Plasma Levels of Plasminogen Activator Inhibitor Type 1 and Vitronectin in Children With Cancer.

BACKGROUND: The plasminogen activator system controls intravascular fibrin deposition; besides, it also participates in a wide variety of physiologic and pathologic processes, including cancer. PROCEDURE: In this study, we examined the levels of plasminogen activator inhibitor 1 (PAI-1) and vitronectin in 32 newly diagnosed pediatric patients with malignancies, determined by enzyme-linked immunosorbent assay between January 2009 and January 2010 and compared them to 35 age-matched healthy children, using SPSS 16.0 software. RESULTS: The mean level of PAI-1 was 23.02 ± 15 (8.2-71.19) ng/mL and vitronectin was 83.10% ± 23.77% (12%-126%) in the tumor group. Thirty-five healthy children in the same age range were enrolled in the control group. The levels of PAI-1 and vitronectin were 23.63 ± 10.44 (11.67-58.85) ng/mL and 85% ± 20.85% (39%-126%), respectively. No significant difference was found between the 2 groups by independent sample t-test (P = .86 and P = .69). CONCLUSIONS: This is a preliminary study done in children with malignancies, investigating PAI-1 and vitronectin. Further study is needed, including larger trials and tumor tissue with histopathological examination as in adults.

Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

Cerebrospinal fluid dynamics of the cava septi pellucidi and vergae. Case report.

This case involved a 26-month-old boy who had recurrent hemorrhagic venous infarction caused by venous sinus occlusion. Distension and enlargement of the cavum septi pellucidi (CSP) and cavum vergae (CV), along with hydrocephalus, was detected during the course of the disease and was observed to regress together with resolution of the venous occlusion. Venous hypertension caused by sinus occlusion was thought to be responsible for the disturbed resorption of cerebrospinal fluid (CSF) in the CSP and CV in this patient. This case is unique because it is the first one to support the hypothesis of resorption of CSF in the cava by a pressure gradient involving the septal capillaries and veins.

The efficacy of mezlocillin-amikacin combination in febrile neutropenic children with oncologic disease.

The efficacy of mexlocillin-amikacin combination as empirical therapy for febrile neutropenic patients was studied in 30 children (21 males, 9 females) with various oncologic diseases aged 1-15 years (mean age 7.3 +/- 4.4) in the Istanbul Medical School, Oncologic Disease Research and Treatment Center, and Department of Pediatric Hematology-Oncology between January 1 and May 31, 1988. The response rate was 76.6%. Profound persistent granulocytopenia (fewer than 100 ml) was present in 70% of the patients. In 63.3% of patients, the infections were microbiologically documented (60%) Gram(+) and 40% Gram(-). The combination was well tolerated with hepatic and/or renal disturbances in 8 cases (26.6%). We conclude that mezlocillin-amikacin is an effective empirical combination in the initial treatment of infections in febrile neutropenic children with various oncologic diseases.

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Results of rhabdomyosarcoma treatment in a developing country.

Fifty-one children (median age: 4.5 years; 4 months-16 years) diagnosed with rhabdomyosarcoma were treated in our center between 1980-1999. The primary sites were head and neck in 31.4%, the genito-urinary system in 21.6%, and extremities in 9.8% of the patients. The histopathologic subtypes were embryonal in 80.4%, alveolar in 9.8%, and undifferentiated in 9.8%. The majority of the patients were considered group III (47%) and group IV (25.5%) according the criteria of the Intergroup Rhabdomyosarcoma Study (IRS). Primary total tumour resection was performed in only 27.5% of the patients. The patients were treated with assigned regimens of IRS II and IRS III protocols. Radiotherapy was applied to 92.1% of the patients. Thirty-four patients (66.7%) were lost to follow up, and of the remaining 17 patients, 7 patients (41.2%) died, relapse occurred in 9 patients (52.9%) and 10 patients (58.8%) are alive. The percentage of cases lost to follow up during the first 10 years and the following 9 years of the study were 77.4% and 50%, respectively. In compliance with cancer treatment remains a major problem in developing countries.

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of relapsed or poor risk childhood acute leukemia.

The prognosis of relapsed acute leukemia or chronic leukemia in acute blast crisis is poor and new chemotherapeutic regimens could be useful for these patients. Six relapsed acute lymphoblastic leukemia (ALL), nine relapsed acute myeloblastic leukemia (AML), one chronic myelomonocytic leukemia (CMML) and one chronic myeloid leukemia (CML) in acute blast crisis between three to 18 years (median 10 years) received fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) chemotherapy (CT). Five of the AML relapses were after bone marrow transplantation (BMT) and four were recurrent relapses. At the end of the second course only three patients (2 AML, 1 ALL) were in complete remission (CR). Of the three patients in CR, one patient with AML had her first donor lymphocyte transfusion (DLT) on the 7th day of the second FLAG-IDA course and she is disease-free on the 30th month of the second remission. The remaining two patients were transplanted from unrelated donors in a BMT center abroad on the 5th and 8th month of the last remission and both died with BMT-related complications. Out of 25 courses, seven resulted in fatal infections. The regimen was ineffective in B-cell ALL as in acute blastic crisis of CMML and CML. We could not evaluate the remission-inducing effect accurately in most of the patients due to induction failure. FLAG-IDA appears to be a myelotoxic therapy for relapsed or poor risk leukemia in a developing country. It is not cost-effective; dose modifications or a regimen without IDA may be tried if there is an available marrow donor.

