The evaluation of Candida-related central line-related bloodstream infections in pediatric cancer patients: A pre- and post-intervention study.

Aim/Objections: The purpose of this study was to assess the efficacy of a central line maintenance bundle in preventing catheter-related (implanted venous access devices, port) Candida bloodstream infections. Methods: The study encompassed two distinct time periods, namely, pre-bundle and bundle. The number of catheter-related bloodstream infections (CRBSI) episodes per catheter days for each timeframe was determined. Findings/Results: Upon implementation of the central line bundle, the rate of CRBSI reduced significantly from 4.27 per 1000 central line days in the pre-bundle period to 1.0 per 1000 central line days in the bundle period (p < .001). Discussion: Using a central line bundle to avoid CRBSIs in pediatric cancer patients with ports led to a significant decrease in Candida species-related CRBSIs.

A Neonatal Case of Infantile Malignant Osteopetrosis Presenting with Thrombocytopenia and Hypotonicity: A Novel Mutation in Chloride Voltage-Gated Channel 7 Gene.

Autosomal recessive osteopetrosis is also known as infantile malignant osteopetrosis (IMO). The clinical course is often serious and if left untreated, it is fatal in the 1st year of life. Diagnosis is challenging and often delayed or misdiagnosed. Herein, we present an infant girl who was diagnosed with IMO during evaluations for her hypotonicity and thrombocytopenia. A novel mutation of the chloride voltage-gated channel 7 (CLCN7) gene was also reported. A 10-day-old female patient was referred to our hospital for evaluation of hypotonicity. Her physical examination was normal, other than hypotonicity. Laboratory analysis revealed thrombocytopenia and hypocalcemia. In the progress, while she was followed in outpatient clinic, hepatosplenomegaly was detected at the age of 3 months. IMO was suspected with the findings of hepatosplenomegaly, cytopenia, hypocalcemia, difficulty of obtaining bone marrow, peripheral smear findings, and hearing loss. The X-ray of the bones was consistent with IMO. A novel pathogenic homozygous c.1504>T (p.Arg502Trp) mutation in CLCN7 gene was revealed. IMO is a rare disorder and it is important to differentiate this entity for better clinical outcome. The presence of neurological and hematological findings, organomegaly, hearing loss, and vision disorders must attract attention to IMO.

Assessment of clinical characteristics and treatment outcomes of pediatric patients with intracardiac thrombosis: a single-center experience.

The prevalence of intracardiac thrombus (ICT) is gradually increasing, though it is rare among children. Data related to the occurrence of ICT among children are limited, and treatment recommendations have been made utilizing adult guidelines. The primary objective of this study is to determine associated factors, management, and outcomes of intracardiac thrombosis in children. Between January 2013 and January 2020, patients diagnosed with ICT at the Pediatric Hematology-Oncology and Pediatric Cardiology departments in our hospital were included in the study. Demographic characteristics, clinical and laboratory findings, treatment protocols, and outcomes were analyzed retrospectively. The median age at diagnosis was 10.5 months (2 days to 14.5 years), and the median follow-up period was 6.5 months (1 month to 3.1 years). The most common primary diagnoses of the patients, in order of frequency, were heart disease (n: 8), metabolic disease (n: 3), prematurity and RDS (n: 3), burns (n: 2), pneumonia (n: 2), and asphyxia (n: 2). CVC was present in 19/23 of the patients. The reasons for CVC insertion were the need for plasmapheresis in one patient with a diagnosis of HUS and the need for well tolerated vascular access because of long-term hospitalization in others. LMWH was administered to all patients as first-line therapy. Complete response was achieved in 19 (79%) of 24 patients and 4 patients (16.6%) were unresponsive to medical treatment. It was found out that the thrombus location, type, sepsis, and hemoculture positivity, as well as the presence of CVC, had no impact on treatment response (chi-square P = 0.16, 0.12, 0.3, 0.49, 0.56). Moreover, no correlation was determined between thrombus size and treatment response (Mann Whitney U test P = 0.47). The mortality rate was determined to be 12.5% (3/24). Spontaneous occurrence of ICT is rare in childhood, without any underlying primary disease or associated factor. The presence of CVC, sepsis, and heart disease are factors associated with ICT. The success rate is increased with medical treatment. There was no significant difference in treatment response between the newborn and 1 month to 18-year-old patient group. It has been demonstrated that thrombus size, type, localization; sepsis, and hemoculture positivity had no impact on the treatment response.

