembolic disease. The significant morbidity and mortality found in this study supports the need for multicentric prospective clinical trials to obtain more generalizable data on management and outcome of thrombosis in Turkish children.