Adjuvant Corticosteroid Therapy in Hepatosplenic Candidiasis-Related Iris

Candida infections are the most frequent infections in neutropenic patients. Hepatosplenic candidiasis (HSC) is a part of disseminated Candida infection that occurs most commonly in patients with hematologic malignancies treated with chemotherapy and requires protracted antifungal therapy. During invasive mycosis with rapid resolution of immunosuppression, immune reconstitution inflammatory syndrome (IRIS) which mimics treatment failure, drug toxicity or breakthrough infections may occur. Manifestation period, histopathologic findings and favorable effect of steroids to its inflammatory symptoms strongly suggest that HSC belongs to the invasive fungal infection induced IRIS. We present a child with B cell-acute lymphoblastic leukemia who developed HSC and addition of corticosteroid therapy to antifungal treatment achieved rapid resolution of the clinical symptoms and laboratory findings

Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita–like phenotypes

This research was originally published in Blood Online. Tummala, H., et al. (2018). "Homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita–like phenotypes." Blood 132(12): 1349-1353. Title. Blood. Prepublished Sept 20 2018; DOI https://doi.org/10.1182/blood-2018-03-837799Dyskeratosis congenita (DC) and its severe form, Hoyeraal-Hreidarsson syndrome (HHS), are rare and have life-threatening failure of hematopoiesis. Typically, DC patients present with disease features such as nail dystrophy, oral leukoplakia, and abnormal skin pigmentation along with peripheral pancytopenia and marrow hypoplasia with strong predisposition to cancer.1 In DC, hematopoietic failure occurs due to critical shortening of telomeres,2,3 which enhances the DNA damage response4,5 and leads to premature senescence of hematopoietic stem cellsMedical Research Council (grant MR/P018440/1), Bloodwise (grant 14032), and Children with Cancer UK (grant 2013/144)

Relationship Between the Levels of Holotranscobalamin and Vitamin B12 in Children.

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B12 in children and to identify a cutoff cobalamin values according to holoTC. One hundred and fifty-five children were enrolled into the study. All children were evaluated for hemoglobin, vitamin B12, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B12 level (≤200 pg/mL, group I) and normal vitamin B12 (>200 pg/mL, group II). Serum vitamin B12, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B12 (group I) the mean holoTC was 21.74 ± 1.14 pmol/L. In 54 children with normal vitamin B12 (group II) mean holoTC was 44.0 ± 2.7 pmol/L (p < 0.01). A ROC curve analysis was performed to delineate the optimum cut-off point for vitamin B12 level and it was found to be 165 pg/mL with a sensitivity of 70% and specificity of 74%; the area under curve was 0.783 (p < 0.01). Our study displayed a positive correlation between vitamin B12 and holoTC, and defined an optimum cutoff value for vitamin B12 as 165 pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed

BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole

Relationship Between the Levels of Holotranscobalamin and Vitamin B-12 in Children

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B-12 in children and to identify a cutoff cobalamin values according to holoTC. One hundred and fifty-five children were enrolled into the study. All children were evaluated for hemoglobin, vitamin B-12, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B-12 level (<= 200 pg/mL, group I) and normal vitamin B-12 (> 200 pg/mL, group II). Serum vitamin B-12, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B-12 (group I) the mean holoTC was 21.74 +/- 1.14 pmol/L. In 54 children with normal vitamin B-12 (group II) mean holoTC was 44.0 +/- 2.7 pmol/L (p < 0.01). A ROC curve analysis was performed to delineate the optimum cut-off point for vitamin B-12 level and it was found to be 165 pg/mL with a sensitivity of 70\% and specificity of 74\%; the area under curve was 0.783 (p < 0.01). Our study displayed a positive correlation between vitamin B-12 and holoTC, and defined an optimum cutoff value for vitamin B-12 as 165 pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study

Background: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. Materials and Methods: In this multicenter retrospective study. 51 pediatric patients with leukemia. 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combi-nation with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links lww.com/JPHO/A541). Results: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus. Sixteen patients received single-agent. 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died. 29 of the CNSFI episodes recovered with a 20% neurological sequelae. Conclusion: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes

CANDIDA ASSOCIATED BLOODSTREAM INFECTIONS IN PEDIATRIC HEMATOLOGY PATIENTS: SINGLE CENTER EXPERIENCE

Background and Objectives: Candida-associated bloodstream infections are frequent and potentially life-threatening conditions in hematology patients. The aim of this study is to evaluate the characteristics, risk factors, and outcome of Candida-associated bloodstream infections in children with hematological diseases at a children’s hospital. Methods: The medical records of the patients with hematological diseases and hematopoietic stem cell transplantation (HSCT) recipients who were diagnosed as Candida-associated bloodstream infection between February 2010 and February 2014 were reviewed retrospectively. Results: Thirty episodes of candidemia involving 26 patients (38% female, and 62% male) with median age of 7 years (range; 1 to 17) were noted. Infections with non-albicans Candida spp. occurred more frequently (63%) and C. krusei was the predominant microorganism among non-albicans Candida spp. (37%). Candida albicans was isolated from 11 of the 30 episodes (37%). Twenty-three of the patients (88%) had central venous catheter (CVC) prior to candidemia, and they were removed in 16 of the 30 episodes (53%). Isolated Candida spp, underlying disease and status of the disease, presence of mucositis, neutropenia, using of broad spectrum antibiotics, corticosteroids or total parenteral nutrition were not identified as predictors of outcome. However patients whose CVCs had not been removed were more likely to die than those whose had been removed (54% vs. 6%, respectively; p=0.012). Conclusions: Candida-associated bloodstream infections in children with hematological diseases and HSCT recipients were common particularly in patients with CVCs. Beside appropriate antifungal therapy, CVC removal improves the outcome of candidemia in children with hematological disease

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were 3 to 5xupper limit of normal (ULN) in 2 patients, 5 to 10xULN in 2 patients, and >10xULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed