Birol Baytan

Assessment of bone mineral density and risk factors in children completing treatment for acute lymphoblastic leukemia.

Background Reduced bone mineral density and increased fracture risk have been reported in children with cancer. In this study, we aimed to determine the growth and bone mineral density (BMD) of the children off chemotherapy for acute lymphoblastic leukemia, and the probable risk factors. Procedure The age, anthropometric measurements, lumbar spine BMDs were recorded in 70 children. The risk factors on BMD; daily calcium intake, the time interval from the completion of the chemotherapy, cranial radiotherapy, cumulative steroid dose, decrease in physical activity were investigated. Serum calcium, phosphate, alkaline phosphates, magnesium, insulin-like growth factor-1 (IGF-1) and 25 (OH) vitamin D levels were determined. Results The mean height percentile at the time of diagnosis was decreased from the value of 53 to a value of 47 at the beginning of the study (P=0.071). Of them; 44% had osteoporosis, 41% had osteopenia, and the rest had normal BMD. BMD z-scores were decreased during the first 2 years from the completion of the treatment. There was a positive correlation between BMD z-scores and daily calcium intake (CC=0.366, P=0.0015). A negative correlation was determined between the time spent on TV and computers and BMD z-scores (CC=−0.464, P=0.0019). Serum IGF-1 and 25 (OH) vitamin D levels of patients were significantly lower than controls (P=0.033). Conclusions Our data revealed that 85% of the survivors had bone mineralization defect. BMDs and z scores were decreased during the first 2 years from the completion of the treatment and then gradually began to increase. The most important risk factor for decreased BMD was low daily calcium intake. Therefore, patients and their families should be encouraged to take sufficient amount of calcium. Prophylactic vitamin D may also be supplemented.

Risk factors for intraventricular haemorrhage in very low birth weight infants.

Objective: In a prospective study at Uludag University Hospital, 120 premature infants with birthweights of 1500 g or less were screened for intraventricular hemorrhage (IVH) using cranial ultrasound. With the purpose of studying the incidence of IVH, the associated risk factors for these neonates were considered.Methods : We studied all the very low birth weight infants admitted in our neonatal unit. We examined the following variables as risk factors for IVH: sex, birth weight, gestational age, Apgar score, mechanichal ventilation, hypercapnia, use of antenatal steroids, tocolytic drugs, vaginalversus cesarean section delivery, and inbornversus outborn status, vasopressor infusion (any vasoactive drug such as dopamine, dobutamine, or epinephrine) not associated with resuscitation, and surfactant administration.Results :The incidence of IVH was 15% (18/120), 50% grade I (9/18), 17% grade II (3/18), 11 % grade III (2/18), and 22% grade IV (4/18). IVH occurred mainly in the first week of life (78%; 14/18). The significant risk factors for IVH were found to be prematurity, outborn status, low 5 minute Apgar score, vaginal delivery, hypercapnia, mechanical ventilation, hypotension, and use of vasopressors on the day of admission. Significant protective factors against IVH included antenatal steroid therapy, cesarean section, magnesium sulfate tocolysis, increasing gestational age, and increasing birth weight.Conclusion: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Transportation of infantsin utero to a perinatal center specializing in high risk-deliveries results in a decreased incidence of IVH when compared to infants transported postnatally. Aggressive resuscitation, with avoidance of hypercarbia, and rapid restoration of hypovolemia could potentially reduce the incidence of PVH/IVH

Involuntary movements during vitamin B12 treatment.

It has been known for many years that vitamin B12 deficiency can cause neurologic problems. One of these problems is involuntary movements that can appear both before and after the initiation of vitamin B12 treatment. Here, we report 3 infants who developed movement disorder during vitamin B12 administration. The movement disorder consisted of a combination of tremor and myoclonus affecting face, tongue, and limbs. Because of the severity of the symptoms, they all needed symptomatic treatment. In 2 of them, the involuntary movements resolved with clonazepam. The involuntary movements in the other patient were successfully treated with piracetam.

Catheter-associated bloodstream infections in pediatric hematology-oncology patients.

Catheter-associated bloodstream infections (CABSIs) are common complications encountered with cancer treatment. The aims of this study were to analyze the factors associated with recurrent infection and catheter removal in pediatric hematology-oncology patients. All cases of CABSIs in patients attending the Department of Pediatric Hematology-Oncology between January 2008 and December 2010 were reviewed. A total of 44 episodes of CABSIs, including multiple episodes involving the same catheter, were identified in 31 children with cancer. The overall CABSIs rate was 7.4 infections per 1000 central venous catheter (CVC) days. The most frequent organism isolated was coagulase-negative Staphylococcus (CONS). The CVC was removed in nine (20.4%) episodes. We found that hypotension, persistent bacteremia, Candida infection, exit-side infection, neutropenia, and prolonged duration of neutropenia were the factors for catheter removal. There were 23 (52.2%) episodes of recurrence or reinfection. Mortality rate was found to be 9.6% in children with CABSIs. In this study, we found that CABSIs rate was 7.4 infections per 1000 catheter-days. CABSIs rates in our hematology-oncology patients are comparable to prior reports. Because CONS is the most common isolated microorganism in CABSIs, vancomycin can be considered part of the initial empirical regimen.

