Gulsun Tezcan

Renal function after hematopoietic stem cell transplantation in children

The aim of this study was to assess glomerular and tubular renal function after HSCT in children in a prospective trial.

Heart Rate Variability in Patients with Thalassemia Major

Cardiac dysfunction, including congestive heart failure and fatal arrhythmia, is a frequent cause of death among children with thalassemia major (TM). Autonomic nervous system activity typically is measured by a series of cardiovascular autonomic function tests, but these tests are unsuitable for young patients because they are invasive or complex. Heart rate variability assessment is a technique that measures the beat-to-beat variability in R-R intervals. This variability reflects changes in autonomic activity and their impact on cardiovascular function. This study examined 32 patients with TM to evaluate heart rate variability (HRV) in a preclinical phase of cardiac involvement. The study patients showed no evidence of heart failure or signs of peripheral or autonomic neuropathy. All HRV parameters were significantly reduced in the TM patient group compared with the control group. The results of this study can be interpreted as evidence of early cardiac autonomic neuropathy in young thalassemic patients. Therefore, all TM patients should be screened using HRV analysis for that complication.

EPISODES OF FEVER AND NEUTROPENIA IN CHILDREN WITH CANCER IN A TERTIARY CARE MEDICAL CENTER IN TURKEY

The aim of this study was to determine the clinical features and microbiological spectrum during episodes of fever and neutropenia (FEN) in children with cancer. Demographics, clinical information, treatment approaches, and outcomes of the patients admitted to Akdeniz University Department of Pediatric Hematology and Oncology from October 1996 to June 2004 were evaluated retrospectively. Of the total 621 episodes, 345 (55.5%) were microbiologically documented (MDI) (36.4%) or clinically suspected (CSI) (19.2%) infections. A total of 425 infections were diagnosed in 345 episodes, in which lower respiratory tract infections were the most common (32.7%). Among the microbiologically documented infections, Staphylococci (both coagulase-negative and coagulase-positive) (38.7%) and Escherichia coli (12.9%) were the most frequently isolated gram-positive and gram-negative organisms, respectively. Monocytopenia less than 100/μL (p = 0.01), duration of neutropenia (p =. 01) and fever (p <. 001) were significantly associated with documented infection by univariate analysis. In addition, presence of previous FEN episode (p =. 001) and hypotension (p =. 029) were also found to be risk factors. However, using the multivariate analyses, only the duration of fever was found to be an independent risk factor for MDI. The rate of mortality was significantly higher among under 1-year-old patients (p =. 039). Hypotension and uncontrolled cancer were the significant determinants of poor prognosis. These results may help to consider a more selective management strategy for children with these problems.

Can serum cystatin C reflect the glomerular filtration rate accurately in pediatric patients under chemotherapeutic treatment? A comparative study with Tc-99m DTPA two-plasma sample method.

ObjectiveIt was assessed whether cystatin C (cysC) could be used as a marker of glomerular filtration rate (GFR) by considering the technetium-99m diethylenetriamine penta-acetate (Tc-99m DTPA)-two blood sample method (GFRTc-99m DTPA) as the reference in pediatric patients under chemotherapeutic treatment. MethodsThe chemotherapy group (CG) consisted of 31 patients (21 females, 10 males median age: 8.2 years; range: 2–16 years) who had been planned to receive allogenic hematopoietic stem cell transplantation. All patients in the CG received conditioning regimen (includes chemotherapy protocol) before hematopoietic stem cell transplantation. In addition, 21 patients (14 females, seven males median age: 9.5 years; range: 4–16 years) without any chemotherapy (nonchemotherapy group: nCG) were also prospectively investigated. Serum cysC, serum creatinine, GFRTc-99m DTPA, and GFR with a cysC-based formula (GFRcysC) were analyzed. Tubular function was also assessed. ResultsAlthough we found good correlation between GFRTc-99m DTPA and cysC (r = −0.78), GFRTc-99m DTPA and GFRcysC (r = 0.91), cysC and creatinine (r = 0.91) in nCG, the same correlations were poor in CG (r = −0.42, r = 0.43, r = 0.46, respectively). Tubular function was impaired after chemotherapy. Bias±1.96 SD values were −6±15.7 and −3±54.8 ml/min/1.73 m2 in nCG and CG, respectively. Precision was also better in nCG (10 ml/min/1.73 m2) than in CG (27.6 ml/min/1.73 m2). ConclusionSerum cysC and GFRcysC cannot reflect GFR accurately in pediatric patients under chemotherapeutic treatment. Tubular cell damage induced by chemotherapeutics could be a responsible factor through the impairment of tubular absorption and metabolism of cysC.