Evaluation of renal effects of liposomal amphotericin B in children with malignancies with KDIGO and RIFLE criteria.

BACKGROUND: Amphotericin B is a broad-spectrum antifungal agent and is the backbone of the treatment for medically important opportunistic fungal pathogens in children. This study aimed to compare the nephrotoxicity associated with L-AmB in children with acute lymphoblastic leukemia and acute myeloid leukemia. MATERIALS AND METHODS: A total of 112 pediatric acute lymphoblastic leukemia or acute myeloid leukemia patients who received treatment with L-AmB (Ambisome®) at the University of Health Sciences Dr Behcet Uz Children's Hospital over 7 years were included. The incidence of hypokalemia, decreased estimated glomerular filtration rate and presence of acute kidney injury was recorded. RESULTS: The average L-AmB treatment duration was 17.1±15.0 days. Five patients (4.4%) of the patients had grade I acute renal injury according to KDIGO criteria and 16 patients (14.2%) had increased risk for kidney injury according to RIFLE criteria. There were no patients with eGFR decrease above 50% and no renal injury and failure were observed during L-AmB treatment. The rate of patients with hypokalemia in the pre-treatment was 17.9% and the post-L-AmB group was 50.0%. The rate of hypokalemia was higher in the post-treatment group (P=0.0015). Among the 112 patients, only two patients (1.7%) required cessation of L-AmB treatment due to resistant hypokalemia despite supplementation. CONCLUSIONS: Hypokalemia was more common compared to glomerulotoxicity and acute renal injury (according to KDIGO and RIFLE criteria) in pediatric leukemia patients treated with L-AmB. Hypokalemia developed in nearly half of the patients and the study shows the need for randomized controlled trials and strategies for hypokalemia associated with L-AmB treatment.

Effect of pyridoxine plus pyridostigmine treatment on vincristine-induced peripheral neuropathy in pediatric patients with acute lymphoblastic leukemia: a single-center experience.

BACKGROUND: Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity. AIMS: The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia. METHODS: The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013-February 2016 were prospectively evaluated. RESULTS: The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m2. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy. CONCLUSION: The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.

Children with chronic-refractory autoimmune cytopenias: a single center experience.

BACKGROUND AND OBJECTIVES: Autoimmune cytopenias are a group of heterogeneous disorders characterized by immune-mediated destruction of one or more hematopoietic lineage cells. The differential diagnosis of children with autoimmune cytopenias requires much time and laboratory investigations. The aim of the present study was to evaluate the clinical course and significance of autoimmune cytopenias due to immunodeficiency or autoimmune diseases in children at a single children`s hospital. METHOD: Between February 1997 and September 2015, chronic/refractory autoimmune cytopenias patient data were evaluated retrospectively. Twenty-three patients were assessed in this study. RESULTS: The median duration of following was 2.6 years (4 months-18.5 years). The median age of diagnosis was 3.1 years (6 months-16 years). A total of 13 patients (56.5%) had single-lineage and 10 (46.5%) had multilineage cytopenias. The most frequent single-lineage cytopenia was thrombocytopenia, followed by anemia. In 22 of the patients, cytopenias was detected before the primary diseases. All of the patients were treated with corticosteroids or intravenous immune globulin as first-line treatment. Ten patients (43.5%) needed second or further-line immunosuppressive therapies that patients diagnosed as systemic lupus erythematosus, hypogammaglobulinemia, or common variable immunodeficiency. A total of 8 patients (34.7%) recovered from autoimmune cytopenias after the treatment of primer disease. Cytopenias were continued in 14 patients. CONCLUSION: Cytopenia may be the first finding of an immunodeficiency or autoimmune disease and primary disease may be diagnosed in the clinical course. Taking the new targeted treatment options into consideration; early diagnosis is likely to become more important in the near-future in order to begin the treatment for the underlying disease as early as possible.

