Ayşe Erbay

THE EVALUATION OF BLOOD DONOR DEFERRAL CAUSES

Safety of blood and blood products is a major problem all over the world. Screening for the markers of infectious diseases is an incomplete solution. One of the most important steps in improving the safety of blood and blood products is donor selection. In this study, causes of donor deferral were evaluated retrospectively in the blood center of a childrens hospital. Analysis of the deferrals showed that the most commonly defined causes were recent sexual exposure in high-risk activity, recent ingestion of medication, low hemoglobin level, abnormal blood pressure, being underweight, tattoos, piercing or acupuncture in the preceding 6 months, recent history of infection and presenting for a subsequent donation too soon, elevation of transaminases, presence of the markers of the infectious diseases.

Evaluation of telomerase mRNA (hTERT) in childhood acute leukemia

Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children.

High-dose oral methylprednisolone therapy in childhood hemangiomas.

The authors report their experience with high-dose oral methylprednisolone therapy (HDMP)in 15 infants with complicated hemangiomas. The starting dose for methylprednisolone was 30 mg/kg/day for 5 days, then the dose was tapered gradually every 5 days to 20, 10, 5, 2.5, and finally to 1 mg/kg/day. Therapy was then stopped and the patients were followed. An initial response was evident in 12 patients. Nine out of 12 responders showed regrowth signs. After regrowth, 4 cases received prednisolone at doses between 1 to 5 mg/kg/day and 3 patients received a second course with HDMP as additional corticosteroid therapy. Overall, 9 out of 15 cases were responders; very good and good responses were obtained in 5, partial response in 4, and therapy failure in 5 cases. One child was not available for evaluation of response. A very rapid initial response was observed in subglottic and periocular hemangiomas. Side effects were not serious and resolved after discontinuation of treatment. Although the number of patients is small in this study, overall response rate with HDMP regimen seems not to be superior to the regimens that use lower doses (5 mg/kg/day), but it provides a high initial response rate and the duration of therapy is short. Therefore, it may be useful for treating hemangiomas that fail to respond with low doses, especially in centers with limited resources where other treatment modalities cannot be used at the moment.

Prognostic Significance of Cell Proliferation and Apoptosis-Regulating Proteins in Epstein-Barr Virus Positive and Negative Pediatric Non-Hodgkin’s Lymphoma

Apoptosis-related proteins and proliferation activity and their relationship with Epstein-Barr Virus (EBV) are contemporary issues in pediatric non-Hodgkin’s lymphoma (pNHL). In this study prognostic or pathogenetic role of EBV latent infection, proliferating activity, and apoptosis-regulating proteins in pNHL were explored. EBV-EBER, lmp-1, ki-67, bcl-2, survivin, bax, fas, c-myc, p53 and apoptotic index by TUNEL method were explored in 70 pNHL cases and evaluated statistically. Of the 70 cases evaluated, 24 were female and 46 were male. Seven cases were stage I/II and 63 cases were stage III/IV. The mean age was 7.16 ± 3.72(1–15). EBV was positive in (25.7%) cases. Overall survival was 82%, while event free survival was 75%. Bax was expressed in 40% of the cases, while the expression of bcl-2,was 50%, survivin 42.9%, p53 8.6%, fas 18.6% and c-myc in 45.7%. Mean apoptotic index was 131.29 ± 96.69 per 5,000 cells. Mean proliferation index was 55.97% (12–92%). Fas positivity was high in EBV positive cases (p = 0.0001). EBV positivity was not related with prognosis. Apoptotic index was found to be an independent prognostic factor (p = 0.017). Our results suggest that apoptosis-regulating proteins have a role in the pathogenesis of pNHL. EBV was correlated with apoptotic index and fas, bcl-2. No correlation was observed with proliferation index and studied factors. High apoptotic index was related with good prognosis.

Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: A report of two cases.

We report two male cases (4- and 5-years-old) of intrathecal methotrexate overdose. The two boys with acute lymphoblastic leukemia were to receive intrathecal injection of methotrexate. Instead of the prescribed 12 mg, they both received a dose of 120 mg. The initial cerebrospinal fluid samples showed methotrexate concentration of 2.24x10-2M in case 1 and 1.32x10-2M in case 2. The cases were successfully treated with cerebrospinal fluid (CSF) exchange and intravenous folinic acid rescue. The favorable outcome in our cases suggests that CSF exchange is safe and that folinic acid rescue may be adequate to prevent sequelae in patients subjected to intrathecal MTX overdoses up to 120 mg. We propose CSF exchange and intravenous folinic acid as the mainstay of treatment. In addition to the staffs failure to check the drug label carefully, the marked resemblance of the two dose preparations of MTX may have been contributory.