Unrelated cord blood transplantation in children with severe congenital neutropenia.

Abstract:  SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG‐CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG‐CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA‐matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+  cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post‐transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.

Analysis of human herpes virus 6 infections with a quantitative, standardized, commercial kit in pediatric stem cell transplant recipients after transplantation

BACKGROUND AND OBJECTIVES The aim of the study was to assess the incidence and clinical relevance of active Human Herpes Virus 6 (HHV6) infections in pediatric patients after allogeneic stem cell transplantation. DESIGN AND SETTINGS Retrospective analysis of samples prospectively collected at Akdeniz University Medical Faculty Hospital, Antalya, Turkey, between May 2006 and July 2007 from 15 pediatric patients with allogeneic hematopoietic stem cell transplantation (HSCT). SUBJECTS AND METHODS A commercial quantitative real-time polymerase chain reaction kit was used to analyze plasma samples collected from 15 pediatric allogeneic HSCT recipients. RESULTS HHV6 DNA was found positive in 8 (53%) patients. HHV6 DNA levels above 1000 copies/mL were found only in 2 patients and they were also consecutively positive for HHV6 DNA. Age at transplantation, use of ATG, and receiving grafts other than HLA identical siblings increased the risk, with a statistically significant difference, of having HHV6 reactivation with levels exceeding 1000 copies/mL (P values, respectively, P=.03, .001, .025). Active HHV6 infections with HHV6 viremia levels higher than 1000 copies/mL were associated with subsequent delayed platelet engraftment (P=.001), acute graft versus host disease (P=.001), skin rash, and fever of unknown origin. CONCLUSION More than half of pediatric allogeneic HSCT patients develop active HHV6 infection, and especially in patients with high viremic loads, the infection can result in serious clinical situations. A clinically significant cutoff value for viremia seems to be necessary to predict serious clinical complications.

Aberrations of Chromosomes 9 and 22 in Acute Lymphoblastic Leukemia Cases Detected by ES-Fluorescence In Situ Hybridization

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.

Embryonic rhabdomyosarcoma presenting as endobronchial tumor in an adolescent

To the Editor: Primary pulmonary or endobronchial tumors are not common in childhood [1]. As a result, individual experience with the diagnosis, management, and prognosis is limited. Our experiencewith this problem is of interest. Twelve-year-old male patient with the complaint of cough and hemoptysis of 3 months duration was hospitalized because of respiratory distress requiring mechanical ventilation in a state hospital. Chest X-ray demonstrated loss of volume. Computed tomography (CT) scan was performed and it was valuable in defining a polypoid mass in the proximal part of the left primary bronchi near to the tracheal bifurcation, 4 4 mm in diameter (Fig. 1) and was also helpful in defining subcarinal lymph node near to the posterior-medialwall of the right primary bronchi (Fig. 2). Bronchoscopy showed a polypoid mass near to tracheal bifurcation and biopsy of the mass revealed it to be an embryonel rhabdomyosarcoma. He was referred us for further care. On physical examination, auscultation revealed barely audible breath sounds and it was the only pathological finding. Bronchoscopy was repeated in our center and endobronchial polypoid mass near to tracheal bifurcation was seen. Evaluations of other organ systems did not show any evidence of disease. Laboratory investigations were also in normal limits. Pathological diagnosis was confirmed by the pathologist in our center. He was accepted as Group III-A according to the Intergroup Rhabdomyosarcoma Study Group (IRS) Clinical Grouping System, Stage III (T1-a-N1) according to TNM system. Chemotherapy for soft tissue sarcomas consisting of ifosfamide, cisplatin, adriamycin, and vincristine was started. After the first course, evaluation by CT scan showed the disappearance of endobronchialmass; however subcarinal lymph nodewas the same in size. After the second course, the lymph node also diminished in size. Since at the beginning complete surgical removal could not been accomplished, following six cycles of chemotherapy radiotherapy was administered. Primary tumor site received hyperfractionated radiation of 5,940 cGy. He is still alive and free of disease for 4 years. Although primary endobronchial or pulmonary tumors are very infrequent in childhood, early investigation and surgical intervention are essential in children with persistent pulmonary symptoms or X-ray abnormalities even though presenting symptoms and signs are not specific in nature. Though endoscopic resection of endobronchial lesions is possible in many cases, local invasion and the risk of hemorrhage make this modality less than optimal [2]. Rhabdomyosarcoma can affect the lung but only accounts for 0.5% of childhood