Successful Management of l-Asparaginase-Associated Pancreatitis With Octreotide and Pegylated Asparaginase in 2 Patients With Acute Lymphoblastic Leukemia: Is There a Different Rare Warning Sign of Hypoglycemia for l-Asparaginase-Associated Pancreatitis?

l-Asparaginase (l-Asp) is a critical component of chemotherapy for acute lymphoblastic leukemia (ALL). However, toxic effects associated with l-Asp, such as hepatic dysfunction, pancreatitis, hypercholesterolemia, and hyperglycemia, have occurred. In addition, acute pancreatitis is a significant life-threatening adverse event associated with ALL. We describe 2 patients with ALL who had l-Asp-associated pancreatitis (AAP), with one patient presenting with hyperglycemia and the other presenting with hypoglycemia during induction treatment. When octreotide was administered to both of these patients, the clinical findings and laboratory data were improved. AAP was not repeated after treatment with pegylated asparaginase. Although AAP has a high risk of mortality and morbidity in childhood, APP treatment with appropriate agents, such as octreotide, can be successful.

Idiopathic Pulmonary Hemosiderosis Mimicking Iron Deficiency Anemia: A Delayed Diagnosis?

Idiopathic pulmonary hemosiderosis (IPH) is an uncommon chronic disorder in children. It is characterized by recurrent pulmonary hemorrhage and may result in hemoptysis and pulmonary insufficiency. The most common hematologic manifestation of IPH is iron deficiency anemia. The etiology of IPH is not known and its diagnosis may be difficult due to the variable clinical courses. The most helpful signs for identifying IPH are iron deficiency anemia and recurrent or chronic cough, hemoptysis, dyspnea, wheezing. We report here 5 pediatric cases of IPH presenting with iron deficiency anemia and without pulmonary symptoms. Mean corpuscular volume was low in all patients; iron was low in 4 out of 5 cases; total iron binding capacity was high in all of them; ferritin was low in 3 patients. At follow up, none of them had responded successfully to the iron therapy. Although they didn't present with pulmonary symptoms, chest radiographs incidentally revealed diffuse reticulonoduler shadows in all of them. Computed tomography revealed diffuse ground-glass opacities, consolidation, increased density. The diagnosis was confirmed by the detection of hemosiderin-laden macrophages in bronchoalveolar lavage fluid and gastric aspirate. If patients with iron deficiency anemia don't respond to iron therapy, they should be examined for IPH. Chest radiographs should be taken even in absence of pulmonary symptoms. Early diagnosis is important for a timely management of IPH.

Assessment of sleep in pediatric cancer patients.

Ince D, Demirag B, Karapinar TH, Oymak Y, Ay Y, Kaygusuz A, Töret E, Vergin C. Assessment of sleep in pediatric cancer patients. Turk J Pediatr 2017; 59: 379-386. The purpose of the study is to describe sleep habits, assess the prevalence of sleep disturbances in pediatric cancer patients and healthy controls, and to compare sleep patterns, sleep problems. One hundred-thirty-five patients and 190 healthy controls were evaluated. Healthy children matched for age, sex, economic status, parental education and family structure constituted the control group. Sleep was evaluated by using the Children`s Sleep Habits Questionnaire (CSHQ). Sleep problems were detected in half of patients. There were no significant differences in total sleep score and subscale scores between patients and controls. Solely the wake-time was found significantly different between patients and controls. Although our results indicated that neither childhood cancer survivors nor patients with cancer during treatment period had more sleep problems than their healthy peers, sleep problems were not uncommon in whole study group. This study underlines the need to screen, assess and manage sleep problems in children with diagnosis of cancer.

