The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.

No abstract

Abstract. The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T-or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T-cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.

This study analyzes the data of thrombotic children who were followed up in different pediatric referral centers of Turkey, to obtain more general data on the diagnosis, risk factors, management, and outcome of thrombosis in Turkish children. A simple two-page questionnaire was distributed among contact people from each center to standardize data collection. Thirteen pediatric referral centers responded to the invitation and the total number of cases was 271. All children were diagnosed with thromboembolic disease between January 1995 and October 2001. Median age at time of first thrombotic event was 7.0 years. Of the children 4% of the cases were neonates, 12% were infants less than 1 year old, and 17% were adolescents. Thromboembolic event was mostly located in the cerebral vascular system (32%), deep venous system of the limbs, femoral and iliac veins (24%), portal veins (10%), and intracardiac region (9%). Acquired risk factors were present in 86% of the children. Infection was the most common underlying risk factor. Inherited risk factors were present in 30% of the children. FVL was the most common inherited risk factor. Acquired and inherited risk factors were present simultaneously in 19% of the patients. Eleven children had a history of familial thrombosis. Due to the local treatment preferences, the treatment of the children varied greatly. Outcome of the 142 patients (52%) was reported: 88 (62%) patients had complete resolution, 47 (33%) had complications, 12 (9%) had recurrent thrombosis, and 34 (24%) died. Three children (2.1%) died as a direct consequence of their thromboembolic disease. The significant morbidity and mortality found in this study supports the need for multicentric prospective clinical trials to obtain more generalizable data on management and outcome of thrombosis in Turkish children.

The aim of our study was to show how the progression and severity of Familial Mediterranean Fever (FMF) is affected by procoagulant activity and alterations in the markers of thrombosis and fibrinolysis. The study cohort comprised 64 FMF patients who were classified as attack-free patients (Group 1; n = 34 patients, aged 3-19 years) and attack patients (Group 2; n = 30 patients, aged 3-21 years). All patients were on colchicine treatment with the exception the newly diagnosed patients in Group 2. A total of 14 healthy subjects between 5-12 years of age were enrolled as controls (Group 3). Laboratory tests, including leukocyte and thrombocyte counts, erythrocyte sedimentation rate, CRP, fibrinogen, PT, aPTT, Factor VIII, vW factor, D-dimer, P-selectin, tPA and PAI-1, were carried out on all patients. Inflammation continued both during the attack and attack-free period in FMF. The prolongation of PT was observed during attacks (PT = 13.6 s in Group 2, and PT = 12.6 s in Group 3; p = 0.002). tPA levels increased in FMF patients (tPA levels of group 1, 2 and 3 were 12.6, 13.2 and 9.7 ng/ml, respectively; p = 0.01). P-selectin was lower in both patient groups than in the control group. During attack periods PAI-1 levels increased (PAI-1 level of Group 1: 89.6 ng/ml and PAI-1 level of Group 2: 335.7 ng/ml, p = 0.000). Inflammation with increased acute phase reactants continued during both attack and attack-free periods in FMF patients. Prolongation of PT and differences in tPA and P-selectin levels suggest that hypercoagulability may have a role in the etiopathogenesis of FMF. It may be possible to use PAI-1 as a marker for the attacks of FMF.