Secondary Hemophagocytic Lymphohistiocytosis: Do We Really Need Chemotherapeutics for All Patients?

Because of the acute and life-threatening course of the hemophagocytic lymphohistiocytosis (HLH) syndrome, International Histiocyte Society guidelines recommend chemoimmune therapy for the treatment of both primary and secondary HLH (sHLH). To manage children with sHLH, instead of HLH-2004 protocol we considered less immunosuppressive/cytotoxic approach. We assessed 12 children who fulfilled the diagnostic criteria for sHLH between January 2009 and March 2015. Multivariate Cox regression analysis showed that ferritin levels (hazard ratio=1.02, P=0.006), pediatric logistic organ dysfunction scores (hazard ratio=1.01, P=0.001) were the predictors of the survival. The hospital survival was 83% for patients with sHLH who were treated with less immunosuppressive therapy. In conclusion initiation of HLH-specific therapy for the patients with hyperferritinemia-associated sHLH should be delayed while awaiting resolution of systemic inflammation with less immunosuppressive therapy.

PULMONARY HYPERTENSION IN A CHILD WITH JUVENILE MYELOMONOCYTIC LEUKEMIA SECONDARY TO PULMONARY LEUKEMIC CELL INFILTRATION

A 4-year-old girl with juvenile myelomonocytic leukemia presented to the emergency room with dyspnea. Echocardiography was performed due to cardiomegaly and prominent main pulmonary artery on a chest X-ray film. On echocardiography the right ventricular pressure calculated from the velocity of tricuspid regurgitation jet was 55 mmHg with no pulmonary stenosis. Despite treatment for pulmonary hypertension and provision of respiratory support, the patient died. A postmortem lung biopsy specimen showed infiltration by tumor cells, which suggested that the pulmonary hypertension had been caused by leukemic infiltration. In conclusion, the findings suggest that leukemic infiltration into the lungs may occur in children with juvenile myelomonocytic leukemia. It should be recognized as a potentially treatable cause of pulmonary hypertension in patients with juvenile myelomonocytic leukemia.

Prognostic significance of cyclooxygenase-2 expression in pediatric Hodgkin and non-Hodgkin lymphomas with or without Epstein–Barr virus latent infection

The aim of this study is to investigate the expression of cyclooxygenase-2 (COX-2) and the relationship between COX-2, prognosis and Epstein–Barr virus (EBV) in pediatric Hodgkin (pHL) and non-Hodgkin lymphomas (pNHL). Cyclooxygenase-2 is frequently overexpressed in various tumors. COX-2 inhibitors’ potential use as a therapeutic target in onco-hematology and its relation with EBV is a contemporary question. A potential role for COX-2 in EBV-associated human cancers was suggested. The role of COX-2 in EBV-related oncogenesis of pHL and pNHL is not studied. The expression of COX-2, latent membrane protein 1 and Epstein–Barr virus-encoded early RNA was detected by immunohistochemistry and in situ hybridization in 63 pHL and 70 pNHL. The results were scored as positive or negative. The statistical significance was assessed by correlation, survival analysis, and nonparametric tests. In pNHL cases, the mean age was 7.16 ± 3.72. EBV was positive in 18 cases, COX-2 in 16 cases (22.8%). Expression of COX-2 did not correlate with age, sex, stage, phenotype, histology, EBV positivity, and response rate to therapy. In pHL cases, the mean age was 8.46 ± 3.54. EBV was positive in 52(82.5%), COX-2 in 36(57.1%) cases. The expression of COX-2 protein did not correlate with age, sex, stage of disease, EBV positivity, and response to therapy. COX-2 expression was higher in nodular sclerosing and lymphocyte-rich histology. In log rank analysis, no statistical significance for prognosis was observed. In this series, COX-2 was found to be expressed in the minority of pNHL tissues and more than half in pHL cases especially in NS type. This might be related with fibrosis of NS cases. It did not correlate with prognosis. COX-2 expression did not seem to have a synergistic role with EBV in the pathogenesis of pediatric lymphomas. It will be useful studying the relationship of COX-2 expression with apoptotic and other factors in pediatric lymphomas.