Cardiac extension of Wilms' tumor.

Two children who were brought to the Istanbul Children's Hospital with congestive heart failure caused by extension of Wilms' tumor to the right atrium are presented. In both cases a large mass was noted in the right atrium by two-dimensional echocardiography. The tumors were successfully removed at open heart surgery, and chemotherapy and radiotherapy were started postoperatively. The patients are both alive and symptom-free; one, three and a half years and the other two years postoperatively.

Acute lymphoblastic leukemia: dental health of children in maintenance therapy.

The dental health of 41 children aged 4-16 years who were in maintenance therapy from acute lymphoblastic leukemia (ALL) was examined in relation to the period of time in maintenance. There was no significant difference in dental experience and salivary flow rate between the control group and patients with leukemia. Performed treatment index (PTI) and required treatment index (RTI) scores reflected that children, who were in maintenance therapy had insufficient dental care and needed more dental treatments. A statistically significant difference in salivary pH was found between the children, who were in maintenance therapy for 12-24 months and less than 12 months and also the control group; but the pH scores of all groups were observed in normal limits.

Prognostic significance of wilms tumor 1 gene in childhood acute Lymphoblastic Leukemia.

Wilms tumor 1 (WT1) gene is a tumor supressor gene, expressed in malignant and normal hematopoietic progenitor cells. Prognostic significance of this gene in childhood acute lymphoid leukemia (ALL) is not clear. We evaluated the presence of WT1 expression in bone marrow samples of 28 children with de novo ALL at diagnosis by two step RT-PCR. Expression of WT1 gene was detected in 78.5% of patients. There was no correlation between WT1 gene expression and age, sex, FAB type, leukocyte count, and presence of t(4;11) and t(9;22). All patients were treated with modified BFM 86 protocol. There was no difference in the complete remission (CR) rate between WT1 positive and negative patients. Event free survival (EFS) and overall survival (OS) of WT1 positive and negative patients were also not significant. We conclude that expression of WT1 gene is not associated with specific characteristics of ALL blast cells and is not a prognostic factor for CR, remission duration and overall survival.

Detection of BCR/ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute Lymphoblastic Leukemia: incidence and clinical eatures.

BCR/ABL expression, which is the molecular equivalent of the Philadelphia chromosome, is an independent poor risk factor in acute lymphoblastic leukemia (ALL). We used a two-step (nested) reverse transcriptase polimerase chain reaction (RT-PCR) assay to examine BCR/ABL expression in the diagnostic bone marrow specimen of children with ALL, prospectively. Among 75 de novo ALL patients, 4 (%5.3) were found to be BCR/ABL- ositive, whereas 4 of 17 relapsed patients (23.5%) were positive. This preliminary study in Turkish children showed an incidence similar to reports from Europe and the U.S.A. More intensive chemotherapies and allogeneic bone marrow transplantations (BMT) uring the first remission were planned if a donor was available. Out of 8 BCR/ABL-positive patients, complete remission (CR) was achieved in 7 patients and partial remission (PR) was achieved in 1 patient. Three patients underwent allogeneic BMT during the first CR and 1 under went autologous BMT during the first PR. The Kaplan-Meier estimate of vent-free survival (EFS) of BCR/ABL negative de novo ALL patients was 78.36% at 3 years, whereas the EFS of positive patients was 31.25% at 26 ± 6.4 months. Molecular screening for the Philadelphia chromosome should become a part of the routine diagnostic panel in ALL patients in order to predict which patients have a poor prognosis and need tailored therapy.

Secondary hemophagocytic lymphohistiocytosis induced by malaria infection in a child with Langerhans cell histiocytosis.

Since the first description of infection-associated hemophagocytosis (IAHS), the list of precipitating infectious agents causing hemophagocytic syndrome has grown. A lymphohistiocytic proliferation with hemophagocytosis may develop as a result of macrophage activation, viral or bacterial infection, parasitic infestations, or malignancy. The authors report on a 3-year-old boy with Langerhans cell histiocytosis (LCH), who developed IAHS during malaria infection. Hemophagocytic syndromes may complicate the course of LCH and cause diagnostics problems. Malaria is one of many infections that can precipitate secondary hemophagocytic lymphohistiocytosis.

Is AML1/ETO gene expression a good prognostic factor in pediatric acute myeloblastic leukemia?

To assess the clinical significance of AML1/ETO gene detected by nested reverse transcriptase polymerase chain reaction, the outcome of 7 patients with acute myeloblastic leukemia between 3 and 14 years of age were presented. All patients had complete remission (CR) at the end of induction (AML-MRC 10 protocol) and 4 underwent unpurged autologous, 2 allogeneic (from matched siblings) non-T-cell-depleted bone marrow transplantations (BMT) in first CR. One patient died due to allogeneic BMT-related complications, and 4 patients relapsed at 13, 17, 18, and 26 months. Only one patient achieved second CR. All relapsed patients died between 18 and 36 months with resistant disease (n = 3) or infection during salvage chemotherapy (n = 1). Two patients who had autologous BMT are alive and disease free at 44 and 50 months. Although statistical significance could not be shown, event-free survival and overall survival rates of AML1/ETO-positive patients (28.57 and 28.57%, respectively) at 3.5 years were even lower than those of AML1/ETO-negative patients. The results confirm some previous reports that AML1/ETO gene in children and adolescents is not a favorable prognostic factor.