Varicella-Zoster Virus Infections in Pediatric Malignancy Patients: A Seven-Year Analysis.

Primary varicella-zoster virus (VZV) infection is a benign self-limited disease. In this study, we review our experience in focusing on the outcome and treatment of VZV infection in pediatric malignancy patients. During the study period, a total of 41 patients with pediatric malignancy had been hospitalized with the diagnosis of VZV infection. All the patients were treated with intravenous acyclovir for a median of 7 days (ranging from 5 to 21 days). The calculated attributable delay of chemotherapy due to VZV infections was 8 days (ranging from 2 to 60 days). VZV-related complications were observed in 3 of 41 patients (7%) who suffered from acute respiratory distress syndrome, and one of them with hemophagocytic lymphohistiocytosis died due to respiratory failure despite acyclovir and broad-spectrum antimicrobial treatment plus supportive treatment. VZV infections are still important contagious diseases in pediatric cancer patients, because they cause not only significant mortality but also a delay in chemotherapy.

Granulocyte transfusion experience in pediatric neutropenic fever: Splitted product can be an alternative?

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

Management of Two Juvenile Myelomonocytic Leukemia Patients According to Clinical and Genetic Features.

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder of childhood. Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in approximately 80% of JMML patients. Distinct clinical features have been reported to be associated with specific gene mutations. The advent of genomic studies and recent identification of novel genetic mutations in JMML are important not only in diagnosis but also in the management and prognosis of the disease. Herein, we present 2 patients with JMML harboring different mutations, NRAS and c-CBL, respectively, with distinct clinical features and different therapeutic approaches.

Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy.

OBJECTIVE: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL). MATERIALS AND METHODS: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period. RESULTS: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI. CONCLUSION: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI.

CANDLE syndrome: a recently described autoinflammatory syndrome.

CANDLE syndrome (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) is a recently described autoinflammatory syndrome characterized by early onset, recurrent fever, skin lesions, and multisystemic inflammatory manifestations. Most of the patients have been shown to have mutation in PSMB8 gene. Herein, we report a 2-year-old patient with young onset recurrent fever, atypical facies, widespread skin lesions, generalized lymphadenopathy, hepatosplenomegaly, joint contractures, hypertrglyceridemia, lipodystrophy, and autoimmune hemolytic anemia. Clinical features together with the skin biopsy findings were consistent with the CANDLE syndrome. The pathogenesis and treatment of this syndrome have not been fully understood. Increased awareness of this recently described syndrome may lead to recognition of new cases and better understanding of its pathogenesis which in turn may help for development of an effective treatment.

The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol.

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20 × 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.

A rare complication of intrathecal methotrexate in a child with acute lymphoblastic leukemia.

Methotrexate (MTX) is an essential component of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Both intravenous and most commonly intrathecal routes of MTX have been implicated in acute, subacute, and chronic neurotoxicity syndromes. Subacute MTX neurotoxicity occurs within days to weeks after the intravenous or intrathecal therapy and characterized by a distinct presentation with remarkable clinical resemblance to stroke, including hemiparesis, hemisensory deficits, aphasia, dysarthria, dysphagia, and diplopia. Herein the authors describe the clinical and typical neuroimaging features of a female patient with ALL who presented with subacute MTX neurotoxicity that rapidly progressed to a severe clinical condition in a few hours but eventually resolved completely with dexamethasone and folinic acid. Subacute MTX neurotoxicity is a transient neurological dysfunction that should be considered in patients presenting with stroke-like and various neurological symptoms 10 to 14 days after intrathecal therapy and diffusion-weighted magnetic resonance imaging should be undertaken for the correct diagnosis and exclusion of possible ischemic infarct. Discontinuation of subsequent intrathecal MTX therapies should be considered in severe cases and treatment with dexamethasone and folinic acid may help to resolve the symptoms.