Reversible Posterior Leukoencephalopathy Induced by Cancer Chemotherapy

Reversible posterior leukoencephalopathy, defined by both clinical and neuroimaging findings, can affect children receiving chemotherapy. The syndrome is characterized by hypertension, alterations in mental status, seizures, hallucinations, and acute visual changes and is associated with abnormalities seen in magnetic resonance imaging of symmetric white matter lesions, especially in the parietal and occipital lobes. The etiology of reversible posterior leukoencephalopathy is as yet unknown. Presented here are four cases of reversible posterior leukoencephalopathy induced by chemotherapy, with a brief review of the literature and consideration of possible mechanisms. A diagnosis of reversible posterior leukoencephalopathy should be considered when patients receiving cancer chemotherapy suddenly develop hypertension followed by neurologic complications, especially if presenting with seizures.

The influence of risk factors in promoting thrombosis during childhood: the role of acquired factors.

Thrombo-embolism in childhood is a multifactorial disorder. The present study is a case-control study that investigated the role of genetic and acquired risk factors in 60 children with thrombosis and compared the results with the controls. Acquired and inherited risk factors precipitating thrombosis were present in 75 and 40% of the thrombotic children, respectively. The most frequent acquired risk factor was infection (58%). Of the genetic factors, factor V G20210A was the most common (38%). The comparison of the genetic and acquired risk factors in thrombotic versus nonthrombotic settings identified that acquired factors played a more significant role in causing thrombosis (OR:14.44; 95% CI: 7.05–29.94, p <. 001). This study has clearly suggested that the prevention of acquired risk factors, particularly infection, could decrease the risk of thrombosis in pediatric cases.

Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors

Summary.  The development of an inhibitor against factor VIII (FVIII) is a serious complication in children with haemophilia A. Immune tolerance induction (ITI) therapy is generally considered to be the best approach to eradicate the inhibitor. In this paper, the low‐dose (≤50 IU kg−1 twice or three times weekly with plasma‐derived factor concentrates) ITI regimen used in Turkey is discussed. This regimen was given to 21 haemophilia A patients with high titer inhibitors. The median age at the beginning of ITI was 9 years and exposure days were 25. The median pre‐ITI historical peak inhibitor titer, and inhibitor titer when ITI started were 80 BU (range 6.0–517), 19.2 BU (range 3.6–515), respectively. Complete immune tolerance was defined as the time at which at least two negative inhibitor assays was obtained with no anamnestic response. Our two cases were not reached in follow‐up period. Immune tolerance could be achieved in 5 of 19 (26.3%) patients within a median time of 6 months. Partial tolerance was obtained in 7 patients while treatment failed in spite of significant decreased inhibitor levels in the other patients. A relapse developed in one immune‐tolerized patient, one year later. The level of inhibitor titer at the beginning of ITI (≤10 BU), the pre‐ITI historical peak inhibitor titer (<50 BU), and the time between the first diagnosis inhibitor to starting ITI (<12 months) were main factors in the success (complete or partial tolerance) of ITI. In conclusion, the outcome of low‐dose ITI protocol was not satisfactory in this retrospective study.

Childhood Immune Thrombocytopenia: Long-term Follow-up Data Evaluated by the Criteria of the International Working Group on Immune Thrombocytopenic Purpura

Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood, characterized by isolated thrombocytopenia. The International Working Group (IWG) on ITP recently published a consensus report about the standardization of terminology, definitions, and outcome criteria in ITP to overcome the difficulties in these areas. Materials and Methods: The records of patients were retrospectively collected from January 2000 to December 2009 to evaluate the data of children with ITP by using the new definitions of the IWG. Results: The data of 201 children were included in the study. The median follow-up period was 22 months (range: 12-131 months). The median age and platelet count at presentation were 69 months (range: 7-208 months) and 19x109/L (range: 1x109/L to 93x109/L), respectively. We found 2 risk factors for chronic course of ITP: female sex (OR=2.55, CI=1.31-4.95) and age being more than 10 years (OR=3.0, CI=1.5-5.98). Life-threatening bleeding occurred in 5% (n=9) of the patients. Splenectomy was required in 7 (3%) cases. When we excluded 2 splenectomized cases, complete remission at 1 year was achieved in 70% (n=139/199). The disease was resolved in 9 more children between 12 and 90 months. Conclusion: Female sex and age above 10 years old significantly influenced chronicity. Therefore, long-term follow-up is necessary in these children.

AML1 amplification and 17q25 deletion in a case of childhood acute lymphoblastic leukemia

We report a case of childhood acute lymphoblastic leukemia (ALL) with both acute myeloid leukemia 1 (AML1) amplification and 17q25 deletion. AML1 gene is located on 21q22 and encodes a transcription factor. AML1 amplification is a common finding in childhood ALL, and itis observed as an increase in gene copy number by the FISH analysis. The mechanism of AML1 amplification is not associated with AML1 gene mutations. The 17q25 is a gene‐rich chromosomal location and distinct abnormalities of this region have been observed in previous cases of different kinds of leukemia. Deletion of the 17q25 region has been reported in two leukemia patients. Septin 9 (SEPT9) and survivin genes are located on 17q25. High expression of these genes and AML1 amplification are regarded as markers in tumorigenesis and disease progression; however, more data are needed for accurate prognostic evaluation. J. Clin. Lab. Anal. 23:368–371, 2009.

Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia

BACKGROUND The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. PATIENTS AND METHODS We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. RESULTS Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. CONCLUSIONS Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity.